This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Sood, A. K. Articles by Sorosky, J. I. Search for Related Content PubMed PubMed Citation Articles by Sood, A. K. Articles by Sorosky, J. I.

Sequential Intraperitoneal Topotecan and Oral Etoposide Chemotherapy in Recurrent Platinum-Resistant Ovarian Carcinoma

Results of a Phase II Trial

¹ Department of Gynecologic Oncology, University of Texas, M. D. Anderson Cancer Center, Houston, Texas; ² H. Lee Moffitt Cancer Center & Research Institute, Tampa, Florida; and ³ Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Holden Comprehensive Cancer Center, University of Iowa Hospitals and Clinics, Iowa City, Iowa

Purpose: The purpose is to investigate the safety and efficacy of i.p. topotecan and oral etoposide as salvage treatment for patients with platinum-resistant ovarian or primary peritoneal cancer.

Experimental Design: Patients were treated with i.p. topotecan initial dose, 1 mg/m² on days 1 to 5, followed by oral etoposide 100 mg on days 6 to 9 of a 28-day cycle for six cycles. Dose reduction of topotecan was used for severe bone marrow suppression. Peritoneal (topotecan) and plasma (topotecan and etoposide) levels were assessed at multiple time points using high-pressure liquid chromatography.

Results: Twenty-two patients (mean age, 61 years) with a median of 1.5 prior treatments were enrolled. Etoposide peak plasma concentrations ranged from 1.9 to 6.9 µg/mL (mean, 3.6 µg/mL). Topotecan plasma levels rose with increasing peritoneal concentration and were detectable within 1 hour but tended to decrease rapidly to below detectable levels within 24 hours. The peak plasma concentration of topotecan was 12.82 ± 8.55 µg/mL with a plasma half-life of 6.17 ± 2.75 hours. A total of 104 cycles was administered; 14 patients (64%) completed all six planned cycles. All patients were evaluable for toxicity, and 21 patients were evaluable for response. The most common grade 4 toxicities were neutropenia and thrombocytopenia in eight and four patients (36 and 18%), respectively. There were no treatment-related deaths. The overall response rate was 38% [complete response, three (14%); partial response, five (24%)]. Seven patients had stable disease and six progressed while on treatment.

Conclusions: The combination of i.p. topotecan and oral etoposide is an active and well-tolerated regimen in platinum-resistant ovarian carcinoma. Additional studies investigating topotecan in combination with etoposide are warranted.

This article has been cited by other articles:

				M. T. Tomicic, M. Christmann, and B. Kaina Topotecan-Triggered Degradation of Topoisomerase I Is p53-Dependent and Impacts Cell Survival Cancer Res., October 1, 2005; 65(19): 8920 - 8926. [Abstract] [Full Text] [PDF]