Phase II trial of irinotecan (CPT-11) in relapsed or refractory non-Hodgkin's lymphomas

CPT11, a camptothecin analogue, is a specific DNA topoisomerase I inhibitor, with activity in tumor cell lines with MDR expression. CPT11 has a broad spectrum of activity in solid tumors (especially in colorectal, gastric and small cell lung cancers). Early reports have shown that CPT11 could be active in non-Hodgkin's lymphomas (NHL) with low-dose schedules. To further evaluate the efficacy and toxicity of CPT11 in patients with refractory or relapsed NHLs, we conducted a phase H trial with escalated doses. Patients and therapy: From 04/98 to 05/01, 28 patients with NHL were enrolled. Patients characteristics: M/F 21/7; median age: 56 years (range 28-72); Ann Arbor stage at the time of the study I/II and III/IV in 6 and 21 patients, respectively. Sixteen patients had refractory disease when they were enrolled in this phase 11 study and 8 patients were previously treated with high-dose therapy and stem-cell transplantation. CPT11 was administrated at the doses of 350 mg/m(2) every 3 weeks. Six courses were given in patients who achieved CR, PR or stable disease. Patients were evaluated every 2 courses. If no grade 11 or more toxicity was observed after the first course, escalated dose (500 mg/m(2)) was then undertaken. Results: 19/28 patients received more than 2 courses of CPT11 and were evaluated for response. Nine patients received one course of therapy because of either progressive disease (n = 6), toxicity (n = 2) or refusal (n = 1). Ten patients received escalated dose (500 mg/m(2)). Complete remission and partial was achieved in 2/19 patients, stable disease in 7/19, and progressive disease in 10/19 patients. Median duration of responses was short (3 months, range 1-8 months). Seventy-five courses were evaluated for toxicity according to the WHO criteria. Diarrhea grade 2 or 3 occurred in 9/75 courses; cholinergic syndrome grade 2 in 3/75 courses; nausea grade 3 in 7/75 courses. Hematological toxicity: leucopenia grade 3 or 4 in 21/75 courses; thrombocytopenia grade 3 in 8/75 courses; infectious episodes grade 2 or 3 in 7/75 courses. In 2/7 courses with escalated doses, grade III/IV neutropenia occurred without other major toxicity. Conclusion: CPT11 has low activity in heavily pretreated NHLs. Responses were of short duration.