A phase I trial of gemcitabine and topotecan in previously treated ovarian or peritoneal cancer: a Gynecologic Oncology Group study.

Abstract

OBJECTIVE:

To determine the maximum tolerated dose (MTD) of the combination of gemcitabine and topotecan in women with previously treated epithelial ovarian, peritoneal, or fallopian tube cancer.

METHODS:

Patients with recurrent or persistent cancer after treatment with a platinum and paclitaxel-containing regimen were eligible for this study. Initial treatment was gemcitabine at a dose of 800 mg/m(2) on days 1, 8, and 15 and topotecan at a dose of 0.5 mg/m(2) on days 2-5, with cycles repeated every 28 days. Dose escalations were planned first for topotecan (Cohort I, Dose Levels 1-5) then for gemcitabine (Cohort II, Dose Levels 6-9) until the MTD was reached.

RESULTS:

Ten patients received a total of 29 cycles. When none of the first four patients could complete therapy as prescribed due to toxicity, doses for each drug were reduced by 1 day. The next six patients were treated at the modified schedule of gemcitabine days 1 and 8 and topotecan days 2-4 (Dose Level -1). Despite this modification, dose-limiting toxicities including neutropenia, thrombocytopenia, and stomatitis occurred at Dose Level -1, and the study was closed early.

CONCLUSIONS:

At both the initial dose schedule and an attenuated schedule, the combination of gemcitabine and topotecan produced dose-limiting toxicities in women with previously treated epithelial ovarian or peritoneal cancer.

• Authors: M Dwight Chen, Gini F Fleming, Suann Mitchell, Ira Horowitz
• Journal: Gynecologic oncology (Gynecol Oncol) Vol. 100 Issue 1 Pg. 111-5 (Jan 2006) ISSN: 0090-8258 [Print] United States
• PMID: 16150481 (Publication Type: Clinical Trial, Phase I, Journal Article, Multicenter Study, Research Support, N.I.H., Extramural)

Chemical References

• Deoxycytidine
• Topotecan
• Gemcitabine

Topics

• Aged
• Antineoplastic Combined Chemotherapy Protocols (adverse effects, therapeutic use)
• Deoxycytidine (administration & dosage, adverse effects, analogs & derivatives)
• Dose-Response Relationship, Drug
• Fallopian Tube Neoplasms (drug therapy)
• Female
• Humans
• Middle Aged
• Neoplasm Recurrence, Local (drug therapy)
• Ovarian Neoplasms (drug therapy)
• Peritoneal Neoplasms (drug therapy)
• Topotecan (adverse effects, therapeutic use)
• Gemcitabine