Originally published as JCO Early Release 10.1200/JCO.2003.10.082 on June 13 2003

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Phase III Trial of Paclitaxel at Two Dose Levels, the Higher Dose Accompanied by Filgrastim at Two Dose Levels in Platinum-Pretreated Epithelial Ovarian Cancer: An Intergroup Study

George A. Omura, Mark F. Brady, Katherine Y. Look, Hervy E. Averette, James E. Delmore, Harry J. Long, Scott Wadler, Gregory Spiegel, Susan G. Arbuck

From the University of Alabama at Birmingham, Birmingham, AL; Gynecologic Oncology Group, Roswell Park Cancer Institute, and State University of New York at Buffalo, Buffalo, NY; Weill Medical College of Cornell University, New York, NY; Indiana University School of Medicine, Indianapolis, IN; Division of Gynecologic Oncology, Jackson Memorial Medical Center, University of Miami School of Medicine, Miami, FL; University of Kansas School of Medicine, Wichita, KS; Mayo Medical School, Mayo Clinic and Foundation, Rochester, MN; Division of Cancer Treatment and Diagnosis, National Cancer Institute, Bethesda, MD.

Address reprint requests to Gynecologic Oncology Group Administrative Office, 1600 John F. Kennedy Blvd, Suite 1020, Philadelphia, PA 19103.

Purpose: To determine if increasing the dose of paclitaxel increases the probability of clinical response, progression-free survival, or overall survival in women who have persistent or recurrent ovarian cancer, and whether doubling the dose of prophylactic filgrastim accompanying the higher paclitaxel dose decreases the frequency of neutropenic fever.

Patients and Methods: Consenting patients with persistent, recurrent, or progressing ovarian cancer, despite first-line platinum therapy (but no prior taxane), were randomly assigned to paclitaxel 135 mg/m², 175 mg/m², or 250 mg/m² over 24 hours every 3 weeks. Patients receiving paclitaxel 250 mg/m² were also randomly assigned to 5 or 10 µg/kg of filgrastim per day subcutaneously.

Results: Accession to the paclitaxel 135-mg/m² arm was closed early. Among the 271 patients on the other regimens with measurable disease, partial and complete response on paclitaxel 250 mg/m² (36%) was significantly higher than on 175 mg/m² (27%, P = .027). This difference was more evident among patients who never responded to prior platinum. However, progression-free and overall survival results were similar. The median durations of overall survival were 13.1 and 12.3 months for paclitaxel 175 mg/m² and 250 mg/m², respectively. Thrombocytopenia, neuropathy, and myalgia were greater with paclitaxel 250 mg/m² (P < .05). The incidence of neutropenic fever after the first cycle of paclitaxel 250 mg/m² was 19% and 18% on the 5-µg/kg and 10-µg/kg filgrastim dose, respectively (22% for paclitaxel 175 mg/m² without filgrastim).

Conclusion: Paclitaxel exhibits a dose effect with regard to response rate, but there is more toxicity and no survival benefit to justify paclitaxel 250 mg/m² plus filgrastim. Doubling the filgrastim dose from 5 to 10 µg/kg did not reduce the probability of neutropenic fever after high-dose paclitaxel.

This study was supported by National Cancer Institute grants of the Gynecologic Oncology Group Administrative Office (grant no. CA 27469), the Gynecologic Oncology Group Statistical Office (grant no. CA 37517), the Southwest Oncology Group, the Eastern Cooperative Oncology Group, and the North Central Cancer Treatment Group.

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