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Journal of Clinical Oncology, Vol 22, No 19 (October 1), 2004: pp. 3902-3908 © 2004 American Society of Clinical Oncology. DOI: 10.1200/JCO.2004.02.088 Phase III Trial of Doxorubicin With or Without Cisplatin in Advanced Endometrial Carcinoma: A Gynecologic Oncology Group StudyFrom the Division of Oncology, Department of Medicine, University of Mississippi School of Medicine, Jackson, MS; Gynecologic Oncology Group Statistical and Data Center, Roswell Park Cancer Institute, Buffalo; Obstetrics and Gynecology, Division of Gynecologic Oncology, Albany Medical Center Hospital, Albany; Department of Obstetrics and Gynecology, University of Rochester School of Medicine, Rochester, NY; Wake Forest University School of Medicine, Winston-Salem, NC; Department of Obstetrics and Gynecology, Division of Gynecologic Oncology, University of California at Irvine Medical Center; and Department of Pathology, University of California at Irvine, Orange, CA Address reprint requests to Denise Mackey, Gynecologic Oncology Group Administrative Office, Four Penn Center, 1600 John F. Kennedy Blvd, Suite 1020, Philadelphia, PA 19103
PURPOSE: Doxorubicin and cisplatin have activity in endometrial carcinoma and at initiation of this study ranked as the most active agents. This trial of stage III, IV, or recurrent disease evaluated whether combining these agents increases response rate (RR) and prolongs progression-free survival (PFS) and overall survival (OS) over doxorubicin alone. PATIENTS AND METHODS: Of 299 patients registered, 281 (94%) were eligible. Regimens were doxorubicin 60 mg/m2 intravenously or doxorubicin 60 mg/m2 plus cisplatin 50 mg/m2 every 3 weeks until disease progression, unacceptable toxicity, or a total of 500 mg/m2 doxorubicin. RESULTS: There were 12 (8%) complete (CR) and 26 (17%) partial responses (PR) among 150 patients receiving doxorubicin versus 25 (19%) CRs and 30 (23%) PRs among patients receiving the combination. The overall response rate was higher among patients receiving the combination (42%) compared with patients receiving doxorubicin (25%; P = .004). Median PFS was 5.7 and 3.8 months, respectively, for the combination and single agent. The PFS hazard ratio was 0.736 (95% CI, 0.577 to 0.939; P = .014). Median OS was 9.0 and 9.2 months, respectively, for the combination and single agent. Overall death rates were similar in the two groups (hazard ratio, 0.928; 95% CI, 0.727 to 1.185). Nausea, vomiting, and hematologic toxicities were common. The combination produced more grade 3 to 4 leukopenia (62% v 40%), thrombocytopenia (14% v 2%), anemia (22% v 4%), and nausea/vomiting (13% v 3%). CONCLUSION: Adding cisplatin to doxorubicin in advanced endometrial carcinoma improves RR and PFS with a negligible impact on OS and produces increased toxicity. These results have served as a building block for subsequent phase III trials in patients with disseminated and high-risk limited endometrial carcinoma.
In the United States, endometrial carcinoma is the most common invasive malignancy of the female genital tract.1 It has a well-earned reputation for a very favorable prognosis resulting from the fact that, at presentation, 75% of cases are stage I and an additional 13% are stage II. Most patients with stage I or II disease achieve cure with surgical resection. Although there may have been a recent shift away from this treatment approach, historically (even for those patients with more advanced or recurrent disease) progestins were routinely used as systemic therapy because endometrial carcinoma was regarded as a hormonally responsive disease. These facts slowed the development of effective cytotoxic chemotherapy for the disease. Despite this, by the early 1990s, the Gynecologic Oncology Group (GOG) had identified at least two active agents, doxorubicin and cisplatin, resulting from a series of concerted phase II trials initiated in 1976 (the activity of taxanes was not identified until later). In the absence of any evidence to support the routine use of combination chemotherapy in endometrial carcinoma, the GOG initiated a phase III randomized trial comparing doxorubicin, the single agent with the highest reported response rate,2 with a combination of that agent plus cisplatin, another active agent.3 The results of this trial led to a series of studies in both disseminated and limited high-risk endometrial carcinoma to establish a firm role for chemotherapy in both settings. Further, it formed the basis for the regimen currently used as the chemotherapy arm in studies of the treatment of optimally debulked stage III and IV disease.4,5 The following report presents the detailed final results of this critical trial, GOG Protocol 107, for the first time.
Eligibility Criteria Patients were to have histologically documented stage III, IV, or recurrent endometrial carcinoma after prior surgery and/or radiotherapy. Disease was to be measurable and patients were to have had no prior cytotoxic chemotherapy (although they may have been treated with hormonal or one prior biologic therapy). Pretreatment laboratory assessment included a leukocyte count greater than 3000/µL, a platelet count greater than 100,000/µL, creatinine less than 2.0 mg/dL, and AST, alkaline phosphatase, and bilirubin less than twice normal. In addition, patients must have exhibited a GOG performance status of 0 to 2 (equivalent to a Karnofsky score of 50% or better), with no contraindication to the use of cisplatin, no history of congestive heart failure or abnormal cardiac compensation, and no history of a previous invasive malignancy other than skin cancer (excluding melanoma). Multiple-gated acquisition scans were required to document a normal ejection fraction before study entry. All patients provided signed informed consents consistent with Federal, State, and local regulations before entering the study. From each patient, hematoxylin and eosin stained slides representative of the primary tumor and metastatic tumor were to be submitted and reviewed centrally by two members of the GOG Pathology Committee. Disagreements regarding eligibility were arbitrated by a third pathologist if necessary. These reviews were blinded to the treatment outcomes.
Treatment
End Points PFS was defined as the time from entry onto study to evidence of first disease progression, death, or date of last contact, if the patient was alive and progression-free. Overall survival was assessed as the date the patient was registered onto the study to the date of death, regardless of cause, or the date of last contact, if the patient was alive. Toxicity was graded according to the GOG Common Toxicity Criteria.6
Statistical Considerations On the basis of an expected response rate to doxorubicin of 22% (that was seen in GOG Protocol 48), the study sought to identify an increase of 15% in response rate to 37%. The planned sample size of 140 eligible patients enrolled onto each treatment group permits an 84% chance of detecting this size treatment effect with a one-sided test of significance at the .05 level. Provided that at least 75% of the patients experienced progression or death, this sample size also permits a 90% chance of detecting a treatment that effectively increases median duration of PFS or overall survival by 50% when the type I error is set to .05 for a one-tail test. The statistical test of independence between randomly assigned treatment and time-to-event outcomes was assessed with a Cox’s proportional hazards model adjusted for initial performance status.7 In this report, all significance tests are two-tailed. The primary treatment comparisons of benefit include all eligible patients, regardless of the amount of study treatment received. Both eligible and ineligible patients are included in the analyses and compared by treatment assignment when an intent-to-treat analysis is specifically indicated in this article. The summaries of toxicity include all patients who received any study treatment; those who did not receive study treatment are not included in these summaries.
Patient Characteristics GOG member institutions entered 299 patients with advanced or recurrent endometrial carcinoma onto this study. Of these, 18 were ineligible on detailed quality control review because of the following: synchronous ovarian primary tumor (three patients), primary other than endometrial carcinoma (nine patients), uncertain origin of primary tumor (three patients), ineligible cell type (two patients), and inadequate pathology materials for review (one patient). Of the 281 eligible patients, 278 received the designated study agent(s) and were evaluated for toxicity. Patient characteristics of the 281 eligible patients are listed in Table 1. The median age is 66.9 years and 64.4 years for patients on the single-agent and combination regimens, respectively. Most patients (65%) had prior radiotherapy and 32% had prior hormonal therapy.
The median and interquartile range of the doxorubicin dose delivered during the first course of treatment was 45 mg/m2 (range, 44.7 to 55.3 mg/m2) and 45 mg/m2 (range, 44.7 to 59.2 mg/m2) for patients randomly assigned to the single-agent and combination regimen, respectively. These doses reflect the fact that most patients were started at the lower doxorubicin dose per protocol because of age older than 65 years or having had prior radiation therapy. There were three eligible patients who did not receive any of their assigned study treatment. The number of courses of study treatment delivered is summarized in Table 2 by randomly assigned treatment group.
Response Clinical response is summarized in Table 3 for 281 eligible patients. Twenty patients did not have repeat tumor measurements for response assessment. In four patients receiving doxorubicin and in six patients receiving doxorubicin plus cisplatin, death or significant physical deterioration precluded disease reassessment. In the remaining 10 patients (five in each regimen), excessive toxicity or patient refusal precluded disease reassessment. All of these cases are included in Table 3 as having no clinical response. There were 37 CRs and 56 PRs, for an overall response rate of 33%. Among those patients who were randomly assigned to doxorubicin plus cisplatin, there were 25 CRs (19%) and 30 PRs (23%), whereas among those randomly assigned to single-agent doxorubicin, there were 12 CRs (8%) and 26 PRs (17%). The superior response rate (CR plus PR) observed in the combination regimen was statistically significant (P = .004). The percentage of CRs was also higher for the combination regimen (P = .008).
PFS and Overall Survival PFS is depicted graphically in Figure 1. Patients who received the combination regimen demonstrated longer PFS on average when compared with those who received single-agent doxorubicin, with a median of 5.7 versus 3.8 months. After adjusting for the initial performance status, the estimated hazard rate of first progression or death on the combination regimen is 0.736 (95% CI, 0.577 to 0.939; P = .014) times the rate on the single-agent regimen. The estimated hazard ratio is 0.748 when all eligible and ineligible (n = 299) patients are included for an intent-to-treat analysis.
Overall survival is shown in Fig 2. Overall survival for each regimen was similar, with a median of 9.0 months for the combination arm versus 9.2 months for the single-agent arm. After adjusting for the initial performance status, the death rate on the combination regimen was 0.928 times (95% CI, 0.727 to 1.185) the death rate observed on the single-agent regimen. The estimated hazard ratio for the intent-to-treat analysis is 0.953. Neither of these analyses indicates a significant difference between treatment groups in overall survival.
Adverse Effects As shown in Table 4, hematologic adverse effects manifesting as leukopenia, thrombocytopenia, and anemia were common. Leukopenia was more common in the combination therapy, with 84% versus 72% (all grades) and 62% versus 40% (grade 3 to 4). Although less problematic than leukopenia, thrombocytopenia was also observed with more frequency and severity in the combination arm: 50% versus 17% (all grades) and 14% versus 2% (grade 3 to 4). A similar effect was seen with anemia: 69% versus 42% (all grades) and 22% versus 4% (grade 3 to 4). Nausea and vomiting were also often reported, with greater frequency and severity in the combination arm: 50% versus 30% (all grades) and 13% versus 3% (grade 3 to 4). Renal toxicity was reported more frequently among those on the combination arm: 10% versus 0% (all grades).
In 1976, only three cytotoxic agents had exhibited potential activity in endometrial carcinoma on the basis of data collected from broad phase II trials: fluorouracil, cyclophosphamide, and doxorubicin.1 At that time, the GOG and others initiated efforts to evaluate single agents in phase II trials, eventually completing studies of 29 drugs over the ensuing 25 years.2,3,8-23 Among them, the anthracyclines doxorubicin and epirubicin, the platinum analogs cisplatin and carboplatin, and paclitaxel, vincristine, and fluorouracil, have shown phase II evidence of significant activity, with response rates  15%. The agents with the highest response rates include the anthracyclines, the platinum compounds, and paclitaxel, as illustrated in Table 5. 2,3,8-23 By 1988, only doxorubicin and the platinum compounds had shown evidence of significant activity, and most efforts to evaluate combination regimens in the treatment of endometrial carcinoma consisted of small, uncontrolled series without opportunity to assess the relative merits of combination and single-agent therapy.24
During that 25-year period, the GOG also conducted six randomized trials (five in addition to the current report) seeking to identify effective combinations of chemotherapy for the treatment of this disease (Table 6).25-29 The first, based on two promising pilot studies, randomly assigned patients to megestrol acetate plus either cyclophosphamide, doxorubicin, and fluorouracil or melphalan plus fluorouracil.25 Although the pilot results were encouraging, the phase III comparison (Table 6) revealed insignificant differences in response rates, PFS, and overall survival, and results were similar to those reported with single agents.25 The second GOG phase III trial randomly assigned patients to doxorubicin with or without cyclophosphamide (Table 6).26 Among 202 patients with measurable disease, doxorubicin yielded a response rate of 22% and a median survival of 6.8 months versus 32% and 7.6 months, respectively, for the combination; thus the combination offered no advantage over single-agent therapy.26
The subject of the current report was the third among the six GOG randomized trials and the first to demonstrate some advantage to combination chemotherapy. As presented in Results, doxorubicin plus cisplatin increases the proportion of responding patients and prolongs PFS (Table 3, Figs 1 and 2), although these improvements exact more toxicity in the form of myelosuppression and gastrointestinal effects (Table 4). Since completing this study, the GOG has conducted three additional phase III randomized trials. The first compared standard-timed doxorubicin plus cisplatin as reported herein to a circadian-timed regimen of the same two drugs, administering doxorubicin at 6 AM and cisplatin at 6 PM on day 1 of each 3 weeks (Table 6).27 The second compared doxorubicin plus cisplatin as reported in this article with doxorubicin 50 mg/m2 plus paclitaxel 150 mg/m2/24 hours plus granulocyte colony-stimulating factor, finding no significant differences in response rates, PFS, or overall survival (Table 6). Toxicity favored the doxorubicin plus cisplatin combination.28 In the third trial, patients were randomly assigned to either doxorubicin plus cisplatin or an aggressive combination of doxorubicin plus cisplatin plus paclitaxel (Table 6).29 It is important to note that the subject of this report, doxorubicin plus cisplatin as defined by GOG Protocol 107, was selected as the control arm in the three most recent GOG randomized trials. Several additional points are noteworthy. First, some contend that carboplatin should be substituted for cisplatin, because carboplatin seems to have similar activity as a single agent. This is not unreasonable. However, given that the three-drug combination in the most recently completed GOG study (Protocol 177) demonstrated improvement in response and survival compared with the doublet,4 the substitution of carboplatin might create problems related to excessive myelosuppression. Such a three-drug combination should be piloted first. In lieu of studying what might be a very toxic three-drug carboplatin-based regimen, the GOG is currently randomly assigning patients with advanced (stage IVB) or recurrent disease to either the three-drug cisplatin-based regimen from Protocol 177 or to paclitaxel plus carboplatin to determine whether it is possible to drop doxorubicin from the regimen and substitute carboplatin for cisplatin without loss of efficacy and with a marked improvement in the toxicity profile (GOG Protocol 209). Second, improvements in response reported to date are not large, whereas there is notable increase in the observed toxicity. Some have argued that the trade-off between improved efficacy and increased toxicity is insufficient to justify the use of the more toxic combination. This is obviously an issue to be discussed with patients before the initiation of therapy. In conclusion, this study demonstrates significant improvement in response rate and PFS when cisplatin is added to doxorubicin in the treatment of patients with advanced or recurrent endometrial carcinoma. An improvement in overall survival does not accompany the improvements in PFS and response rate, and the combination regimen does produce increased toxicity. The judgment of the investigators is that the magnitude of the increase in both the overall and complete response rates, as well as in PFS, is sufficient justification for the use of the combination. The importance of these observations is striking when viewed in terms of subsequent phase III studies of combination chemotherapy (as well as a phase III trial in patients with high-risk limited stage III to IVA disease) that used this doublet regimen as a building block. An even more recent example of its continuing relevance was reported at the Plenary Session of the 2003 Annual Meeting of the American Society of Clinical Oncology, which provided evidence from GOG Protocol 122 that this doublet administered after surgical bulk reduction in stage III to IVA disease produces superior PFS and overall survival when compared with surgery followed by abdominopelvic radiation.5 This lends further support to the current article, in which the basis for establishing a firm role for combination chemotherapy in the management of endometrial carcinoma is first presented.
The following member institutions participated in this study: University of Alabama - Birmingham, AL; Oregon Health Sciences - Portland, OR; Duke University Medical Center - Durham, NC; Abington Memorial - Abington, PA; University of Rochester - Rochester, NY; Walter Reed Army Medical Center - Washington, DC; Wayne State University - Detroit, MI; University of Minnesota Med School - Minneapolis, MN; University of Southern California at Los Angeles - Los Angeles, CA; University of Mississippi Medical Center - Jackson, MS; Colorado Gynecologic Oncology Group Professional Corp - Denver, CO; University of California at Los Angeles - Los Angeles, CA; University of Miami School of Medicine - Miami, FL; Milton S. Hershey Medical Center - Hershey, PA; Georgetown University Hospital - Washington, DC; University of Cincinnati - Cincinnati, OH; University of North Carolina - Chapel Hill, NC; University of Iowa Hospitals and Clinics - Iowa City, IA; University of Texas Southwestern Medical Center at Dallas - Dallas, TX; Indiana University Medical Center - Indianapolis, IN; Wake Forest University - Winston-Salem, NC; Albany Medical College - Albany, NY; University of California Medical Center at Irvine - Orange, CA; Tufts-New England Medical Center - Boston, MA; Rush-Presbyterian-St Luke’s - Chicago, IL; SUNY Downstate - Brooklyn, NY; University of Kentucky - Lexington, KY; Eastern Virginia Medical School - Norfolk, VA; The Cleveland Clinic - Cleveland, OH; Johns Hopkins - Baltimore, MD; SUNY at Stony Brook - Stony Brook, NY; Eastern Pennsylvania Gynecology/Oncology Center PC - Philadelphia, PA; Washington University School of Medicine - St Louis, MO; Memorial Sloan-Kettering Cancer Center - New York, NY; Cooper Hospital - Camden, NJ; Columbus Cancer Council - Columbus, OH; University of Massachusetts Medical Center - Worcester, MA; Fox Chase Cancer Center - Philadelphia, PA; Medical University of South Carolina - Charleston, SC; Women’s Cancer Center - Los Gatos, CA; University of Oklahoma - Oklahoma City, OK; University of Virginia - Charlottesville, VA.
The following authors or their immediate family members have indicated a financial interest. No conflict exists for drugs or devices used in a study if they are not being evaluated as part of the investigation. Acted as a consultant within the last 2 years: J. Tate Thigpen, Bristol-Myers Squibb Co. Received more than $2,000 per year from a company for either of the last 2 years: J. Tate Thigpen, Bristol-Myers Squibb Co.
Supported by National Cancer Institute grants to the Gynecologic Oncology Group Administrative Office (grant No. CA 27469) and the Gynecologic Oncology Group Statistical Office (grant No. CA 37517). Authors’ disclosures of potential conflicts of interest are found at the end of this article.
1. DeVita VT Jr, Wasserman T, Young RC, et al: Perspectives and research in gynecologic oncology. Cancer 38:509-525, 1976[CrossRef][Medline] 2. Thigpen JT, Buchsbaum H, Mangan C, et al: Phase II trial of adriamycin in the treatment of advanced or recurrent endometrial carcinoma: A Gynecologic Oncology Group study. Cancer Treat Rep 63:21-27, 1979[Medline] 3. Thigpen JT, Blessing JA, Homesley H, et al: Phase II trial of cisplatin as first-line chemotherapy in patients with advanced or recurrent endometrial carcinoma: A Gynecologic Oncology Group study. Gynecol Oncol 33:68-70, 1989[CrossRef][Medline]
4. Fleming GF, Brunetto VL, Cella D, et al: Phase III trial of doxorubicin plus cisplatin with or without paclitaxel plus filgrastim in advanced endometrial carcinoma: A Gynecologic Oncology Group study. J Clin Oncol 22:2159-2166, 2004 5. Randall ME, Brunetto G, Muss H, et al: Whole abdominal radiotherapy versus combination doxorubicin-cisplatin chemotherapy in advanced endometrial carcinoma: A randomized phase III trial of the Gynecologic Oncology Group. Proc Am Soc Clin Oncol 22:2, 2003 (abstr 3) 6. Blessing JA: Design, analysis and interpretation of chemotherapy trials in gynecologic cancer, in Deppe G (ed): Chemotherapy of Gynecologic Cancer (ed 2). New York, NY, Alan R. Liss, 1990, pp 63-97 7. Cox DR: Regression models and life tables (with discussion). J R Stat Soc B 34:187-220, 1972 8. Thigpen JT, Blessing JA, Homesley H, et al: Phase II trial of piperazinedione in the treatment of advanced or recurrent endometrial carcinoma. Am J Clin Oncol 9:21-23, 1986[Medline] 9. Thigpen JT, Blessing JA, Ball H, et al: Hexamethylmelamine as first-line chemotherapy in the treatment of advanced or recurrent carcinoma of the endometrium: A phase II trial of the Gynecologic Oncology Group. Gynecol Oncol 31:435-438, 1988[CrossRef][Medline] 10. Muss H, Blessing J, Hatch K, et al: Methotrexate in advanced endometrial carcinoma: A phase II trial of the Gynecologic Oncology Group. Am J Clin Oncol 13:61-63, 1990[Medline] 11. Thigpen JT, Blessing JA, Lagasse L, et al: Phase II trial of cisplatin as second-line chemotherapy in patients with advanced or recurrent endometrial carcinoma. Am J Clin Oncol 7:253-256, 1984[Medline] 12. Asbury R, Blessing JA, McGuire W, et al: Aminothiadiazole in patients with advanced carcinoma of the endometrium. Am J Clin Oncol 13:39-41, 1990[Medline] 13. Muss H, Bundy B, Adcock L: Teniposide in patients with advanced endometrial carcinoma (a phase II trial of the Gynecologic Oncology Group). Am J Clin Oncol 14:36-37, 1991[Medline] 14. Slayton R, Blessing J, DiSaia P, et al: A phase II clinical trial of diaziquone in the treatment of patients with recurrent endometrial carcinoma. Am J Clin Oncol 11:612-613, 1988[Medline] 15. Muss H, Bundy B, DiSaia P, et al: Mitoxantrone for carcinoma of the endometrium: A phase II trial of the Gynecologic Oncology Group. Cancer Treat Rep 71:217-218, 1987[Medline] 16. Homesley H, Blessing J, Conroy J, et al: ICRF-159 (Razoxzane) in patients with advanced adenocarcinoma of the endometrium. Am J Clin Oncol 9:15-17, 1986[Medline] 17. Slayton R, Blessing J, Delgado G: Phase II trial of etoposide in the management of advanced or recurrent endometrial carcinoma: A Gynecologic Oncology Group study. Cancer Treat Rep 66:1669-1671, 1982[Medline] 18. Stehman F, Blessing J, Delgado G, et al: Phase II evaluation of dianhydrogalactitol in the treatment of advanced endometrial adenocarcinoma: A Gynecologic Oncology Group study. Cancer Treat Rep 67:737-738, 1983[Medline] 19. Thigpen T: Systemic therapy with single agents for advanced or recurrent endometrial carcinoma, in Alberts D, Surwit E (eds): Endometrial Carcinoma. Boston, MA, Martinus Nijhoff, 1989 20. Barton C, Buxton EJ, Blackledge G, et al: A phase II study of ifosfamide in endometrial cancer. Cancer Chemother Pharmacol 26:S4-S6, 1990 (suppl) 21. Muss H: Chemotherapy of metastatic endometrial cancer. Semin Oncol 21:107-113, 1994 22. Hilgers R, Legha S, Johnston G, et al: M-AMSA and adenocarcinoma of the endometrium. Invest New Drugs 2:335-338, 1984[Medline] 23. Thigpen T, Vance R, Khansur T: The platinum compounds and paclitaxel in the management of carcinomas of the endometrium and uterine cervix. Semin Oncol 22:67-75, 1995[Medline] 24. Moore TD, Phillips PH, Nerenstone SR, et al: Systemic treatment of advanced and recurrent endometrial carcinoma: Current status and future directions. J Clin Oncol 9:1071-1088, 1991[Abstract] 25. Cohen C, Bruckner H, Deppe G, et al: Multidrug treatment of advanced and recurrent endometrial carcinoma: A Gynecologic Oncology Group study. Obstet Gynecol 63:719-726, 1984[Medline] 26. Thigpen JT, Blessing JA, DiSaia PJ, et al: A randomized comparison of doxorubicin alone versus doxorubicin plus cyclophosphamide in the management of advanced or recurrent endometrial carcinoma. J Clin Oncol 12:1408-1414, 1994[Abstract]
27. Gallion HH, Brunetto VL, Cibull M, et al: Randomized phase III trial of standard timed doxorubicin plus cisplatin versus circadian timed doxorubicin plus cisplatin in stage III and IV or recurrent endometrial carcinoma: A Gynecologic Oncology Group study. J Clin Oncol 21:3808-3813, 2003 28. Fleming G, Brunetto V, Bentley R, et al: Randomized trial of doxorubicin plus cisplatin versus doxorubicin plus paclitaxel plus granulocyte colony-stimulating factor in patients with advanced or recurrent endometrial cancer: A report on Gynecologic Oncology Group Protocol 163. Proc Am Soc Clin Oncol 19:379a, 2000 (abstr 1498) 29. Fleming GF, Brunetto VL, Mundt AJ, et al: Randomized trial of doxorubicin (DOX) plus cisplatin (CIS) versus DOX plus CIS plus paclitaxel (TAX) in patients with advanced or recurrent endometrial carcinoma: A Gynecologic Oncology Group Study. Proc Am Soc Clin Oncol 21:202a, 2002 (abstr 807) Submitted February 20, 2003; accepted July 19, 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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ABSTRACT
INTRODUCTION
