David S. Alberts, P.Y. Liu, Edward V. Hannigan, Robert O'Toole, Stephen D. Williams, James A. Young, Ernest W. Franklin, Daniel L. Clarke-Pearson, Vinay K. Malviya, Brent DuBeshter, Mark D. Adelson, William J. Hoskins
- Background. Intravenous platinum-based chemotherapy is the standard primary therapy for advanced ovarian cancer. We conducted a phase 3 trial to compare the effects of intraperitoneal and intravenous cisplatin on the survival of women with previously untreated, stage III, epithelial ovarian cancer.
Methods. The patients underwent an initial exploratory laparotomy and resection of all tumor masses larger than 2 cm. Within four weeks after surgery, six courses of intravenous cyclophosphamide (600 mg per square meter of body-surface area per course) plus either intraperitoneal cisplatin (100 mg per square meter) or intravenous cisplatin (100 mg per square meter) were administered at three-week intervals.
Results. Of 654 randomized patients, 546 were eligible for the study. The estimated median survival was significantly longer in the group receiving intraperitoneal cisplatin (49 months; 95 percent confidence interval, 42 to 56) than in the group receiving intravenous cisplatin (41 months; 95 percent confidence interval, 34 to 47). The risk of death was lower in the intraperitoneal group than in the intravenous group (hazard ratio, 0.76; 95 percent confidence interval, 0.61 to 0.96; P = 0.02). Moderate-to-severe tinnitus, clinical hearing loss, and neuromuscular toxic effects were significantly more frequent in the intravenous group.
Conclusions. As compared with intravenous cisplatin, intraperitoneal cisplatin significantly improves survival and has significantly fewer toxic effects in patients with stage III ovarian cancer and residual tumor masses of 2 cm or less. (N Engl J Med 1996;335:1950-5.)
From the University of Arizona, Tucson (D.S.A.); the Southwest Oncology Group Statistical Center, Seattle (P.Y.L.); the University of Texas Medical Branch at Galveston, Galveston (E.V.H.); Ohio State University Health Center, Columbus (R.O.); the Gynecologic Oncology Group, Philadelphia (S.D.W., D.L.C.-P., B.D., M.D.A., W.J.H.); Indiana University School of Medicine, Indianapolis (S.D.W.); the Eastern Cooperative Oncology Group, Boston (J.A.Y.); Cancer Care Associates, Tulsa, Okla. (J.A.Y.); Atlanta Regional Community Clinical Oncology Program, Atlanta (E.W.F.); Wayne State University Medical Center, Detroit (V.K.M.); and the University of Rochester Medical School, Rochester, N.Y. (B.D.). Address reprint requests to Dr. Alberts at the Southwest Oncology Group (SWOG-8501), Operations Office, 14980 Omicron Dr., San Antonio, TX 78245-3217.