Primary Chemotherapy in Stage IV Ovarian Cancer. A Prospective Phase II Study

Abstract

Surgical removal of advanced ovarian cancer and associated primary lymph nodes may encourage the growth and proliferation of remaining tumor cells. This article presents the results of an investigation of 34 previously untreated women with diagnosis of stage IV ovarian cancer who underwent preoperative chemotherapy. From 1993 to 1996, 24 patients received four courses of 300 mg/m 2 carboplatin, 700 mg/ m 2 cyclophosphamide, and 60 mg/m 2 epirubicin given at 3- or 4-week intervals. After October 1996, carboplatin and cyclophosphamide were replaced with paclitaxel. Ten patients were treated with four courses of this combination. The protocol called for radical surgery after the fourth course of chemotherapy. At this point, patients who had shown a complete or partial response received an additional two courses of the same combination of drugs, and patients with stable or progressive disease were treated with other chemotherapy regimens. Twenty-eight patients showed some response to the preoperative chemotherapy (complete response in 9 patients and partial response in 19). Twenty-eight patients underwent exploratory laparotomy with hysterectomy and bilateral salpingo-oophorectomy. At the time of surgery, 9 patients had no evidence of disease. The 19 patients with a partial response had no evidence of disease after surgery. Three patients were found to have liver metastases and underwent hepatic metastasectomy followed by topotecan chemotherapy. Three patients had stable disease. Two of these women refused surgical treatment, and one, with inoperable disease, was given salvage chemotherapy. At the time of this report, with a median follow-up of 23 months, 11 of the 34 patients (32%) are alive with no evidence of disease. The initial sites of disease recurrence were the peritoneum (nine patients), lung (three patients), liver (four patients), and bone (one patient). Four women had an increase in serum cancer antigen 125 levels. The median time to recurrence of disease was 16.45 months, and the actuarial median length of survival was 28 months. The 1- and 2-year survival rates were 94% and 62%, respectively, for all patients. Hematological toxicity occurred in more than half of the courses of chemotherapy (60%), with leucopenia reaching World Health Organization toxicity grade 3 in 47% of patients and grade 4 in 12%. Neutropenia toxicity was grade 3 in 30% and grade 4 in 44% of patients. Anemia was most commonly grade 2 (41%) with no patient having grade 4 anemia. Nausea, vomiting, and diarrhea were mostly grades 1 and 2 with no grade 4 symptoms. Toxicity was severe enough to require dose reduction in one-fourth of the treatment cycles. No patient died from treatment.