Journal of Clinical Oncology, Vol 10, 727-734, Copyright © 1992 by American Society of Clinical Oncology
Dose-intensive induction therapy with cyclophosphamide, cisplatin, and consolidative abdominal radiation in advanced-stage epithelial ovarian cancer
ML Rothenberg, RF Ozols, E Glatstein, SM Steinberg, E Reed and RC Young
Medicine Branch, National Cancer Institute, Bethesda, MD.
PURPOSE: The primary goal of this trial was to evaluate the clinical
activity of a high-dose cisplatin-based induction regimen for women with
advanced-stage ovarian cancer. A secondary goal was to assess the use of
whole-abdominal radiation as consolidative therapy in the subset of women
left with less than 5 mm residual disease after completion of chemotherapy.
PATIENTS AND METHODS: Fifty consecutive patients with newly diagnosed,
advanced-stage ovarian cancer received cisplatin 40 mg/m2/d and
cyclophosphamide 200 mg/m2/d intravenously (IV) for 5 days, every 4 to 6
weeks. After three to four cycles of chemotherapy, patients who still had
residual disease less than 5 mm in greatest diameter at second-look surgery
were given whole-abdominal radiotherapy. RESULTS: The overall response rate
in 49 patients assessable for response was 61.3% (24.5% pathologic complete
responses [pCRs], 32.7% pathologic partial responses [pPRs], and 4.1%
clinical partial responses [cPRs]). Median survival for all patients was
23.4 months, and actuarial 4-year survival was 33.7% (95% confidence
interval [CI], 21.8% to 48.1%). Multivariate analysis showed stage III and
serous histology as independent favorable prognostic factors for survival.
Median survival for stage III patients was 36.5 months, with an actuarial
4-year survival of 41.6% (95% CI, 25.5% to 59.6%). Median survival for
stage IV patients was 12.0 months, with actuarial 4-year survival of 22.9%
(95% CI, 9.5% to 45.5%). The major acute toxicities encountered were
myelosuppression and peripheral neuropathy. Patients who received
consolidative radiotherapy were at increased risk of developing late-onset
enteropathy. CONCLUSIONS: This regimen is active against advanced-stage
ovarian cancer, but the associated toxicity is severe. Consolidative
whole-abdominal radiation did not appear to prolong survival in the subset
of women left with less than 5 mm residual disease after chemotherapy.
