Phase II study of irinotecan in prior chemotherapy-treated squamous cell carcinoma of the cervix

Purpose: A phase II study was performed to evaluate the antitumor activity and toxicity of irinotecan (CPT-11), a water-soluble derivative of camptothecin, in patients with prior chemotherapy treated squamous cell cancer of the cervix. Patients and Methods: Forty-two patients were included in the study. The median age was 44 years (range, 24 to 59 years). The median Zubrod performance status was 1. All patients were refractory to first-line chemotherapy and 88% had received prior radiotherapy. The initial dose of CPT-11 was 125 mg/m² given as a weekly 90-minute intravenous infusion for 4 weeks, every 6 weeks. Subsequent doses were unchanged, reduced, or omitted according to toxicity grade. Results: Forty-two patients were assessable for response. The overall response rate was 21%. The median time to response was 6 weeks and the median duration of response was 12 weeks. The overall median duration of survival was 6.4 months. A statistically significant survival advantage (median of 12.6 v 5.1 months) was found in patients whose disease responded to the treatment (P < .015). The major dose-limiting toxic effects (grade ≤ 3) were nausea and vomiting (45%), diarrhea (24%), and granulocytopenia (36%). Grade ≤ 3 anemia was encountered in 62% of patients and the incidence of thrombocytopenia was negligible. Less severe side effects were alopecia (48%), drug fever (43%), anorexia (33%), fatigue (33%), skin rash (21%), stomatitis (14%), and allergic reaction (9%). The gastrointestinal intolerance was dose-related. The incidence of bone marrow depression did not decrease with dose reduction, possibly because of a cumulative effect or hematologic intolerance by a subset of patients. Conclusions: CPT-11 has significant activity in refractory cervical carcinoma. Gastrointestinal intolerance and hematologic toxicity must be monitored carefully. Further studies of alternative schedules may improve the tolerance and response rate.