Originally published as JCO Early Release 10.1200/JCO.2003.02.063 on February 7 2003
Journal of Clinical Oncology, Vol 21, Issue 6
(March), 2003: 976-983
© 2003 American Society for Clinical Oncology
Improved Outcomes From Adding Sequential Paclitaxel but Not From Escalating Doxorubicin Dose in an Adjuvant Chemotherapy Regimen for Patients With Node-Positive Primary Breast Cancer
I. Craig Henderson,
Donald A. Berry,
George D. Demetri,
Constance T. Cirrincione,
Lori J. Goldstein,
Silvana Martino,
James N. Ingle,
M. Robert Cooper,
Daniel F. Hayes,
Katherine H. Tkaczuk,
Gini Fleming,
James F. Holland,
David B. Duggan,
John T. Carpenter,
Emil Frei, III,
Richard L. Schilsky,
William C. Wood,
Hyman B. Muss,
Larry Norton
From the University of California at San Francisco, San, Francisco, CA; Cancer and Leukemia Group B (CALGB) Statistical Center, Durham; Wake Forest University School of Medicine, Winston-Salem, NC; University of Texas M.D. Anderson Cancer, Houston; Southwest Oncology Group Operations, San, Antonio, TX; Dana-Farber Cancer Institute, Boston, MA; Eastern Cooperative Oncology Group Operations, Philadelphia, PA; North Central Cancer Treatment Group Operations, Rochester, MN; Georgetown University Medical Center, Washington, DC; University of Michigan, Ann Arbor, MI; Greenbaum Cancer Center, Baltimore, MD; University of Chicago Medical Center; and CALGB Central Office, Chicago, IL; Mount Sinai School of Medicine; and Memorial Sloan-Kettering Cancer Center, New York; State University of New York Health Science Center at Syracuse, Syracuse, NY; University of Alabama at Birmingham, Birmingham, AL; and University of Vermont, Burlington, VT.
Address reprint requests to I. Craig Henderson, MD, University of California at San Francisco, 1600 Divisadero St, Box 1710, San Francisco, CA 94143; email: craig.henderson{at}accessoncology.com.
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ABSTRACT
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Purpose: This study was designed to determine whether increasing the dose of doxorubicin in or adding paclitaxel to a standard adjuvant chemotherapy regimen for breast cancer patients would prolong time to recurrence and survival.
Patients and Methods: After surgical treatment, 3,121 women with operable breast cancer and involved lymph nodes were randomly assigned to receive a combination of cyclophosphamide (C), 600 mg/m2, with one of three doses of doxorubicin (A), 60, 75, or 90 mg/m2, for four cycles followed by either no further therapy or four cycles of paclitaxel at 175 mg/m2. Tamoxifen was given to 94% of patients with hormone receptor–positive tumors.
Results: There was no evidence of a doxorubicin dose effect. At 5 years, disease-free survival was 69%, 66%, and 67% for patients randomly assigned to 60, 75, and 90 mg/m2, respectively. The hazard reductions from adding paclitaxel to CA were 17% for recurrence (adjusted Wald  2 P = .0023; unadjusted Wilcoxon P = .0011) and 18% for death (adjusted P = .0064; unadjusted P = .0098). At 5 years, the disease-free survival (± SE) was 65% (± 1) and 70% (± 1), and overall survival was 77% (± 1) and 80% (± 1) after CA alone or CA plus paclitaxel, respectively. The effects of adding paclitaxel were not significantly different in subsets defined by the protocol, but in an unplanned subset analysis, the hazard ratio of CA plus paclitaxel versus CA alone was 0.72 (95% confidence interval, 0.59 to 0.86) for those with estrogen receptor–negative tumors and only 0.91 (95% confidence interval, 0.78 to 1.07) for patients with estrogen receptor–positive tumors, almost all of whom received adjuvant tamoxifen. The additional toxicity from adding four cycles of paclitaxel was generally modest.
Conclusion: The addition of four cycles of paclitaxel after the completion of a standard course of CA improves the disease-free and overall survival of patients with early breast cancer.
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INTRODUCTION
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ADJUVANT SYSTEMIC therapy with the drug combination cyclophosphamide, methotrexate, and fluorouracil (CMF) reduces the annual odds of recurrence and death of patients with early breast cancer (± SD) by 24% (± 3%) and 14% (± 4%), respectively.1 An overview of trials in which an anthracycline, either doxorubicin or epirubicin, was added to cyclophosphamide (with or without a vinca alkaloid, methotrexate, or fluorouracil) demonstrated that the anthracycline regimens resulted in a reduction in annual odds (± SD) of 12% (± 4%) and 11% (± 5%) in recurrence or death, respectively, compared with CMF.1 One of the earliest and largest of these studies compared 3 months (four cycles) of cyclophosphamide plus doxorubicin (CA) with 6 months of CMF and failed to show any significant differences in outcome.2 Because the CA regimen used a shorter duration of therapy and was thus perceived as being less toxic, four cycles of CA became one of the most commonly used adjuvant therapy regimens in the United States before the overview that demonstrated the superiority of anthracycline regimens was performed.
The trial reported here was designed to see whether the benefits from four cycles of CA could be increased either by doxorubicin dose escalation or by adding paclitaxel, a drug known to be non–cross-resistant with anthracyclines.3–6 Decreasing the doses of doxorubicin, cyclophosphamide, and fluorouracil below standard levels has been shown to compromise the benefits from adjuvant chemotherapy,7,8 but two studies evaluating cyclophosphamide dose escalation above standard levels have failed to demonstrate additional benefit.9,10 Neither doxorubicin dose escalation nor the use of a taxane has previously been evaluated in the adjuvant setting. To evaluate both questions in one trial, we used a 3 x 2 factorial design.11 Three doxorubicin doses were used to allow for estimating the slope of the dose-response curve and to identify any dose that might skew an estimate of dose effect because it is on a threshold or at a plateau of the dose-response curve. After completion of four cycles of CA, patients were randomly assigned to receive either no further treatment or four cycles of paclitaxel at 3-week intervals.
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PATIENTS AND METHODS
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This was an Intergroup trial (INT 0148) conducted at 516 sites and coordinated by the Cancer and Leukemia Group B (CALGB 9344). Other participants were the Eastern Cooperative Oncology Group, the Southwest Oncology Group, and the North Central Cancer Treatment Group.
Eligible patients had operable breast cancer with clear surgical margins and metastases to axillary nodes. Initial surgical treatment was either mastectomy or lumpectomy with axillary lymph node sampling. Radiotherapy to the breast was required for all patients treated with less than a mastectomy and was begun after all chemotherapy had been administered. The study had to be approved by the institutional review board at each institution enrolling patients, and all patients were required to provide written informed consent before being registered on the study.
Systemic therapy was to have begun within 84 days of the patient’s last surgery. All patients received 600 mg/m2 of cyclophosphamide intravenously on day 1 and were randomly assigned to one of three doxorubicin doses given on day 1 (60 mg/m2) or days 1 and 2 (75 and 90 mg/m2; Fig 1 ). Filgrastim (granulocyte colony-stimulating factor [G-CSF]), 5 µg/kg/d, and ciprofloxacin, 750 mg twice daily, were given routinely to patients receiving 90 mg/m2 of doxorubicin, but only after an episode of febrile neutropenia for other patients. Patients randomly assigned to paclitaxel received 175 mg/m2. Most patients (94%) whose tumor expressed either an estrogen receptor or progesterone receptor received tamoxifen with a recommended duration of 5 years; 21% of patients with receptor-negative tumors also received tamoxifen.
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Fig 1. Protocol schema; 3 x 2 factorial design. After completion of chemotherapy, radiation therapy was administered if patient was treated with lumpectomy or at discretion of physician if patient was treated with masectomy, and tamoxifen 20 mg/d was administered for 5 years if the tumor was receptor positive.
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The National Cancer Institute sponsored this trial and supplied G-CSF, obtained from Amgen Pharmaceuticals (Thousand Oaks, CA), and paclitaxel, obtained from Bristol-Myers Squibb (Princeton, NJ). Subsequent to the completion of the trial, Bristol-Myers Squibb provided a grant to the CALGB for statistical support and to update data for submission to regulatory agencies in the United States and Europe.
Patient Entry and Follow-Up
All patients were evaluated every 3 months during year 1, twice annually for the next 2 years, and annually thereafter. Left ventricular ejection fraction was measured at baseline and again at 5 years. A mammogram and chest x-ray were obtained at entry and then yearly. A bone scan was required before treatment was started, but this requirement was discontinued, consistent with changes in clinical practice, after 2,178 patients had been enrolled.
Complete blood counts were obtained twice weekly, and all toxicities of grade 2 or greater severity were collected on the first 325 patients enrolled onto the trial. Only toxicity of grades 3 or higher was routinely recorded on patients after the Data and Safety Monitoring Board had reviewed toxicity data from the first 325 patients.
Statistical Considerations
The primary end point of this study was duration of disease-free survival. Overall survival and toxicity assessment were secondary end points. Disease-free survival is the interval from study entry to first locoregional recurrence, first distant metastasis, or death as a result of any cause. All patients were observed separately for first local and first distant recurrence, second malignancy, delayed cardiotoxicity, and death.
Patients were randomly assigned at the Statistical Center with equal probability to one of six treatment combinations using a stratified random permuted block design. The number of positive axillary nodes was used as the only stratification factor.
In the primary analysis of disease-free and overall survival, a proportional hazards model was used to assess the main effects of increasing doxorubicin dose (60, 75, and 90 mg/m2), adding paclitaxel (0, 1 [0 is used in the model if the patient did not receive paclitaxel, and 1 is used if the patient did receive paclitaxel]), and the interaction between doxorubicin dose and paclitaxel. Protocol-specified covariates were the number of positive lymph nodes, tumor size, and age. Hazard ratios were obtained from proportional hazards models. Overall hazard ratios were obtained from proportional hazards models. Hazard ratios by year were estimated as the ratio between two groups of the proportion failures observed in time intervals of 1 year in length.
The study was not powered to evaluate effects in subsets. No adjustments in P values have been made for multiple comparisons.
An independent Data and Safety Monitoring Board monitored the study. The protocol used an O’Brien-Fleming rule for early stopping but did not specify rules for reporting results. The original protocol called for analyses after 450, 900, 1,350, and 1,800 events. After the 450th event analysis, the Data and Safety Monitoring Board concluded that patients should be aware of the possible benefits from adding paclitaxel and recommended that the results be released; as a result, the study was first presented at the annual meeting of the American Society of Clinical Oncology in May 1998. This decision was also based on a Bayesian predictive analysis using 1,000 simulations.12 At the time of the 450th event analysis, all patients had been accrued to the study, and every patient had been observed for at least 1 year after random assignment and 6 months after the completion of their protocol-assigned chemotherapy. None of the patients in the trial who were assigned to receive AC only were crossed over to receive paclitaxel subsequent to the results being announced. Bristol-Myers Squibb requested permission to submit the data to the Food and Drug Association (FDA) in support of using paclitaxel as adjuvant treatment for early breast cancer, and in turn, the FDA asked the CALGB to update the database and perform an unplanned analysis after 600 events. An analysis with a median follow-up of 51 months and 900 events was presented to the National Institutes of Health Consensus Conference on Early Breast Cancer in November 2000, and this was the analysis initially submitted to the Journal of Clinical Oncology in February 2002. An updated analysis was undertaken in May 2002 and presented at the 2002 American Society of Clinical Oncology meeting. After discussions with the editors of the Journal of Clinical Oncology, it was decided that the published article should be based on the most up-to-date results, which have a median follow-up of 69 months; this is the analysis reported here. As part of the quality assurance programs of the cooperative groups, randomly chosen patients’ charts were audited on site at least once every 3 years.
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RESULTS
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Between May 1994 and April 1999, 3,121 patients were randomly assigned and began treatment. In the analyses reported here, all of these patients are included in the treatment group to which they were randomly assigned. Median follow-up is 69 months, and three quarters of the patients have been observed for at least 5 years. The characteristics of the patients enrolled are listed in Table 1. There were no significant imbalances in the randomization.
At the time of this analysis, there were 1,054 recurrences (either disease recurrence or death without recurrence) and 742 deaths. There were 343 local recurrences (either isolated or with distant recurrence) and 642 distant recurrences without a local recurrence. Sixty-nine patients died without recurrence.
Efficacy: Doxorubicin Dose
There was no significant reduction in either the hazard of recurrence or death related to doxorubicin dose (Tables 2 and 3). At 5 years, the disease-free survival was 69%, 66%, and 67% for patients randomly assigned to 60, 75, and 90 mg/m2, respectively. Overall survival for these three treatment groups at the same time point was 79%, 79%, and 77%, respectively (Fig 2). The effects of dose are identical, whether all 3,121 patients are included in the analysis or whether only those treated with CA alone or those treated with CA followed by paclitaxel are included (data not shown).
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Fig 2. (A) Disease-free and (B) overall survival of patients randomly assigned to doxorubicin doses of 60, 75, or 90 mg/m2. Adjusted P values from multivariate proportional hazards model, unadjusted P values from the Wilcoxon test (Table 3 ), total number of events, number of patients at risk by year of follow-up, and percentage disease free/alive (± SE) at 6 years are shown.
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Addition of Paclitaxel
Adding paclitaxel to the CA combination led to hazard reductions of 17% for recurrence (adjusted Wald 2 P = .0023) and 18% for death (P = .0064; Table 3). The 1-year probability of recurrence was 7.9% for CA and 4.6% for CA plus paclitaxel, for a relative reduction of 42% attributable to the addition of paclitaxel. This was seen in the first analysis of this study (median follow-up, 21 months) and has not changed significantly with longer follow-up. These early effects are reflected in the Wilcoxon tests for significance (P = .0011 for recurrence and P = .0098 for death). At 5 years, 65% of the patients randomly assigned to CA and 70% assigned to CA plus paclitaxel were alive and free of recurrence, whereas 77% and 80%, respectively, were alive (Fig 3).
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Fig 3. Disease-free (A) and overall survival (B) of patients randomly assigned to cyclophosphamide and doxorubicin alone or with paclitaxel. Adjusted P values from multivariate proportional hazards model, unadjusted P values from the Wilcoxon test (Table 3), total number of events, number of patients at risk, and percentage disease free/alive (± SE) by year of follow-up are shown.
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There was no interaction between doxorubicin dose and the addition of paclitaxel. The addition of a paclitaxel by doxorubicin interaction term to the proportional hazards model did not add predictive information for recurrence (P = .18) or death (P = .20). Each paclitaxel arm performed better than the corresponding CA arm without paclitaxel.
This study was not powered to assess outcomes in patient subsets, but a limited number of subset analyses were performed. In subsets defined by tumor size, number of positive lymph nodes, and patient age, the only covariates specifically mentioned in the protocol, the addition of paclitaxel was consistently beneficial. Although the magnitude of benefit varied, there was no evidence that adding paclitaxel was significantly better for one of these subsets compared with the others. In unplanned subset analyses, two patient subsets showed particular benefit from paclitaxel: patients with negative or unknown tumor receptor status (hazard ratio = 0.72), and patients who did not receive tamoxifen (hazard ratio = 0.69; Table 4). However, the differences between the effects in these subsets were no longer significant after adjusting for multiple comparisons.
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Table 4. Hazard of Recurrence in Patient Subsets Defined by Receptor Status and Use of Tamoxifen: An Unplanned Subset Analysis
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Toxicity
Most patients (98%) who began CA treatment completed all four cycles of therapy, but dose reductions and delays in the initiation of a treatment cycle were significantly more frequent at the higher doxorubicin doses (P < .0001). Severe neutropenia, thrombocytopenia, anemia, blood or platelet transfusions, and hospitalizations increased in frequency with each doxorubicin dose escalation (P < .0001, linear trend in doxorubicin dose). Patients randomly assigned to either of the higher levels of doxorubicin dose were more prone to develop infection than those treated with 60 mg/m2 doxorubicin. Patients randomly assigned to 90 mg/m2 doxorubicin, all of whom routinely received both G-CSF and a prophylactic antibiotic, had about the same frequency of serious infection as those randomly assigned to 75 mg/m2 doxorubicin, who received G-CSF only as needed. Patients on the highest dose had slightly more nausea and vomiting than those on the lower doses, but stomatitis of grade 2, 3, or 4 was dose related (43%, 30%, and 10% of patients randomly assigned to 90, 75, or 60 mg/m2 doxorubicin, respectively; P < .00001, linear trend).
Fifty-eight patients randomly assigned to receive paclitaxel did not receive any; the most common reason was withdrawal of consent (41 of 58 patients). However, 92% of the patients who started paclitaxel completed all four cycles. Paclitaxel treatment resulted in substantially less hematologic toxicity than CA. The percentage of patients with at least one episode of granulocytopenia ( 500/µL) while receiving CA with a doxorubicin dose of 60 mg/m2 was 62%, compared with only 16% during paclitaxel therapy. The incidence of infection requiring an antibiotic was less strikingly different (17% of patients receiving 60 mg/m2 of doxorubicin and 11% of patients receiving paclitaxel). Ten percent of patients on the lowest dose of CA were hospitalized at least once for toxicity, compared with 3% of patients treated with paclitaxel.
Most nonhematologic toxicities were also seen more often and were more severe during treatment with CA than with paclitaxel, including grade II, III, or IV nausea (32% for those receiving the lowest dose of CA v 3% during paclitaxel), vomiting (27% v 1%), and stomatitis (10% v 1%). Hypersensitivity reactions of any severity were seen in 6% of patients during paclitaxel. All but four of these reactions consisted of either urticaria, fever more than 38°C, serum sickness, and/or bronchospasm. Three patients had anaphylaxis, and one patient died of a hypersensitivity reaction. During paclitaxel treatment, 15% of patients had moderate paresthesias, but only 3% had sensory neurotoxicity that interfered with normal functioning. One patient developed a permanent paralysis after one dose of paclitaxel.
Clinically important cardiac dysrhythmias, congestive heart failure, changes in left ventricular ejection fraction, or any other heart symptoms regardless of any possible relationship to treatment occurred in up to 2% of patients during treatment. The incidence of cardiotoxicity during treatment was not significantly different among patients treated with different doxorubicin doses. During posttreatment follow-up, all degrees of cardiotoxicity occurred more often among those randomly assigned to the highest dose of doxorubicin (16%) compared with those treated with 60 (11%) and 75 mg/m2 of doxorubicin (13%; P = .0032, linear trend in doxorubicin dose). There was no difference in incidence of cardiotoxicity between those who did and those who did not receive paclitaxel. Congestive heart failure was observed during active protocol therapy in four (< 1%) and six (< 1%) patients and during posttreatment follow-up in 23 (1%) and 27 (2%) patients randomly assigned to CA alone and CA plus paclitaxel, respectively.
There were no significant differences in the incidences of secondary malignancies, including leukemias and myelodysplasias, on any of the study arms. On the CA-only arms, there were six cases of acute myeloid leukemia, two cases of myelodysplastic disease, and one case of acute lymphoid leukemia. On the AC plus paclitaxel arm, there were four cases of acute myeloid leukemia, four cases of myelodysplastic disease, and no cases of acute lymphoid leukemia.
Three deaths occurred during treatment. A 74-year-old woman died of respiratory and cardiac failure 1 month after her first cycle of CA with doxorubicin 90 mg/m2. Two deaths occurred while patients were receiving paclitaxel. A 49-year-old patient died of a brain infarction 16 days after her third cycle of paclitaxel. The other patient was 74 years old and had an anaphylactic reaction after a paclitaxel infusion of 13 mL during her second cycle.
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DISCUSSION
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Escalation of doxorubicin dose in this trial did not improve either the disease-free or overall survival of patients with stage II breast cancer. However, doxorubicin dose escalation substantially increased hematologic toxicity and stomatitis. There was also a significant monotonic increase in long-term cardiotoxicity by doxorubicin dose.
In contrast, compared with the nonpaclitaxel arms, the paclitaxel arms had a decrease in the hazard of recurrence by 17% (hazard ratio = 0.83, adjusted Wald 2P = .0023) and the hazard of death by 18% (hazard ratio = 0.82, adjusted P = .0064). Hazard reductions seen in years 1 and 2 were significant and have remained so with longer follow-up (this is reflected in the unadjusted Wilcoxon P = .0011 and P = .0098, respectively, for these two end points). The reductions in the hazard of recurrence during year 1 were 41.9%, 41.1%, and 37.4% for the analyses performed after 450, 600, and 900 events. The reductions in hazards during year 2 were 10.7%, 13.6%, and 10.7% for these three analyses, respectively. The absolute difference in 1-year disease-free survival and overall survival between the CA and CA plus paclitaxel arms was 3% and 1%, respectively; the paclitaxel arms had the advantage. An improvement of 5% in disease-free and 3% in overall survival is now evident at 5 years. The benefits from adding paclitaxel to CA observed during the first 5 years should not change at subsequent analyses because 75% of the patients have at least 5 years of follow-up. Whether similar benefits will be observed at longer follow-up intervals (eg, 10 years) cannot be predicted now. The size of the effect from adding paclitaxel to CA is similar to the effect seen from using an anthracycline-containing regimen compared with CMF.1
In subsets defined by nodal status, tumor size, and patient age, the addition of paclitaxel to CA consistently proved advantageous. However, the effect was largest among those whose tumors were hormone-receptor negative and among those who received no adjuvant tamoxifen compared with all other patient subgroups. As these were unplanned subset analyses and not anticipated outcomes, these observations must be interpreted cautiously. Because patients with receptor-positive tumors relapse later than those with receptor-negative tumors, differences in the effectiveness of treatment may diminish with longer follow-up. It would be premature to conclude that these differences in subsets defined by receptor status or tamoxifen use are limited to paclitaxel and not other chemotherapeutic agents. In recent overviews, the benefits from adjuvant chemotherapy were generally smaller in patients with receptor-positive tumors and among those who had received adjuvant tamoxifen.1,13 Few studies in patients with early breast cancer have focused on either receptor status or tamoxifen use as predictive factors for response to adjuvant chemotherapy, but this subset analysis indicates that this should be prospectively evaluated in future trials.
The CA and CA plus paclitaxel arms differed both in duration of therapy (3 v 6 months) and in the drugs used. From this study alone, we cannot determine the individual contribution of each of these factors to the observed outcomes. Three months of CA is standard treatment in the United States because most randomized studies have not shown a clear advantage for longer durations of therapy, and longer durations are associated with an increased likelihood of cardiotoxicity.1,14 However, there are still insufficient data to rule out the possibility that treatment duration is important. An overview of all randomized trials designed to evaluate the importance of treatment duration demonstrated a reduction ± SD of 7% ± 4% (P = .06) in the annual odds of recurrence favoring longer over shorter treatment but no reduction in the annual odds of death.1 Most of the studies in this overview compared treatment durations longer than 6 months. However, in one study that has been recently updated,15 621 premenopausal women with nodal involvement were randomly assigned to either three or six cycles of fluorouracil, epirubicin, and cyclophosphamide.1,15 A significant disease-free and overall survival advantage has emerged for patients receiving the longer treatment duration.
Another potential confounding factor is the possibility that the dose effect was compromised because the higher doses of doxorubicin were administered over 2 days. This seems unlikely because continuous infusions of doxorubicin over 48 to 96 hours seem to be as effective as bolus infusions in patients with metastatic disease,16 but there are no direct comparisons of administering the same dose of doxorubicin over 2 days rather than as a single bolus dose. On the basis of the known pharmacokinetics of doxorubicin, the area under the curve should be the same whether the dose is administered over 1 day or in divided doses.
The original protocol for this study called for a final analysis 4 years after the end of patient accrual. This occurred in April 2001. Times for analyses up to that point were defined by the numbers of events, and the data safety monitoring board used these time points as a guide in announcing the results of the trial. The data safety monitoring board released the results after the first of these analyses, which occurred after 450 events. There have been two updates of the results since that time. The first was in response to a request from the FDA; the time point for this analysis was not data derived. Because of the size of the trial, the importance of the questions for clinical practice in the United States, and the interest in this trial by the oncology community, a fourth analysis was undertaken. This is the analysis reported here. Although there are several widely accepted approaches to making adjustments in statistical significance for multiple analyses taken to determine whether a trial should be stopped early, there is no similar standard for adjusting statistical inference for analyses taken to determine the time for reporting results, and no adjustments have been made.
This is the third large, multicenter, randomized trial that has failed to demonstrate any advantage to breast cancer patients from moderate dose escalation of either cyclophosphamide or doxorubicin with hematopoietic growth factor support for periods of 3 to 4 months.9,10 More extreme dose escalation with stem cell support has similarly failed to improve survival substantially or significantly.17–21 Dose escalation may benefit some breast cancer patients, such as those whose tumors overexpress HER2/neu.22,23 This hypothesis was addressed in this study and will be reported at a later date. At this time, however, there are no data from randomized trials to justify dose escalation of cyclophosphamide beyond 400 mg/m2 and doxorubicin beyond 40 mg/m2.7–10
In this study, the administration of a non–cross-resistant drug, paclitaxel, as a single agent after completion of treatment with a standard therapy, CA, improved disease-free and overall survival. In another study,24 174 patients were randomly assigned to either eight cycles of CA plus fluorouracil or to four cycles of paclitaxel followed by four cycles of CA plus fluorouracil. After a median follow-up of 44 months, there was a 26% reduction in the number of recurrences and a 4% difference in disease-free survival, favoring those treated with paclitaxel, but these differences failed to reach statistical significance in this small study. These two studies taken together still do not rule out the possibility that eight cycles of CA might be as effective as the sequence described here. However, eight cycles of CA using conventional-dose schedules would be considerably more toxic, with unacceptable levels of cardiomyopathy.15 For this reason, we conclude that the use of four cycles of CA followed by four cycles of paclitaxel is a reasonable treatment choice for at least some patients with early breast cancer.
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APPENDIX
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The following institutions participated in the study: Cancer and Leukemia Group B Statistical Center, Durham, NC (Stephen George, PhD; supported by CA33601); Baptist Cancer Institute Community Clinical Oncology Program (CCOP), Memphis, TN (Lee S. Schwartzberg, MD; supported by CA71323); Christiana Care Health Services, Inc, CCOP, Wilmington, DE (Irving M. Berkowitz, DO; supported by CA45418); Community Hospital, Syracuse CCOP, Syracuse, NY (Jeffrey Kirshner, MD; supported by CA45389); Dana-Farber Cancer Institute, Boston, MA (George P Canellos, MD; supported by CA32291); Dartmouth Medical School, Norris Cotton Cancer Center, Lebanon, NH (L. Herbert Maurer, MD; supported by CA04326); Duke University Medical Center, Durham, NC (Jeffrey Crawford, MD; supported by CA47577); Eastern Cooperative Oncology Group, Philadelphia, PA (Robert L. Comis, MD, Chairman; supported by CA21115); Green Mountain Oncology Group CCOP, Bennington, VT (H. James Wallace Jr, MD; supported by CA35091); Kaiser Permanente CCOP, San Diego, CA (Jonathan A. Polikoff, MD; supported by CA45374); Long Island Jewish Medical Center, Lake Success, NY (Marc Citron, MD; supported by CA11028); Massachusetts General Hospital, Boston, MA (Michael L. Grossbard, MD; supported by CA12449); Mount Sinai Medical Center CCOP Miami, Miami Beach, FL (Enrique Davila, MD; supported by CA45564); Mount Sinai School of Medicine, New York, NY (James F. Holland, MD; supported by CA04457); North Central Cancer Treatment Group, Rochester, MN (Michael J O’Connell, MD, Chairman; supported by CA25224); North Shore University Hospital CCOP, Manhasset, NY (Vincent Vinciguerra, MD, supported by CA35279; and Daniel R. Budman, MD, supported by CA35279); Rhode Island Hospital, Providence, RI (Louis A. Leone, MD; supported by CA08025); Roswell Park Cancer Institute, Buffalo, NY (Ellis Levine, MD; supported by CA02599); South New Jersey CCOP, Camden, NJ (Jack Goldberg, MD; supported by CA54697); Southeast Cancer Control Consortium Inc CCOP, Goldsboro, NC (James N. Atkins, MD; supported by CA45808); Southern Nevada Cancer Research Foundation CCOP, Las Vegas, NV (John Ellerton, MD; supported by CA35421); Southwest Oncology Group, San Antonio, TX (Charles Coltman, MD, Chairman; supported by CA31202); St Michael’s Medical Center Tri-County CCOP, Paterson, NJ (Arnold D. Rubin, MD; supported by CA60247); State University of New York Health Science Center at Syracuse, Syracuse, NY (Stephen L. Graziano, MD; supported by CA21060); University of Alabama Birmingham, Birmingham, AL (Robert Diasio, MD; supported by CA47545); University of California at San Diego, San Diego, CA (Stephen L Seagren, MD; supported by CA11789); University of California at San Francisco, San Francisco, CA (Alan P. Venook, MD; supported by CA60138); University of Chicago Medical Center, Chicago, IL (Nicholas J. Vogelzang, MD; supported by CA41287); University of Illinois at Chicago, Chicago, IL (Jeffrey A. Sosman, MD; supported by CA74811); University of Iowa Hospitals, Iowa City, IA (Gerald H. Clamon, MD; supported by CA47642); University of Maryland Cancer Center, Baltimore, MD (David Van Echo, MD; supported by CA31983); University of Massachusetts Medical Center, Worcester, MA (F. Marc Stewart, MD; supported by CA37135); University of Minnesota, Minneapolis, MN (Bruce A. Peterson, MD; supported by CA16450); University of Missouri/Ellis Fischel Cancer Center, Columbia, MO (Michael C. Perry, MD; supported by CA12046); University of Nebraska Medical Center, Omaha, NE (Anne Kessinger, MD; supported by CA77298); University of North Carolina at Chapel Hill, Chapel Hill, NC (Thomas C. Shea, MD; supported by CA47559); University of Tennessee Memphis, Memphis, TN (Harvey B. Niell, MD; supported by CA47555); Vermont Cancer Center, Burlington, VT (Hyman B. Muss, MD; supported by CA77406); Virginia Commonwealth University CCOP, Richmond, VA (John D. Roberts, MD; supported by CA52784); Wake Forest University School of Medicine, Winston-Salem, NC (David D. Hurd, MD; supported by CA03927); Walter Reed Army Medical Center, Washington, DC (John C. Byrd, MD; supported by CA26806); Washington University School of Medicine, St Louis, MO (Nancy L. Bartlett, MD; supported by CA77440); and Weill Medical College of Cornell University, New York, NY (Ted P. Szatrowski, MD; supported by CA07968).
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NOTES
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Supported in part by grant no. CA31946 from the National Cancer Institute, National Institutes of Health, Department of Health and Human Services, Bethesda, MD, to the CALGB (R.L.S.).
The contents of this article are solely the responsibility of the authors and do not necessarily represent the official views of the National Cancer Institute.
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REFERENCES
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1. Early Breast Cancer Trialists Collaborative Group: Polychemotherapy for early breast cancer: An overview of the randomised trials. Early Breast Cancer Trialists’ Collaborative Group. Lancet 352:930–934, 1998[CrossRef][Medline]
2. Fisher B, Brown AM, Dimitrov NV, et al: Two months of doxorubicin-cyclophosphamide with and without interval reinduction therapy compared with 6 months of cyclophosphamide, methotrexate, and fluorouracil in positive-node breast cancer patients with tamoxifen-nonresponsive tumors: Results from National Surgical Adjuvant Breast and Bowel Project B-15. J Clin Oncol 8:1483–1496, 1990[Abstract]
3. Holmes FA, Walters RS, Theriault RL, et al: Phase II trial of Taxol, an active drug in the treatment of metastatic breast cancer. J Natl Cancer Inst 83:1797–1805, 1991[Free Full Text]
4. Seidman AD, Norton L, Reichman BS, et al: Preliminary experience with paclitaxel (Taxol) plus recombinant human granulocyte colony-stimulating factor in the treatment of breast cancer. Semin Oncol 20:40–45, 1993[Medline]
5. Sledge GW, Neuberg D, Ingle J, et al: Phase III trial of doxorubicin (A) vs. paclitaxel (T) vs. doxorubicin + paclitaxel (A+T) as first-line therapy for metastatic breast cancer (MBC): An Intergroup trial. Proc Am Soc Clin Oncol 16:1a, 1997 (abstr 2)
6. Paridaens R, Biganzoli L, Bruning P, et al: Paclitaxel versus doxorubicin as first-line single-agent chemotherapy for metastatic breast cancer: A European Organization for Research and Treatment of Cancer randomized study with cross-over. J Clin Oncol 18:724–733, 2000[Abstract/Free Full Text]
7. Wood WC, Budman DR, Korzun AH, et al: Dose and dose intensity of adjuvant chemotherapy for stage II, node-positive breast carcinoma. N Engl J Med 330:1253–1259, 1994[Abstract/Free Full Text]
8. Budman DR, Berry DA, Cirrincione CT, et al: Dose and dose intensity as determinants of outcome in the adjuvant treatment of breast cancer: The Cancer and Leukemia Group B. J Natl Cancer Inst 90:1205–1211, 1998[Abstract/Free Full Text]
9. Fisher B, Anderson S, Wickerham DL, et al: Increased intensification and total dose of cyclophosphamide in a doxorubicin-cyclophosphamide regimen for the treatment of primary breast cancer: Findings from National Surgical Adjuvant Breast and Bowel Project B-22. J Clin Oncol 15:1858–1869, 1997[Abstract/Free Full Text]
10. Fisher B, Anderson S, DeCillis A, et al: Further evaluation of intensified and increased total dose of cyclophosphamide for the treatment of primary breast cancer: Findings from national surgical adjuvant breast and bowel project B-25. J Clin Oncol 17:3374–3388, 1999[Abstract/Free Full Text]
11. Box GEP, Hunter WG, Hunter JS: Statistics for experimenters: An introduction to design, data analysis, and model building. New York, NY, Wiley, 1978
12. DeGroot MH: Probability and Statistics (ed 2). Reading, MA, Addison-Wesley, 1987
13. Coates AS, Gelber RD, Goldhirsch A: Subsets within the chemotherapy overview. International Breast Cancer Study Group. Lancet 352:1783–1784, 1998 (letter)[Medline]
14. Shapiro CL, Hardenbergh PH, Gelman R, et al: Cardiac effects of adjuvant doxorubicin and radiation therapy in breast cancer patients. J Clin Oncol 16:3493–3501, 1998[Abstract]
15. Fumoleau P, Brémond A, Kerbrat P, et al: Better outcome of premenopausal node-positive (N+) breast cancer patients (pts) treated with 6 cycles vs 3 cycles of adjuvant chemotherapy: Eight year follow-up results of FASG 01. Proc Am Soc Clin Oncol 18:67a, 1999 (abstr 252)
16. Legha SS, Benjamin RS, Mackay B, et al: Reduction of doxorubicin cardiotoxicity by prolonged continuous intravenous infusion. Ann Intern Med 96:133–139, 1982[CrossRef][Medline]
17. Hortobagyi GN, Buzdar AU, Theriault RL, et al: Randomized trial of high-dose chemotherapy and blood cell autografts for high-risk primary breast carcinoma. J Natl Cancer Inst 92:225–233, 2000[Abstract/Free Full Text]
18. Rodenhuis S, Richel DJ, van der Wall E, et al: Randomised trial of high-dose chemotherapy and haematopoietic progenitor-cell support in operable breast cancer with extensive axillary lymph-node involvement. Lancet 352:515–521, 1998[CrossRef][Medline]
19. Bergh J, Wiklund T, Erikstein B, et al: Tailored fluorouracil, epirubicin, and cyclophosphamide compared with marrow-supported high-dose chemotherapy as adjuvant treatment for high-risk breast cancer: A randomised trial. Scandinavian Breast Group 9401 study. Lancet 356:1384–1391, 2000[CrossRef][Medline]
20. Peters W, Rosner G, Vredenburgh J, et al: A prospective, randomized comparison of two doses of combination alkylating agents (AA) as consolidation after CAF in high-risk primary breast cancer involving ten or more axillary lymph nodes (LN): Preliminary results of CALGB 9082/SWOG9114/NCIC MA-13. Proc Am Soc Clin Oncol 18:1a, 1999 (abstr 2)
21. Rodenhuis S, Bontenbal M, Beex LVAM, et al: Randomized phase III study of high-dose chemotherapy with cyclophosphamide, thiotepa and carboplatin in operable breast cancer with 4 or more axillary lymph nodes. Proc Am Soc Clin Oncol 19:74a, 2000 (abstr 286)
22. Muss HB, Thor A, Berry DA, et al: c-erbB-2 expression and response to adjuvant therapy in women with node-positive early breast cancer. N Engl J Med 330:1260–1266, 1994[Abstract/Free Full Text]
23. Thor AD, Berry DA, Budman DR, et al: erbB-2, p53, and efficacy of adjuvant therapy in lymph node-positive breast cancer. J Natl Cancer Inst 90:1346–1360, 1998[Abstract/Free Full Text]
24. Buzdar AU, Singletary SE, Valero V, et al: Evaluation of paclitaxel in adjuvant chemotherapy for patients with operable breast cancer: Preliminary data of a prospective randomized trial. Clin Cancer Res 8:1073–1079, 2002[Abstract/Free Full Text]
Submitted February 12, 2002;
accepted October 23, 2002.
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R. Tubbs, W. E. Barlow, G. T. Budd, E. Swain, P. Porter, A. Gown, I-T. Yeh, G. Sledge, C. Shapiro, J. Ingle, et al.
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[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
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2938 - 2945.
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[Full Text]
[PDF]
|
|
|
|
|
|
|
L. Gianni, J. Baselga, W. Eiermann, V. G. Porta, V. Semiglazov, A. Lluch, M. Zambetti, D. Sabadell, G. Raab, A. L. Cussac, et al.
Phase III Trial Evaluating the Addition of Paclitaxel to Doxorubicin Followed by Cyclophosphamide, Methotrexate, and Fluorouracil, As Adjuvant or Primary Systemic Therapy: European Cooperative Trial in Operable Breast Cancer
J. Clin. Oncol.,
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27(15):
2474 - 2481.
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[Full Text]
[PDF]
|
|
|
|
|
|
|
R. A. Miksad, M. Gonen, T. J. Lynch, and T. G. Roberts Jr
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J. Clin. Oncol.,
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27(13):
2245 - 2252.
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[Full Text]
[PDF]
|
|
|
|
|
|
|
H. K. Chew, J. H. Doroshow, P. Frankel, K. A. Margolin, G. Somlo, H.-J. Lenz, M. Gordon, W. Zhang, D. Yang, C. Russell, et al.
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May 1, 2009;
27(13):
2163 - 2169.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
T. ISHIKAWA, S. SHIMIZU, K. KATAYAMA, T. CHISHIMA, Y. HAMAGUCHI, T. DOI, M. TANABE, A. KASAHARA, N. YAMAGUCHI, K. NARUI, et al.
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May 1, 2009;
29(5):
1515 - 1520.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
E. L. Korn, B. Freidlin, and M. Mooney
Stopping or Reporting Early for Positive Results in Randomized Clinical Trials: The National Cancer Institute Cooperative Group Experience From 1990 to 2005
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April 1, 2009;
27(10):
1712 - 1721.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Jones, F. A. Holmes, J. O'Shaughnessy, J. L. Blum, S. J. Vukelja, K. J. McIntyre, J. E. Pippen, J. H. Bordelon, R. L. Kirby, J. Sandbach, et al.
Docetaxel With Cyclophosphamide Is Associated With an Overall Survival Benefit Compared With Doxorubicin and Cyclophosphamide: 7-Year Follow-Up of US Oncology Research Trial 9735
J. Clin. Oncol.,
March 10, 2009;
27(8):
1177 - 1183.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
L. Gianni and P. Valagussa
Anthracyclines and Early Breast Cancer: The End of an Era?
J. Clin. Oncol.,
March 10, 2009;
27(8):
1155 - 1157.
[Full Text]
[PDF]
|
|
|
|
|
|
|
E. de Azambuja, M. Paesmans, M. Beauduin, A. Vindevoghel, N. Cornez, C. Finet, F. Ries, M. T. Closon-Dejardin, J. Kerger, P. Gobert, et al.
Long-Term Benefit of High-Dose Epirubicin in Adjuvant Chemotherapy for Node-Positive Breast Cancer: 15-Year Efficacy Results of the Belgian Multicentre Study
J. Clin. Oncol.,
February 10, 2009;
27(5):
720 - 725.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
P. G. Morris, H. L. McArthur, C. T. Dang, and C. A. Hudis
Selection of Appropriate Patients for Anthracycline Therapy
ASCO Educational Book,
January 1, 2009;
2009(1):
11 - 18.
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|
|
|
|
|
|
|
D. J. Lenihan and F. J. Esteva
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December 1, 2008;
13(12):
1224 - 1234.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
G. Somlo, P. Chu, P. Frankel, W. Ye, S. Groshen, J. H. Doroshow, K. Danenberg, and P. Danenberg
Molecular profiling including epidermal growth factor receptor and p21 expression in high-risk breast cancer patients as indicators of outcome
Ann. Onc.,
November 1, 2008;
19(11):
1853 - 1859.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. Berruti, M. P. Brizzi, D. Generali, M. Ardine, L. Dogliotti, P. Bruzzi, and A. Bottini
Presurgical Systemic Treatment of Nonmetastatic Breast Cancer: Facts and Open Questions
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November 1, 2008;
13(11):
1137 - 1148.
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|
|
|
|
|
|
|
H. W Tuffaha, I. M Treish, and L. Zaru
The use and effectiveness of granulocyte colony-stimulating factor in primary prophylaxis for febrile neutropenia in the outpatient setting
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September 1, 2008;
14(3):
131 - 138.
[Abstract]
[PDF]
|
|
|
|
|
|
|
L. J. Goldstein, R. Gray, S. Badve, B. H. Childs, C. Yoshizawa, S. Rowley, S. Shak, F. L. Baehner, P. M. Ravdin, N. E. Davidson, et al.
Prognostic Utility of the 21-Gene Assay in Hormone Receptor-Positive Operable Breast Cancer Compared With Classical Clinicopathologic Features
J. Clin. Oncol.,
September 1, 2008;
26(25):
4063 - 4071.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
L. J. Goldstein, A. O'Neill, J. A. Sparano, E. A. Perez, L. N. Shulman, S. Martino, and N. E. Davidson
Concurrent Doxorubicin Plus Docetaxel Is Not More Effective Than Concurrent Doxorubicin Plus Cyclophosphamide in Operable Breast Cancer With 0 to 3 Positive Axillary Nodes: North American Breast Cancer Intergroup Trial E 2197
J. Clin. Oncol.,
September 1, 2008;
26(25):
4092 - 4099.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. A. Cannistra
Challenges and Pitfalls of Combining Targeted Agents in Phase I Studies
J. Clin. Oncol.,
August 1, 2008;
26(22):
3665 - 3667.
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. Dang, L. Norton, and C. Hudis
Dose-Dense Chemotherapy With Trastuzumab Is an Appropriate Option
J. Clin. Oncol.,
July 20, 2008;
26(21):
3655 - 3656.
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. Peppercorn and A. H. Partridge
Breast Cancer in Young Women: A New Color or a Different Shade of Pink?
J. Clin. Oncol.,
July 10, 2008;
26(20):
3303 - 3305.
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Martin, A. Rodriguez-Lescure, A. Ruiz, E. Alba, L. Calvo, M. Ruiz-Borrego, B. Munarriz, C. A. Rodriguez, C. Crespo, E. de Alava, et al.
Randomized Phase 3 Trial of Fluorouracil, Epirubicin, and Cyclophosphamide Alone or Followed by Paclitaxel for Early Breast Cancer
J Natl Cancer Inst,
June 4, 2008;
100(11):
805 - 814.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. Hudis and C. Dang
The Taxane Limbo: How Low Can We Go?
J Natl Cancer Inst,
June 4, 2008;
100(11):
761 - 763.
[Full Text]
[PDF]
|
|
|
|
|
|
|
G. Fountzilas, U. Dafni, H. Gogas, H. Linardou, H. P. Kalofonos, E. Briasoulis, D. Pectasides, E. Samantas, D. Bafaloukos, G. P. Stathopoulos, et al.
Postoperative dose-dense sequential chemotherapy with epirubicin, paclitaxel and CMF in patients with high-risk breast cancer: safety analysis of the Hellenic Cooperative Oncology Group randomized phase III trial HE 10/00
Ann. Onc.,
May 1, 2008;
19(5):
853 - 860.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. A. Sparano, M. Wang, S. Martino, V. Jones, E. A. Perez, T. Saphner, A. C. Wolff, G. W. Sledge Jr., W. C. Wood, and N. E. Davidson
Weekly Paclitaxel in the Adjuvant Treatment of Breast Cancer
N. Engl. J. Med.,
April 17, 2008;
358(16):
1663 - 1671.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
P. Maruvada and S. Srivastava
Joint National Cancer Institute-Food and Drug Administration Workshop on Research Strategies, Study Designs, and Statistical Approaches to Biomarker Validation for Cancer Diagnosis and Detection
Am. Assoc. Cancer Res. Educ. Book,
April 12, 2008;
2008(1):
239 - 247.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Puhalla, E. Mrozek, D. Young, S. Ottman, A. McVey, K. Kendra, N. J. Merriman, M. Knapp, T. Patel, M. E. Thompson, et al.
Randomized Phase II Adjuvant Trial of Dose-Dense Docetaxel Before or After Doxorubicin Plus Cyclophosphamide in Axillary Node-Positive Breast Cancer
J. Clin. Oncol.,
April 1, 2008;
26(10):
1691 - 1697.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. Dang, M. Fornier, S. Sugarman, T. Troso-Sandoval, D. Lake, G. D'Andrea, A. Seidman, N. Sklarin, M. Dickler, V. Currie, et al.
The Safety of Dose-Dense Doxorubicin and Cyclophosphamide Followed by Paclitaxel With Trastuzumab in HER-2/neu Overexpressed/Amplified Breast Cancer
J. Clin. Oncol.,
March 10, 2008;
26(8):
1216 - 1222.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
E. A. Perez, V. J. Suman, N. E. Davidson, G. W. Sledge, P. A. Kaufman, C. A. Hudis, S. Martino, J. R. Gralow, S. R. Dakhil, J. N. Ingle, et al.
Cardiac Safety Analysis of Doxorubicin and Cyclophosphamide Followed by Paclitaxel With or Without Trastuzumab in the North Central Cancer Treatment Group N9831 Adjuvant Breast Cancer Trial
J. Clin. Oncol.,
March 10, 2008;
26(8):
1231 - 1238.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
L.-P. P. Tran and J. L. Grabinski
Chemotherapy for Early-Stage Breast Cancer: A Paradigm in Flux
Journal of Pharmacy Practice,
February 1, 2008;
21(1):
46 - 56.
[Abstract]
[PDF]
|
|
|
|
|
|
|
L. Del Mastro, B. Dozin, E. Aitini, T. Catzeddu, E. Baldini, A. Contu, A. Durando, S. Danese, G. Cavazzini, G. Canavese, et al.
Timing of adjuvant chemotherapy and tamoxifen in women with breast cancer: findings from two consecutive trials of Gruppo Oncologico Nord-Ovest-Mammella Intergruppo (GONO-MIG) Group
Ann. Onc.,
February 1, 2008;
19(2):
299 - 307.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. De Laurentiis, G. Cancello, D. D'Agostino, M. Giuliano, A. Giordano, E. Montagna, R. Lauria, V. Forestieri, A. Esposito, L. Silvestro, et al.
Taxane-Based Combinations As Adjuvant Chemotherapy of Early Breast Cancer: A Meta-Analysis of Randomized Trials
J. Clin. Oncol.,
January 1, 2008;
26(1):
44 - 53.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. E. Cazzaniga, G. Mustacchi, P. Pronzato, A. De Matteis, F. Di Costanzo, I. Floriani, and On behalf of the NORA Study Group
Adjuvant treatment of early breast cancer: do the St Gallen recommendations influence clinical practice? Results from the NORA study
Ann. Onc.,
December 1, 2007;
18(12):
1976 - 1980.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
D. F. Hayes, A. D. Thor, L. G. Dressler, D. Weaver, S. Edgerton, D. Cowan, G. Broadwater, L. J. Goldstein, S. Martino, J. N. Ingle, et al.
HER2 and Response to Paclitaxel in Node-Positive Breast Cancer
N. Engl. J. Med.,
October 11, 2007;
357(15):
1496 - 1506.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. Moore
Breast-Cancer Therapy -- Looking Back to the Future
N. Engl. J. Med.,
October 11, 2007;
357(15):
1547 - 1549.
[Full Text]
[PDF]
|
|
|
|
|
|
|
H. B. Muss, D. A. Berry, C. Cirrincione, D. R. Budman, I. C. Henderson, M. L. Citron, L. Norton, E. P. Winer, and C. A. Hudis
Toxicity of Older and Younger Patients Treated With Adjuvant Chemotherapy for Node-Positive Breast Cancer: The Cancer and Leukemia Group B Experience
J. Clin. Oncol.,
August 20, 2007;
25(24):
3699 - 3704.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
N. Denduluri, J. A. Low, J. J. Lee, A. W. Berman, J. M. Walshe, U. Vatas, C. K. Chow, S. M. Steinberg, S. X. Yang, and S. M. Swain
Phase II Trial of Ixabepilone, an Epothilone B Analog, in Patients With Metastatic Breast Cancer Previously Untreated With Taxanes
J. Clin. Oncol.,
August 10, 2007;
25(23):
3421 - 3427.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. M. Gonzalez-Angulo, B. T. Hennessy, K. Broglio, F. Meric-Bernstam, M. Cristofanilli, S. H. Giordano, T. A. Buchholz, A. Sahin, S. E. Singletary, A. U. Buzdar, et al.
Trends for Inflammatory Breast Cancer: Is Survival Improving?
Oncologist,
August 1, 2007;
12(8):
904 - 912.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. M. Layman, D. G. Thomas, K. A. Griffith, J. B. Smerage, M. A. Helvie, M. A. Roubidoux, K. M. Diehl, L. A. Newman, M. S. Sabel, J. A. Hayman, et al.
Neoadjuvant Docetaxel and Capecitabine and the Use of Thymidine Phosphorylase as a Predictive Biomarker in Breast Cancer
Clin. Cancer Res.,
July 15, 2007;
13(14):
4092 - 4097.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Verma and M. Clemons
First-Line Treatment Options for Patients with HER-2 Negative Metastatic Breast Cancer: The Impact of Modern Adjuvant Chemotherapy
Oncologist,
July 1, 2007;
12(7):
785 - 797.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
N. L. Henry and D. F. Hayes
Can Biology Trump Anatomy? Do All Node-Positive Patients With Breast Cancer Need Chemotherapy?
J. Clin. Oncol.,
June 20, 2007;
25(18):
2501 - 2503.
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Sui, Y. Huang, B. H. Park, N. E. Davidson, and W. Fan
Estrogen Receptor {alpha} Mediates Breast Cancer Cell Resistance to Paclitaxel through Inhibition of Apoptotic Cell Death
Cancer Res.,
June 1, 2007;
67(11):
5337 - 5344.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
H. C.F. Moore, S. J. Green, J. R. Gralow, S. I. Bearman, D. Lew, W. E. Barlow, C. Hudis, A. C. Wolff, J. N. Ingle, H. K. Chew, et al.
Intensive Dose-Dense Compared With High-Dose Adjuvant Chemotherapy for High-Risk Operable Breast Cancer: Southwest Oncology Group/Intergroup Study 9623
J. Clin. Oncol.,
May 1, 2007;
25(13):
1677 - 1682.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. U. Buzdar
Adjuvant Chemotherapy for High-Risk Operable Breast Cancer
J. Clin. Oncol.,
May 1, 2007;
25(13):
1642 - 1644.
[Full Text]
[PDF]
|
|
|
|
|
|
|
The Adjuvant Breast Cancer Trials Collaborative Gr
Polychemotherapy for Early Breast Cancer: Results From the International Adjuvant Breast Cancer Chemotherapy Randomized Trial
J Natl Cancer Inst,
April 4, 2007;
99(7):
506 - 515.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
N Wilking, E Lidbrink, T Wiklund, B Erikstein, H Lindman, P Malmstrom, P Kellokumpu-Lehtinen, N-O Bengtsson, G Soderlund, G Anker, et al.
Long-term follow-up of the SBG 9401 study comparing tailored FEC-based therapy versus marrow-supported high-dose therapy
Ann. Onc.,
April 1, 2007;
18(4):
694 - 700.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Buchholz, A. V. Schally, J. B. Engel, F. Hohla, E. Heinrich, F. Koester, J. L. Varga, and G. Halmos
Potentiation of mammary cancer inhibition by combination of antagonists of growth hormone-releasing hormone with docetaxel
PNAS,
February 6, 2007;
104(6):
1943 - 1946.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
P Piedbois, D Serin, F Priou, P Laplaige, S Greget, E Angellier, E Teissier, J-F Berdah, M Fabbro, B Valenza, et al.
Dose-dense adjuvant chemotherapy in node-positive breast cancer: docetaxel followed by epirubicin/cyclophosphamide (T/EC), or the reverse sequence (EC/T), every 2 weeks, versus docetaxel, epirubicin and cyclophosphamide (TEC) every 3 weeks. AERO B03 randomized phase II study
Ann. Onc.,
January 1, 2007;
18(1):
52 - 57.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. T. Chlebowski, G. L. Blackburn, C. A. Thomson, D. W. Nixon, A. Shapiro, M. K. Hoy, M. T. Goodman, A. E. Giuliano, N. Karanja, P. McAndrew, et al.
Dietary Fat Reduction and Breast Cancer Outcome: Interim Efficacy Results From the Women's Intervention Nutrition Study
J Natl Cancer Inst,
December 20, 2006;
98(24):
1767 - 1776.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
H. Roche, P. Fumoleau, M. Spielmann, J.-L. Canon, T. Delozier, D. Serin, M. Symann, P. Kerbrat, P. Soulie, F. Eichler, et al.
Sequential Adjuvant Epirubicin-Based and Docetaxel Chemotherapy for Node-Positive Breast Cancer Patients: The FNCLCC PACS 01 Trial
J. Clin. Oncol.,
December 20, 2006;
24(36):
5664 - 5671.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. M. Walshe, N. Denduluri, and S. M. Swain
Amenorrhea in Premenopausal Women After Adjuvant Chemotherapy for Breast Cancer
J. Clin. Oncol.,
December 20, 2006;
24(36):
5769 - 5779.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. E. Jones, M. A. Savin, F. A. Holmes, J. A. O'Shaughnessy, J. L. Blum, S. Vukelja, K. J. McIntyre, J. E. Pippen, J. H. Bordelon, R. Kirby, et al.
Phase III Trial Comparing Doxorubicin Plus Cyclophosphamide With Docetaxel Plus Cyclophosphamide As Adjuvant Therapy for Operable Breast Cancer
J. Clin. Oncol.,
December 1, 2006;
24(34):
5381 - 5387.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. N. Levine and T. Whelan
Adjuvant Chemotherapy for Breast Cancer -- 30 Years Later
N. Engl. J. Med.,
November 2, 2006;
355(18):
1920 - 1922.
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. Lohrisch, C. Paltiel, K. Gelmon, C. Speers, S. Taylor, J. Barnett, and I. A. Olivotto
Impact on Survival of Time From Definitive Surgery to Initiation of Adjuvant Chemotherapy for Early-Stage Breast Cancer
J. Clin. Oncol.,
October 20, 2006;
24(30):
4888 - 4894.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
D. A. Berry, L. Inoue, Y. Shen, J. Venier, D. Cohen, M. Bondy, R. Theriault, and M. F. Munsell
Chapter 6: Modeling the Impact of Treatment and Screening on U.S. Breast Cancer Mortality: A Bayesian Approach
J Natl Cancer Inst Monographs,
October 1, 2006;
2006(36):
30 - 36.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
E. B. Lamont, J. E. Herndon II, J. C. Weeks, I. C. Henderson, C. C. Earle, R. L. Schilsky, and N. A. Christakis
Measuring disease-free survival and cancer relapse using Medicare claims from CALGB breast cancer trial participants (companion to 9344).
J Natl Cancer Inst,
September 20, 2006;
98(18):
1335 - 1338.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
W. P. McGuire
Is it time for some new approaches for treating advanced ovarian cancer?
J Natl Cancer Inst,
August 2, 2006;
98(15):
1024 - 1026.
[Full Text]
[PDF]
|
|
|
|
|
|
|
P. S. Hupperets and V. C. Tjan-Heijnen
Primary or secondary G-CSF prophylaxis to support TAC chemotherapy in breast cancer?
Ann. Onc.,
August 1, 2006;
17(8):
1181 - 1183.
[Full Text]
[PDF]
|
|
|
|
|
|
|
T. J. Smith, J. Khatcheressian, G. H. Lyman, H. Ozer, J. O. Armitage, L. Balducci, C. L. Bennett, S. B. Cantor, J. Crawford, S. J. Cross, et al.
2006 Update of Recommendations for the Use of White Blood Cell Growth Factors: An Evidence-Based Clinical Practice Guideline
J. Clin. Oncol.,
July 1, 2006;
24(19):
3187 - 3205.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
E. B. Elkin, A. Hurria, N. Mitra, D. Schrag, and K. S. Panageas
Adjuvant Chemotherapy and Survival in Older Women With Hormone Receptor-Negative Breast Cancer: Assessing Outcome in a Population-Based, Observational Cohort
J. Clin. Oncol.,
June 20, 2006;
24(18):
2757 - 2764.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
P. Maruvada and S. Srivastava
Joint national cancer institute-food and drug administration workshop on research strategies, study designs, and statistical approaches to biomarker validation for cancer diagnosis and detection.
Cancer Epidemiol. Biomarkers Prev.,
June 1, 2006;
15(6):
1078 - 1082.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Tanner, J. Isola, T. Wiklund, B. Erikstein, P. Kellokumpu-Lehtinen, P. Malmstrom, N. Wilking, J. Nilsson, and J. Bergh
Topoisomerase II{alpha} Gene Amplification Predicts Favorable Treatment Response to Tailored and Dose-Escalated Anthracycline-Based Adjuvant Chemotherapy in HER-2/neu-Amplified Breast Cancer: Scandinavian Breast Group Trial 9401
J. Clin. Oncol.,
June 1, 2006;
24(16):
2428 - 2436.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. A. Bogart, S. L. Seagren, and A. Glicksman
Radiation oncology research in the cancer and leukemia group B.
Clin. Cancer Res.,
June 1, 2006;
12(11):
3628s - 3634s.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. K. Plevritis, A. W. Kurian, B. M. Sigal, B. L. Daniel, D. M. Ikeda, F. E. Stockdale, and A. M. Garber
Cost-effectiveness of screening BRCA1/2 mutation carriers with breast magnetic resonance imaging.
JAMA,
May 24, 2006;
295(20):
2374 - 2384.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
E. O. Hanrahan, V. Valero, A. M. Gonzalez-Angulo, and G. N. Hortobagyi
Prognosis and Management of Patients With Node-Negative Invasive Breast Carcinoma That Is 1 cm or Smaller in Size (stage 1; T1a,bN0M0): A Review of the Literature
J. Clin. Oncol.,
May 1, 2006;
24(13):
2113 - 2122.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
H. D. Bear, S. Anderson, R. E. Smith, C. E. Geyer Jr, E. P. Mamounas, B. Fisher, A. M. Brown, A. Robidoux, R. Margolese, M. S. Kahlenberg, et al.
Sequential Preoperative or Postoperative Docetaxel Added to Preoperative Doxorubicin Plus Cyclophosphamide for Operable Breast Cancer: National Surgical Adjuvant Breast and Bowel Project Protocol B-27
J. Clin. Oncol.,
May 1, 2006;
24(13):
2019 - 2027.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
D. A. Berry, C. Cirrincione, I. C. Henderson, M. L. Citron, D. R. Budman, L. J. Goldstein, S. Martino, E. A. Perez, H. B. Muss, L. Norton, et al.
Estrogen-Receptor Status and Outcomes of Modern Chemotherapy for Patients With Node-Positive Breast Cancer
JAMA,
April 12, 2006;
295(14):
1658 - 1667.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Woloshin and L. M. Schwartz
What's the rush? The dissemination and adoption of preliminary research results.
J Natl Cancer Inst,
March 15, 2006;
98(6):
372 - 373.
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. H. Giordano, Z. Duan, Y.-F. Kuo, G. N. Hortobagyi, J. Freeman, and J. S. Goodwin
Impact of a scientific presentation on community treatment patterns for primary breast cancer.
J Natl Cancer Inst,
March 15, 2006;
98(6):
382 - 388.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. B. Chakravarthy, M. C. Kelley, B. McLaren, C. I. Truica, D. Billheimer, I. A. Mayer, A. M. Grau, D. H. Johnson, J. F. Simpson, R. D. Beauchamp, et al.
Neoadjuvant Concurrent Paclitaxel and Radiation in Stage II/III Breast Cancer
Clin. Cancer Res.,
March 1, 2006;
12(5):
1570 - 1576.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Colozza, E. de Azambuja, F. Cardoso, C. Bernard, and M. J. Piccart
Breast cancer: achievements in adjuvant systemic therapies in the pre-genomic era.
Oncologist,
February 1, 2006;
11(2):
111 - 125.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
I. Smith and S. Chua
Medical treatment of early breast cancer. III: chemotherapy
BMJ,
January 21, 2006;
332(7534):
161 - 162.
[Full Text]
[PDF]
|
|
|
|
|
|
|
L. Gianni, J. Baselga, W. Eiermann, V. Guillem Porta, V. Semiglazov, A. Lluch, M. Zambetti, D. Sabadell, G. Raab, A. Llombart Cussac, et al.
Feasibility and Tolerability of Sequential Doxorubicin/Paclitaxel Followed by Cyclophosphamide, Methotrexate, and Fluorouracil and Its Effects on Tumor Response as Preoperative Therapy
Clin. Cancer Res.,
December 15, 2005;
11(24):
8715 - 8721.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Venturini, L. Del Mastro, E. Aitini, E. Baldini, C. Caroti, A. Contu, F. Testore, F. Brema, P. Pronzato, G. Cavazzini, et al.
Dose-Dense Adjuvant Chemotherapy in Early Breast Cancer Patients: Results From a Randomized Trial
J Natl Cancer Inst,
December 7, 2005;
97(23):
1724 - 1733.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
B. K Moser and S. L George
A general formulation for a one-sided group sequential design
Clinical Trials,
December 1, 2005;
2(6):
519 - 528.
[Abstract]
[PDF]
|
|
|
|
|
|
|
T. J Smith and J. Khatcheressian
Review: chemotherapy and hormonal therapy reduce recurrence and mortality at 15 years in early breast cancer
Evid. Based Med.,
December 1, 2005;
10(6):
169 - 169.
[Full Text]
[PDF]
|
|
|
|
|
|
|
L. F. Hutchins, S. J. Green, P. M. Ravdin, D. Lew, S. Martino, M. Abeloff, A. P. Lyss, C. Allred, S. E. Rivkin, and C. K. Osborne
Randomized, Controlled Trial of Cyclophosphamide, Methotrexate, and Fluorouracil Versus Cyclophosphamide, Doxorubicin, and Fluorouracil With and Without Tamoxifen for High-Risk, Node-Negative Breast Cancer: Treatment Results of Intergroup Protocol INT-0102
J. Clin. Oncol.,
November 20, 2005;
23(33):
8313 - 8321.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. E. Langley, J. Carmichael, A. L. Jones, D. A. Cameron, W. Qian, B. Uscinska, A. Howell, and M. Parmar
Phase III Trial of Epirubicin Plus Paclitaxel Compared With Epirubicin Plus Cyclophosphamide As First-Line Chemotherapy for Metastatic Breast Cancer: United Kingdom National Cancer Research Institute Trial AB01
J. Clin. Oncol.,
November 20, 2005;
23(33):
8322 - 8330.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
H. J. Burstein, L. M. Parker, A. Keshaviah, J. Doherty, A. H. Partridge, L. Schapira, P. D. Ryan, J. Younger, L. N. Harris, B. Moy, et al.
Efficacy of Pegfilgrastim and Darbepoetin Alfa As Hematopoietic Support for Dose-Dense Every-2-Week Adjuvant Breast Cancer Chemotherapy
J. Clin. Oncol.,
November 20, 2005;
23(33):
8340 - 8347.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Harries, P. Ellis, and P. Harper
Nanoparticle Albumin-Bound Paclitaxel for Metastatic Breast Cancer
J. Clin. Oncol.,
November 1, 2005;
23(31):
7768 - 7771.
[Full Text]
[PDF]
|
|
|
|
|
|
|
G. Fountzilas, D. Skarlos, U. Dafni, H. Gogas, E. Briasoulis, D. Pectasides, C. Papadimitriou, C. Markopoulos, A. Polychronis, H. P. Kalofonos, et al.
Postoperative dose-dense sequential chemotherapy with epirubicin, followed by CMF with or without paclitaxel, in patients with high-risk operable breast cancer: a randomized phase III study conducted by the Hellenic Cooperative Oncology Group
Ann. Onc.,
November 1, 2005;
16(11):
1762 - 1771.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Gluck
Adjuvant Chemotherapy for Early Breast Cancer: Optimal Use of Epirubicin
Oncologist,
November 1, 2005;
10(10):
780 - 791.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
E. P. Mamounas
Can We Approach Zero Relapse in Breast Cancer?
Oncologist,
October 1, 2005;
10(suppl_2):
9 - 17.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. C. Green, A. U. Buzdar, T. Smith, N. K. Ibrahim, V. Valero, M. F. Rosales, M. Cristofanilli, D. J. Booser, L. Pusztai, E. Rivera, et al.
Weekly Paclitaxel Improves Pathologic Complete Remission in Operable Breast Cancer When Compared With Paclitaxel Once Every 3 Weeks
J. Clin. Oncol.,
September 1, 2005;
23(25):
5983 - 5992.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
D. A. Stewart, A. H. G. Paterson, J. D. Ruether, J. Russell, P. Craighead, M. Smylie, and J. Mackey
High-dose mitoxantrone-vinblastine-cyclophosphamide and autologous stem cell transplantation for stage III breast cancer: final results of a prospective multicentre study
Ann. Onc.,
September 1, 2005;
16(9):
1463 - 1468.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. Hudis
Testing Chemotherapy for Breast Cancer: Timing Is Everything
J. Clin. Oncol.,
August 20, 2005;
23(24):
5434 - 5436.
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. N. Levine, K. I. Pritchard, V. H.C. Bramwell, L. E. Shepherd, D. Tu, and N. Paul
Randomized Trial Comparing Cyclophosphamide, Epirubicin, and Fluorouracil With Cyclophosphamide, Methotrexate, and Fluorouracil in Premenopausal Women With Node-Positive Breast Cancer: Update of National Cancer Institute of Canada Clinical Trials Group Trial MA5
J. Clin. Oncol.,
August 1, 2005;
23(22):
5166 - 5170.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Campone, H. Roche, P. Kerbrat, J. Bonneterre, P. Romestaing, P. Fargeot, M. Namer, A. Monnier, P. Montcuquet, M.-J. Goudier, et al.
Secondary leukemia after epirubicin-based adjuvant chemotherapy in operable breast cancer patients: 16 years experience of the French Adjuvant Study Group
Ann. Onc.,
August 1, 2005;
16(8):
1343 - 1351.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
TOP
ABSTRACT
INTRODUCTION
