Intraperitoneal Cisplatin and Paclitaxel in Ovarian Cancer

Abstract

This randomized, phase III trial by the Gynecologic Oncology Group (GOG) was designed to compare treatment with intravenous paclitaxel plus cisplatin with intravenous paclitaxel plus intraperitoneal cisplatin and paclitaxel in patients with stage III ovarian cancer. study. End points were the progression-free and overall survival. Eligibility criteria included a primary diagnosis of stage III ovarian cancer with no residual mass greater than 1.0 cm after surgical treatment, at least a moderate activity level, normal blood counts, and adequate renal and hepatic function. Patients randomized to the intravenous therapy group received 135 mg intravenous paclitaxel per square meter of body surface area over a 24-hour period on day 1 and 75 mg intravenous cisplatin per square meter on day 2. Patients in the intraperitoneal therapy group were given 135 mg intravenous paclitaxel per square meter of body surface for 24 hours followed by 100 mg intraperitoneal cisplatin per square meter on day 2 and 60 mg intraperitoneal paclitaxel per square meter on day 8. New cycles were not started until neutrophil counts were greater than 1500 cells/mm 3 , platelet counts were ≥1,000,000 cells/mm 3 , and creatinine levels were ≤2.0 mg/dL. Participants were removed from the study when new cycles were delayed for more than 3 weeks. In the intraperitoneal group, patients who experienced grade 2 abdominal pain were given lower doses of the intraperitoneal drug. Persistent grade 2 abdominal pain, or grade 3 abdominal pain, or complications involving the intraperitoneal catheter resulted in a conversion to intravenous therapy for the remaining cycles. Carboplatin replaced cisplatin if severe toxicity resulting from cisplatin developed. Of the 415 women who met all eligibility criteria, 210 were randomized to the intravenous group, and 205 were assigned to the intraperitoneal group. Ninety percent of patients in the intravenous group completed six cycles of chemotherapy, and 83% received six cycles of the assigned intravenous therapy. In comparison, 83% of women in the intraperitoneal group completed six cycles of chemotherapy, but only 42% received all six cycles of the assigned intraperitoneal therapy. Compared with the intravenous group, the intraperitoneal therapy group had significantly more grade 3 or 4 adverse events, the most severe of which were fatigue, pain, or hematologic, gastrointestinal, metabolic, or neurologic toxic effects (P ≤.001 for all). After a median follow up of 48.2 months for the intravenous group and 52.6 months for the intraperitoneal therapy group, the median progression-free survivals were 18.3 months and 23.8 months, respectively (Fig. 1). The median overall survival was 49.7 months in the intravenous group compared with 65.6 months for the intraperitoneal group (Fig. 2). Quality-of-life assessments were made at baseline, before the fourth cycle, 3 to 6 weeks after the sixth cycle, and 12 months after the sixth cycle. After adjustments for confounding factors, the patients receiving intraperitoneal therapy reported lower quality-of-life scores at the prefourth cycle assessment (P <.001) and 3 to 6 weeks after completion of therapy (P =.009) compared with the patients in the intravenous group. However, 12 months after treatment, there were no differences in quality of life between the two groups.