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 Rose, P. G. Articles by McGuire, W. P. Search for Related Content PubMed PubMed Citation Articles by Rose, P. G. Articles by McGuire, W. P. Social Bookmarking                            What's this?

Phase I Study of Paclitaxel, Carboplatin, and Increasing Days of Prolonged Oral Etoposide in Ovarian, Peritoneal, and Tubal Carcinoma: A Gynecologic Oncology Group Study

From the Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Case Western Reserve University, University Hospitals of Cleveland, Cleveland; Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Ohio State University, James Cancer Hospital and Solove Research Institute, Columbus, OH; Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, University of Chicago, Chicago, IL; Division of Gynecologic Oncology, University of Washington School of Medicine, Seattle, WA; Division of Gynecology and Obstetrics, Emory University School of Medicine, Atlanta, GA; University of Mississippi School of Medicine, Jackson, MS; and Chemotherapy Services, Gynecologic Cancer Center, Mercy Medical Center, Baltimore, MD.

Address reprint requests to Gynecologic Oncology Group Administrative Office, Suite 1945, 1234 Market St, Philadelphia, PA 19107.

PURPOSE: Given the activity of prolonged oral etoposide in platinum and paclitaxel-resistant ovarian carcinoma, a phase I trial was conducted that combined increasing days of oral etoposide therapy with paclitaxel and carboplatin in chemotherapy-naive patients with ovarian peritoneal and tubal carcinoma to establish a maximum-tolerated dose (MTD) of this combination.

PATIENTS AND METHODS: Paclitaxel at 175 mg/m² given over 3 hours and carboplatin at an area under the curve of 5 were administered on day 1 followed by oral etoposide 50 mg/m²/d beginning on day 2. The number of days of etoposide therapy was escalated on the basis of toxicity. Toxicity end points included neutropenic sepsis, grade 4 thrombocytopenia, or grade 3 neutropenia or thrombocytopenia during etoposide administration. Cycles were repeated every 21 days for a maximum of six courses. Due to hematologic toxicity, the duration of the paclitaxel infusion was decreased to 1 hour for a second stage of accrual.

RESULTS: Of 52 patients studied, 29 were in the first stage of accrual. Dose-limiting toxicity occurred with 8 days of oral etoposide, making the MTD six days of therapy. Twenty-three patients were entered into the second stage of accrual. Dose-limiting toxicity occurred at 12 days of oral etoposide, making the MTD 10 days of therapy. Three patients developed acute myeloid leukemia 16, 27, and 35 months after receiving a cumulative dose of 200 mg/m², 1,200 mg/m², and 2,400 mg/m², respectively.

CONCLUSION: One-hour paclitaxel, carboplatin, and oral etoposide at 50 mg/m²/d for 10 days is tolerable without supportive therapy. The leukemogenic potential is cause for concern and precludes its use in chemotherapy-naive ovarian carcinoma.

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

This article has been cited by other articles:

				M. A. Bookman Developmental Chemotherapy and Management of Recurrent Ovarian Cancer J. Clin. Oncol., May 15, 2003; 21(90100): 149s - 167. [Abstract] [Full Text] [PDF]