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Journal of Clinical Oncology, Vol 22, No 10 (May 15), 2004: pp. 1872-1877 © 2004 American Society of Clinical Oncology. DOI: 10.1200/JCO.2004.11.023
Results of a Phase II Study of Weekly Paclitaxel Plus Carboplatin in Patients With Extensive Small-Cell Lung Cancer With Eastern Cooperative Oncology Group Performance Status of 2, or Age
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ABSTRACT |
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 TOP ABSTRACT INTRODUCTIONPATIENTS AND METHODSRESULTSDISCUSSIONAppendixAuthors' Disclosures of...REFERENCES |
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70 years. PATIENTS AND METHODS: Patients were treated with PC (paclitaxel 80 mg/m2 and carboplatin area under the curve = 2) by intravenous infusion on days 1, 8, and 15 of every 4-week cycle for up to six cycles.
RESULTS: Between July 2000 and December 2001, 77 eligible patients (50.6% were male, 97.4% were white, 44.2% had PS of 2, with median age of 74 years) with ESCLC were enrolled. Among the 66 patients who were assessable for response, 25 responded to treatment (one complete response and 24 partial responses), for an objective RR of 38%. There were eight cases of stable disease (12.1%) and 33 cases of progressive disease (50%). The median survival was 7.2 months (range, < 1 to 24.4 months), and the estimated 1-year survival rate was 30%. The median TTP was 3.5 months (range, < 1 to 21.2 months), and the estimated 1-year progression-free survival rate was 8%. The median duration of response was 4.5 months (range, 1.6 to 17.5 months). One death (sepsis) was possibly related to the study drugs. Grades 3 and 4 toxicities experienced by 5% of patients included neutropenia (22.1%), fatigue (8.6%), anemia (5.2%), and nausea/vomiting (5.2%).
CONCLUSION: This regimen produced relatively few toxicities (only two of the 66 assessable patients received fewer than two cycles because of toxicity), and both the median and 1-year survival were similar to other regimens. This regimen may be a preferable treatment choice for patients with ESCLC who have a poor PS or who are aged 70 years.
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INTRODUCTION |
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TOPABSTRACTINTRODUCTIONPATIENTS AND METHODSRESULTSDISCUSSIONAppendixAuthors' Disclosures of...REFERENCES |
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Combination chemotherapy with cisplatinum (or carboplatin) plus etoposide is the present standard for treating patients with ESCLC. However, this treatment can be too toxic for many patients with ESCLC, especially those who have a compromised performance status or who are older. For example, despite a response rate (RR) of 59% and a median survival of 9 months, Larive et al7 observed a significant toxicity profile, as high incidences of grade 3 and 4 neutropenia (59%), febrile neutropenia (15%), and toxic death (9%) were seen when patients older than 70 years were treated with carboplatin plus etoposide (area under the curve [AUC] = 5 and 100 mg/m2, respectively). Moreover, Quoix et al8 used a similar dosing regimen and also found this combination to produce a substantial RR (58%), but grade 3 and 4 neutropenia (57%), febrile neutropenia (16%), and toxic death (3%) were again evident. In addition, a relatively high proportion of patients died shortly after the start of this latter study.
Carboplatin has demonstrated significant single-agent activity in ESCLC and has been the cornerstone for most combination regimens.9 Paclitaxel, if given before a platinum agent such as cisplatin or carboplatin, has been shown to intensify the cell-killing effects of DNA damage,10 and a protective or stimulatory effect on platelets has also been observed with weekly paclitaxel administration.11 Chemotherapy treatment with paclitaxel and carboplatin is usually effective for four to six cycles, dosing ranges of 135 mg/m2 to 200 mg/m2 for paclitaxel and AUC of 5 to 7 for carboplatin are typically administered, and, in most cases, treatment is given once every 3 weeks.10-21 Two recently published ESCLC studies in which this typical regimen was followed and paclitaxel, carboplatin, and an additional agent were administered (one used ifosfamide, the other etoposide) showed substantial RRs of 71% and 74%, respectively.18,21 However, both studies had notable incidences of grade 4 neutropenia (66% and 18%) and documented toxic deaths (one and three deaths). Weekly paclitaxel has been shown to be more tolerable than every-3-weeks paclitaxel,11,22-24 and minimizing toxicity is particularly important in the group of patients chosen for this trial. Because SCLC is primarily a disease of older individuals, and this population typically cannot be treated with the same doses and schedules as younger, more fit patients, alternative combinations and dosing schemes need to be evaluated.
The purpose of this trial was to evaluate a regimen that could improve survival, minimize toxicities, and allow delivery of the drugs for the intended course of treatment in a group of patients who are considered relatively frail either because of advanced age or a compromised performance status (PS). Therefore, the current study used lower doses of carboplatin and paclitaxel (80 mg/m2 and AUC = 2, respectively) within a shorter treatment window, as both were administered once a week for 3 weeks followed by 1 off-treatment week.
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PATIENTS AND METHODS |
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TOPABSTRACTINTRODUCTIONPATIENTS AND METHODSRESULTSDISCUSSIONAppendixAuthors' Disclosures of...REFERENCES |
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Patients
Eligibility criteria included patients 18 to 69 years of age with a PS of 2 by the Eastern Cooperative Oncology Group (ECOG) scale or patients 70 years of age with a PS of 0 to 2. Patients also must have had pathologically or cytologically confirmed SCLC with extensive-stage disease, defined as metastases outside the chest, pulmonary metastases, or contralateral (supraclavicular or hilar) nodes that could not be included in a single radiation port. Enrollment also required measurable or nonmeasurable but assessable disease, recovery for 3 weeks since radiotherapy to a major bone marrow–containing area or since last surgery, and threshold values for the absolute neutrophil count ( 1,500/µL), platelets ( 100,000/µL), hemoglobin ( 9 g/dL), total bilirubin (
1.5x institutional upper normal limit), and AST and ALT ( 1.5x institutional upper normal limit for each). Also, female patients were required to not be pregnant or lactating, and all patients were required to use an effective method of contraception during the study.
Exclusion criteria included prior chemotherapy for lung cancer or concurrent immunotherapy, uncontrolled parenchymal brain metastases, serious medical or psychiatric illness (including serious active infection), history of another malignancy 5 years that could have affected the diagnosis or assessment of SCLC, history of hypersensitivity to Cremophor EL (Bristol-Myers Squibb Co, Princeton, NJ), or those receiving other investigational therapy. Irradiation of an indicator lesion was not allowed, and patients could not receive any other anticancer treatment.
Treatment
Paclitaxel (Taxol; Bristol-Meyers Squibb Co) 80 mg/m2 and carboplatin (Paraplatin; Bristol-Meyers Squibb Co) AUC = 2 were administered on days 1, 8, and 15 of each 4-week cycle. No drug was administered during week 4. Patients continued therapy for up to six cycles, and all patients received premedication before the first paclitaxel infusion to prevent severe hypersensitivity reactions. The premedication regimen consisted of 20 mg of intravenous (IV) dexamethasone, 50 mg IV diphenhydramine (or its equivalent), and 300 mg cimetidine or 50 mg IV ranitidine. Subsequent premedication was used when clinically indicated. Paclitaxel and carboplatin were infused separately via an IV catheter over 1 hour and 15 to 30 minutes, respectively. Palliative and supportive care for disease-related symptoms, including but not limited to antiemetic medications, was offered to all patients in this study.
Dose Modification
No study drug dose escalations were permitted. Dose reductions were based on the system showing the greatest degree of toxicity. Toxicities were graded using the National Cancer Institute Common Toxicity Criteria (version 2.0), and a maximum of two dose reductions were allowed. If treatment was held more than 2 weeks, excluding the rest week, the patient was taken off study. Grade 1 and 2 toxicities were managed symptomatically. Grade 3 and 4 nonhematologic toxicities resulted in a 15% permanent dose decrease. Dose reductions for hematologic toxicities were also made in increments of 15%, were temporary, and were reassessed at the next visit.
Assessments
A medical history was performed at screening, at the end of each cycle, and at the end of therapy. Physical examinations (vital signs and height and body weight measurements), an ECOG PS evaluation, and clinical tumor assessments were performed at screening, each cycle, the end of therapy, and follow-up. A toxicity assessment was done at the end of each cycle and for up to 30 days after the last dose of study treatment. CBC counts with differential and platelets were conducted at screening, weekly, at the end of therapy, and during follow-up. Other assays, including serum creatinine, total bilirubin, AST, and ALT, were conducted at screening, during each cycle, and during follow-up. Radiologic tumor assessments were performed at screening, before cycles 3 and 5, and at the end of treatment.
Response Criteria
Per protocol, patients were assessable for response if they received two or more cycles, developed rapid tumor progression, or died of progressive disease (PD) before response evaluation. To confirm a partial response (PR) or complete response (CR), changes in tumor measurements were determined by repeat studies performed 4 weeks after the criteria were first met. Assessable disease was defined as disease that was assessable and could be documented on radiographs or photographs. A CR was defined as the complete disappearance of all known measurable disease as determined by two observations 4 weeks apart with no new lesions. A PR was defined as a 50% decrease in the sum of the products of the longest perpendicular diameters of all measured lesions compared with baseline and no appearance of new lesions. Stable disease (SD) was defined as no significant change in disease status and no evidence of progression as defined below. PD was defined as a 25% increase in the sum of products of all measurable lesions over the smallest sum observed (over baseline if no decrease) using the same technique performed at baseline, the appearance of a new lesion that had disappeared, a clear worsening of any assessable disease, or the appearance of any new lesion/site.
Statistical Analysis
The primary efficacy parameter of this study was the 1-year survival rate. It was estimated that 77 eligible patients would have 80% power to detect a difference between the expected 1-year survival rate for this trial of 20% and the observed 1-year survival rate of 10%, with a significance level of .05. Survival was defined as the interval between the study treatment start date and the last date of follow-up (for patients still alive) or until death. Secondary efficacy parameters included overall survival, toxicity, tumor response, duration of response, and time to progression (TTP). TTP was defined as the interval between the start date of treatment and the date of occurrence of PD. If intolerable toxicity or discontinuation of treatment secondary to toxicity occurred, the patient was considered assessable but was classified as a treatment failure. If other antitumor therapy was initiated before PD occurred, the patient was censored on the date on which the other therapy began. If a patient was lost to follow-up, the patient was censored on the date of last contact. Survival curves were estimated using the method of Kaplan and Meier.25 SAS version 8.0 (SAS Institute, Cary, NC) was used to run the analyses.
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RESULTS |
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TOPABSTRACTINTRODUCTIONPATIENTS AND METHODSRESULTSDISCUSSIONAppendixAuthors' Disclosures of...REFERENCES |
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70 years of age or had an ECOG PS of 2 were enrolled onto this phase II study. The demographics of these patients are listed in Table 1. At baseline, the median age was 74 years (range, 53 to 88 years), 50.6% were male, 97.4% were white, 36.3% had prior surgery, and 10.3% had prior radiation therapy. Baseline PS scores included 17% with a PS of 0, 39% with a PS of 1, and 44% with a PS of 2. Eleven patients were not assessable for response. Four patients died early in the study, two patients refused treatment, three patients experienced early toxicity (one patient had an allergic reaction to paclitaxel and two had thrombocytopenia), one patient transferred to another city, and one patient did not have a tumor assessment done at cycle 2. Of the 66 assessable patients, 64 completed at least two cycles of therapy (97%), and 44 completed at least four cycles of therapy (67%).
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grade 3 occurring in more than 5% of patients included neutropenia (22.1%), fatigue (8.6%), anemia (5.2%), and nausea/vomiting (5.2%). One death, caused by sepsis, was possibly related to the study drug, and one patient experienced a paclitaxel hypersensitivity reaction.
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DISCUSSION |
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TOPABSTRACTINTRODUCTIONPATIENTS AND METHODSRESULTSDISCUSSIONAppendixAuthors' Disclosures of...REFERENCES |
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2. In this trial, 58 patients were treated, but 10 patients failed to complete just two cycles of treatment. A large majority (76%) of these patients experienced grade 3 or 4 neutropenia, and three toxic deaths were related to neutropenia and sepsis. Another trial that administered this same regimen along with granulocyte colony-stimulating factor and was given to older patients (defined as age 65 years) with ESCLC concluded that this regimen was too toxic, even with the growth factor support.28 Sometimes, in an effort to minimize toxicity, efficacy is compromised. Girling looked at oral etoposide versus standard combination chemotherapy in patients with a poor PS, and the trial was stopped early because of the inferiority of oral etoposide.31 Carboplatin is often substituted for cisplatinum to reduce toxicity. In SCLC, it has been shown that efficacy is equivalent, and yet toxicity is less with carboplatin.32,33 The theory behind weekly paclitaxel-based regimens is to provide greater dose-intensity with less toxicity, as demonstrated by Akerley et al.23 Moreover, it has been shown in a number of other studies that, indeed, weekly paclitaxel is tolerable and has demonstrated substantial efficacy.11,22,24 It is also noteworthy that a review of the current literature shows that the present investigation represents the only trial of weekly paclitaxel-based chemotherapy in ESCLC.
Taking these principles into account, this trial evaluated weekly paclitaxel and carboplatin with the intent to identify a regimen that could be well tolerated and easy to deliver to completion while achieving survival results similar to or perhaps superior to historical controls. In this trial, the estimated 1-year survival rate was 30% and the median survival was 7.2 months (range, < 1 to 24.4 months). These are comparable to the results seen from trials that included patients with better PS.34-36 This trial also showed that this regimen can be delivered to a majority of patients. For example, 66 of 77 patients received at least two cycles of therapy, and 44 (67%) of 66 completed at least four cycles of therapy. Dose delay occurred in only 12% of patients, and grade 3 or 4 neutropenia occurred in only 22%. This incidence of neutropenia is significantly less compared with that seen in other trials. For example, in a large phase III trial comparing irinotecan plus cisplatinum with etoposide plus cisplatinum in patients with ESCLC with an ECOG PS of 0, 1, or 2, the incidence of grade 3 or 4 neutropenia was 65% and 92%, respectively.34 In another trial where etoposide, cisplatin, and paclitaxel were administered on a 21-day schedule to patients with ESCLC, grade 4 neutropenia was observed in 47% of patients.35 One would expect the patients in the current trial to be more likely to experience neutropenia because of their advanced age or compromised PS, but this was not the case.
In conclusion, we were able to identify a tolerable regimen in this relatively frail group of patients primarily because toxicities such as cytopenia, nausea, or fatigue were infrequent. Furthermore, RR and 1-year survival rates were comparable to those of other chemotherapeutic regimens used to treat ESCLC. The combination of paclitaxel and carboplatin administered as a weekly, low-dose treatment seems to be a promising and appropriate regimen for treating a group of patients with ESCLC who may have difficulty tolerating more established regimens.
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Appendix |
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TOPABSTRACTINTRODUCTIONPATIENTS AND METHODSRESULTSDISCUSSIONAppendixAuthors' Disclosures of...REFERENCES |
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The following medical oncologists from the US Oncology Research network institutions participated in this study: S.M. Abrams, Lauderhill, FL; L.L. Allen, Winston-Salem, NC; E. Aly, Indianapolis, IN; W.A. Andes, Wytheville, VA; R.F. Asbury, Greece, NY; R.E. Barrington, Kerrville, TX; R.J. Belt, Kansas City, MO; B.S. Berman, Altamonte Springs, FL; L. Boros, Rochester, NY; M.A. Boxer, Tucson, AZ; J.R. Caton Jr, Spokane, WA; E. Chang, Tualatin, OR; G.M. Custer, Overland Park, KS; R. DeLizio, Wichita Falls, TX; R.L. Drapkin, Clearwater, FL; J.J. Dudek, Albany, NY; G. Edelman, Irving, TX; M.E. Ellis, Williamsburg, VA; D.C. Faragher, Aurora, CO; M.R. Flores, Orlando, FL; E.R. George, Norfolk, VA; D.H. Gesme, Cedar Rapids, IA; D. Hakimian, Niles, IL; M. Hancock, Englewood, CO; E.A. Harden, Newport News, VA; J.K. Hwang, Greenfield, IN; L. Jensen, Boulder, CO; A.M. Keller, Tulsa, OK; L. Klein, Niles, IL; M. Kolodziej, Albany, NY; S. Kruger, Hampton, VA; P. Landon, Tulsa, OK; J.C. Lasker, Birmingham, AL; G.L. Lee, Eugene, OR; B.J. Marek, McAllen, TX; R.F. Marschke, Fort Collins, CO; R. McCreary, Clearwater, FL; K.J. McIntyre, Dallas, TX; B. McKenzie, Eugene, OR; B. McKenzie, Springfield, OR; D.C. Medgyesy, Fort Collins, CO; D.F. Moore, Wichita, KS; M.A. O'Rourke, Greenville, SC; R.N. Raju, Dayton, OH; A. Rastogi, Midland, TX; D.A. Richards, Tyler, TX; G. Robbins, New Port Richey, FL; S.H. Rosenhoff, Roanoke, VA; R.M. Rotche, Roanoke, VA; V. Sandor, Hampton, VA; A.M. Schneider, Lauderhill, FL; D. Schrier, Englewood, CO; J.N. Sherman, Dayton, OH; M.S. Steinberg, Norfolk, VA; S. Stone, Plano, TX; J. Thachil, Wichita Falls, TX; R.C. Tolley, Thornton, CO; H. Venkatesh, Indianapolis, IN; K.S. Weibel, Tulsa, OK; and S. Wilks, San Antonio, TX.
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Authors' Disclosures of Potential Conflicts of Interest |
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TOPABSTRACTINTRODUCTIONPATIENTS AND METHODSRESULTSDISCUSSIONAppendixAuthors' Disclosures of...REFERENCES |
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Acknowledgment |
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NOTES |
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Authors' disclosures of potential conflicts of interest are found at the end of this article.
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REFERENCES |
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TOPABSTRACTINTRODUCTIONPATIENTS AND METHODSRESULTSDISCUSSIONAppendixAuthors' Disclosures of...REFERENCES |
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2. Pass HI, Mitchell JB, Johnson DH, et al (eds): Lung Cancer: Principles and Practices (ed 2). Baltimore, MD, Lippincott Williams & Wilkins, 2000, p 613
3. Simon GR, Wagner H: Small cell lung cancer. Chest 123:259S-271S, 2003 (suppl 1)
4. American Lung Association: Trends in cigarette smoking, 6/03 update. www.lungusa.org/data/smoke/smoke_1.pdf
5. University of Pittsburgh Medical Center: Information on small cell lung cancer from The University of Pittsburgh Medical Center, 6/03 update. http://www.upmccancercenters.com/cancer/smallcell/what_prof.cfm
6. Octane Creative: Population data from Baby Boomer website, 6/03 update. http://www.octanecreative.com/boomerbaby/#factoidAnchor
7. Larive S, Bombaron P, Riou R, et al: Carboplatin-etoposide combination in small cell lung cancer patients older than 70 years: A phase II trial. Lung Cancer 35:1-7, 2002[CrossRef][Medline]
8. Quoix E, Breton JL, Daniel C, et al: Etoposide phosphate with carboplatin in the treatment of elderly patients with small-cell lung cancer: A phase II study. Ann Oncol 12:957-962, 2001
9. Smith IE, Evans BD: Carboplatin (JM8) as a single agent and in combination in the treatment of small cell lung cancer. Cancer Treat Rev 12:73-75, 1985 (suppl A)
10. Parker RJ, Dabholkar MD, Lee KB, et al: Taxol effect on cisplatin sensitivity and cisplatin cellular accumulation in human ovarian cancer cells. J Natl Cancer Inst Monogr 15:83-88, 1993
11. Akerley W: Paclitaxel in advanced non-small cell lung cancer: An alternative high-dose weekly schedule. Chest 117:152S-155S, 2000 (suppl 1)
12. Kakolyris S, Mavroudis D, Tsavaris N, et al: Paclitaxel in combination with carboplatin as salvage treatment in refractory small-cell lung cancer (SCLC): A multicenter phase II study. Ann Oncol 12:193-197, 2001
13. Groen HJ, Fokkema E, Biesma B, et al: Paclitaxel and carboplatin in the treatment of small-cell lung cancer patients resistant to cyclophosphamide, doxorubicin, and etoposide: A non-cross-resistant schedule. J Clin Oncol 17:927-932, 1999
14. Thomas P, Castelanu O, Paillotin D, et al: Phase II trial of paclitaxel and carboplatin in metastatic small-cell lung cancer: A Groupe Francais de Pneumo-Cancerologie study. J Clin Oncol 19:1320-1325, 2001
15. Gridelli C, Manzione L, Perrone F, et al: Carboplatin plus paclitaxel in extensive small cell lung cancer: A multicentre phase 2 study. Br J Cancer 84:38-41, 2001[CrossRef][Medline]
16. van Putten JW, Kerbush T, Smit EF, et al: Dose-finding and pharmacological study of ifosfamide in combination with paclitaxel and carboplatin in resistant small-cell lung cancer. Ann Oncol 12:787-792, 2001
17. Greco FA, Hainsworth JD: Paclitaxel, carboplatin, and oral etoposide in the treatment of small cell lung cancer. Semin Oncol 23:7-10, 1996
18. Hainsworth JD, Hopkins LG, Thomas M, et al: Paclitaxel, carboplatin, and extended-schedule oral etoposide for small-cell lung cancer. Oncology 12:31-35, 1998[CrossRef]
19. Socinski MA, Neubauer MA, Olivares J, et al: Phase II trial of paclitaxel, ifosfamide, and carboplatin in extensive-stage small cell lung cancer. Lung Cancer 40:91-97, 2003[CrossRef][Medline]
20. Niell HB: Extensive stage small cell lung cancer. Curr Treat Options Oncol 2:71-76, 2001[Medline]
21. Dowlati A, Crosby L, Remick SC, et al: Paclitaxel added to the cisplatin/etoposide regimen in extensive-stage small cell lung cancer: The use of complete response rate as the primary endpoint in phase II trials. Lung Cancer 32:155-162, 2001[CrossRef][Medline]
22. Michel G, Leyvraz S, Bauer J, et al: Weekly carboplatin and VM-26 for elderly patients with small cell lung cancer. Ann Oncol 5:369-370, 1994
23. Akerley W, Glantz M, Choy H, et al: Phase I trial of weekly paclitaxel in advanced lung cancer. J Clin Oncol 16:153-158, 1998
24. Chang AY, Rubins J, Asbury R, et al: Weekly paclitaxel in advanced non-small cell lung cancer. Semin Oncol 28:10-13, 2001 (suppl 14)
25. Kaplan EL, Meier P: Nonparametric estimation from incomplete observations. J Am Stat Assoc 53:457-481, 1958[CrossRef]
26. Stephens RJ, Johnson DH: Treatment and outcomes for elderly patients with small cell lung cancer. Drugs Aging 17:229-247, 2000[CrossRef][Medline]
27. Evans WK, Radwi A, Tomiak E, et al: Oral etoposide and carboplatin: Effective therapy for elderly patients with small cell lung cancer. Am J Clin Oncol 18:149-155, 1995[Medline]
28. Gridelli C, Rossi A, Barletta E, et al: Carboplatin plus vinorelbine plus G-CSF in elderly patients with extensive-stage small-cell lung cancer: A poorly tolerated regimen—Results of a multicentre phase II study. Lung Cancer 36:327-332, 2002[CrossRef][Medline]
29. Rosenberg P, Andersson H, Boman K, et al: A randomized multicenter study of single agent paclitaxel (TAXOL) given weekly versus every three weeks to patients with ovarian cancer previously treated with platinum therapy. Proc Am Soc Clin Oncol 18:368a, 1999 (abstr 1420)
30. Mackay HJ, O'Brien M, Hill S, et al: A phase II study of carboplatin and vinorelbine in patients with poor prognosis small cell lung cancer. Clin Oncol (R Coll Radiol) 15:181-185, 2003
31. Girling DJ: Comparison of oral etoposide and standard intravenous multidrug chemotherapy for small-cell lung cancer: A stopped multicentre randomised trial—Medical Research Council Lung Cancer Working Party. Lancet 348:563-566, 1996[CrossRef][Medline]
32. Satoh H, Ishikawa H, Funayama Y, et al: Management of small cell lung cancer in elderly. Anticancer Res 19:4507-4510, 1999[Medline]
33. Skarlos DV, Samantas E, Kosmidis P, et al: Randomized comparison of etoposide-cisplatin vs etoposide-carboplatin and irradiation in small-cell lung cancer: A Hellenic Co-operative Oncology Group study. Ann Oncol 5:601-607, 1994
34. Noda K, Nishiwaki Y, Kawahara M, et al: Irinotecan plus cisplatin compared with etoposide plus cisplatin for extensive small-cell lung cancer. N Engl J Med 346:85-91, 2002
35. Glisson BS, Kurie JM, Perez-Soler R, et al: Cisplatin, etoposide, and paclitaxel in the treatment of patients with extensive small-cell lung carcinoma. J Clin Oncol 17:2309-2315, 1999
36. Einhorn LH, Loehrer PJ: Hoosier Oncology Group Studies in extensive and recurrent small cell lung cancer. Semin Oncol 22:28-31, 1995
Submitted November 5, 2003; accepted February 18, 2004.
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Copyright © 2004 by the American Society of Clinical Oncology, Online ISSN: 1527-7755. Print ISSN: 0732-183X
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70 Years
