This Article Full Text Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Services Email this article to a colleague Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Save to my personal folders Download to citation manager Rights & Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Fleming, G. F. Articles by Burks, R. T. Search for Related Content PubMed PubMed Citation Articles by Fleming, G. F. Articles by Burks, R. T. Social Bookmarking                            What's this?

Phase III Trial of Doxorubicin Plus Cisplatin With or Without Paclitaxel Plus Filgrastim in Advanced Endometrial Carcinoma: A Gynecologic Oncology Group Study

From the Department of Medicine, University of Chicago, Chicago; Northwestern University Medical School and Center on Outcomes Research and Education, Evanston Northwestern Healthcare Research Institute, Evanston, IL; Gynecologic Oncology Group Statistical and Data Center, Roswell Park Cancer Institute, Buffalo, NY; Department of Obstetrics and Gynecology, Section of Gynecologic Oncology, Indiana University School of Medicine, Indianapolis, IN; Gynecologic Oncology, Riverside Methodist Hospital, Columbus, OH (affiliate of the Columbus Cancer Council); Department of Obstetrics and Gynecology, Division of Gynecologic Oncology, Wayne State University/Karmanos Cancer Institute, Detroit, MI; Division of Gynecologic Oncology, Ochsner Clinic Foundation, New Orleans, LA (affiliate of University of Mississippi); Department of Obstetrics and Gynecology, Division of Gynecologic Oncology, University of California-Irvine Medical Center, Orange, CA; Department of Obstetrics, Gynecology, Reproductive Biology, Harvard Medical School, Massachusetts General Hospital Gillette Center for Women's Cancers, Boston, MA (affiliate of Tufts-New England Medical Center, Boston); Virginia Commonwealth Health Sciences Center, Richmond, VA; and Spartanburg Pathology Associates PA, Spartanburg, SC.

Address reprint requests to Denise Mackey, Administrative Assistant, Gynecologic Oncology Group, Four Penn Center, 1600 JFK Blvd, Suite 1020, Philadelphia, PA 19103. Address other correspondence to Gini F. Fleming, MD, Section of Medical Oncology, University of Chicago, 5841 S Maryland Ave, Room I-211, MC 2115, Chicago, IL 60637; e-mail: gfleming{at}medicine.bsd.uchicago.edu

PURPOSE: To determine whether the addition of paclitaxel to doxorubicin plus cisplatin improves overall survival (OS) in women with advanced or recurrent endometrial carcinoma. Secondary comparisons included progression-free survival (PFS), response rate (RR), and toxicities.

PATIENTS AND METHODS: Eligible, consenting patients received doxorubicin 60 mg/m² and cisplatin 50 mg/m² (AP), or doxorubicin 45 mg/m² and cisplatin 50 mg/m² (day 1), followed by paclitaxel 160 mg/m² (day 2) with filgrastim support (TAP). The initial doxorubicin dose in the AP arm was reduced to 45 mg/m² in patients with prior pelvic radiotherapy and those older than 65 years. Both regimens were repeated every 3 weeks to a maximum of seven cycles. Patients completed a neurotoxicity questionnaire before each cycle.

RESULTS: Two hundred seventy-three women (10 ineligible) were registered. Objective response (57% v 34%; P < .01), PFS (median, 8.3 v 5.3 months; P < .01), and OS (median, 15.3 v 12.3 months; P = .037) were improved with TAP. Treatment was hematologically well tolerated, with only 2% of patients receiving AP, and 3% of patients receiving TAP experiencing neutropenic fever. Neurologic toxicity was worse for those receiving TAP, with 12% grade 3, and 27% grade 2 peripheral neuropathy, compared with 1% and 4%, respectively, in those receiving AP. Patient-reported neurotoxicity was significantly higher in the TAP arm following two cycles of therapy.

CONCLUSION: TAP significantly improves RR, PFS, and OS compared with AP. Evaluation of this regimen in the high-risk adjuvant setting is warranted, but close attention should be paid to the increased risk of peripheral neuropathy.

Supported by National Cancer Institute grants to the Gynecologic Oncology Group Administrative Office (CA 27469) and the Gynecologic Oncology Group Statistical Office (CA 37517).

Authors' disclosures of potential conflicts of interest are found at the end of this article.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Facebook    Reddit    Technorati    Twitter    What's this?

This article has been cited by other articles:

				J. E. Ang, R. N. Shah, M. Everard, C. Keyzor, I. Coombes, A. Jenkins, K. Thomas, R. A'Hern, R. L. Jones, P. Blake, et al. A feasibility study of sequential doublet chemotherapy comprising carboplatin-doxorubicin and carboplatin-paclitaxel for advanced endometrial adenocarcinoma and carcinosarcoma Ann. Onc., November 1, 2009; 20(11): 1787 - 1793. [Abstract] [Full Text] [PDF]

				D. S. Dizon, J. A. Blessing, D. S. McMeekin, S. K. Sharma, P. DiSilvestro, and R. D. Alvarez Phase II Trial of Ixabepilone As Second-Line Treatment in Advanced Endometrial Cancer: Gynecologic Oncology Group Trial 129-P J. Clin. Oncol., July 1, 2009; 27(19): 3104 - 3108. [Abstract] [Full Text] [PDF]

				M. M. Baekelandt, M. Castiglione, and On behalf of the ESMO Guidelines Working Group Endometrial carcinoma: ESMO Clinical Recommendations for diagnosis, treatment and follow-up Ann. Onc., May 1, 2009; 20(suppl_4): iv29 - iv31. [Full Text] [PDF]

				J. N. Bakkum-Gamez, J. Gonzalez-Bosquet, N. N. Laack, A. Mariani, and S. C. Dowdy Current Issues in the Management of Endometrial Cancer Mayo Clin. Proc., January 1, 2008; 83(1): 97 - 112. [Abstract] [Full Text] [PDF]

				G. F. Fleming Systemic Chemotherapy for Uterine Carcinoma: Metastatic and Adjuvant J. Clin. Oncol., July 10, 2007; 25(20): 2983 - 2990. [Full Text] [PDF]

				C. Humber, J. Tierney, R. Symonds, M Collingwood, J Kirwan, C Williams, and J. Green Chemotherapy for advanced, recurrent or metastatic endometrial cancer: a systematic review of Cochrane collaboration Ann. Onc., March 1, 2007; 18(3): 409 - 420. [Abstract] [Full Text] [PDF]

				K. F. Tam, T. Y. Ng, P. C. K. Tsang, C. F. Li, and Y. S. Ngan Potential Use of the Adenosine Triphosphate Cell Viability Assay in Endometrial Cancer Reproductive Sciences, October 1, 2006; 13(7): 518 - 522. [Abstract] [PDF]

				D. Dai, A. M. Holmes, T. Nguyen, S. Davies, D. P. Theele, C. Verschraegen, and K. K. Leslie A Potential Synergistic Anticancer Effect of Paclitaxel and Amifostine on Endometrial Cancer Cancer Res., October 15, 2005; 65(20): 9517 - 9524. [Abstract] [Full Text] [PDF]

				D. Dai, L. Albitar, T. Nguyen, L. L. Laidler, M. Singh, and K. K. Leslie A therapeutic model for advanced endometrial cancer: Systemic progestin in combination with local adenoviral-mediated progesterone receptor expression Mol. Cancer Ther., January 1, 2005; 4(1): 169 - 175. [Abstract] [Full Text] [PDF]

				J. T. Thigpen, M. F. Brady, H. D. Homesley, J. Malfetano, B. DuBeshter, R. A. Burger, and S. Liao Phase III Trial of Doxorubicin With or Without Cisplatin in Advanced Endometrial Carcinoma: A Gynecologic Oncology Group Study J. Clin. Oncol., October 1, 2004; 22(19): 3902 - 3908. [Abstract] [Full Text] [PDF]

				S. Aebi Endometrial cancer: a frequent orphan disease Ann. Onc., August 1, 2004; 15(8): 1149 - 1150. [Full Text] [PDF]

				G. F. Fleming, V. L. Filiaci, R. C. Bentley, T. Herzog, J. Sorosky, L. Vaccarello, and H. Gallion Phase III randomized trial of doxorubicin + cisplatin versus doxorubicin + 24-h paclitaxel + filgrastim in endometrial carcinoma: a Gynecologic Oncology Group study Ann. Onc., August 1, 2004; 15(8): 1173 - 1178. [Abstract] [Full Text] [PDF]