PHASE-II STUDY OF IRINOTECAN IN THE TREATMENT OF ADVANCED COLORECTAL-CANCER IN CHEMOTHERAPY-NAIVE PATIENTS AND PATIENTS PRETREATED WITH FLUOROURACIL-BASED CHEMOTHERAPY

Purpose: To assess the efficacy of irinotecan (CPT-11) in the treatmen t of advanced colorectal cancer in both chemotherapy-naive and pretrea ted patients. Patients and Methods: Two hundred thirteen patients (age d 18 to 75 years) with metastatic colorectal cancer, World Health Orga nization (WHO) performance status less than or equal to 2, and life ex pectancy greater than or equal to 3 months were treated with CPT-11 35 0 mg/m(2) every 3 weeks. All 178 patients eligible for efficacy analys is had not received more than one prior fluorouracil (5-FU)-based chem otherapy regimen (adjuvant or palliative) and had adequate hematologic , renal, and hepatic function. Results: Primary tumor sites were the c olon (71%) and rectum (28%). Sixty-six percent of the patients had gre ater than or equal to two metastatic sites. Ninety-eight percent of th e patients had undergone previous surgery, and 77.5% had received prio r chemotherapy. Thirty-two of 178 eligible patients achieved an object ive response (four complete responses [CRs] and 28 partial responses [ PRs]; response rate, 18%; 95% confidence interval, 12.6% to 24.4%), 65 were stable, and 59 progressed. The response rate was 17.7% in the pr etreated group and 18.8% in the chemotherapy-naive group. Within the f ormer subgroup, response rates of 16.1% were reported in patients who were progressive on prior 5-FU chemotherapy and 19.1% in patients who were progressive off such treatment. The median duration of objective response (9.1 months) and median time to achievement of a response (9. 3 weeks) did not differ between chemotherapy-naive and pretreated pati ents. The most frequent adverse events were neutropenia, which develop ed in 80% of the patients, delayed diarrhea (87%), alopecia (88%), fat igue (81%), and nausea/vomiting (77%). All these adverse events were m anageable. Severe (WHO grade 3 or 4) neutropenia was only observed in 18% of the cycles, leukopenia in 11%, delayed diarrhea in 11%, and nau sea and vomiting in 3%. Development of simultaneous grade 3 or 4 neutr openia and delayed diarrhea during 4% of the cycles was the safety iss ue of greatest concern. Conclusion: CPT-11 has definite activity in th e treatment of advanced metastatic colorectal cancer both in chemother apy-naive and in pretreated patients who experienced disease progressi on on 5-FU, which suggests a lack of cross-resistance between CPT-11 a nd 5-FU. Diarrhea and neutropenia, the major toxicities of CPT-11, con tribute to the risk to develop febrile neutropenic sepsis. (C) 1997 by American Society of Clinical Oncology.