Phase I study of the combination of irinotecan hydrochloride, carboplatin, and dexamethasone for the treatment of relapsed or refractory malignant lymphoma.

A phase I study of irinotecan hydrochloride (CPT-11), carboplatin, and dexamethasone treatment in 7 patients with relapsed lymphoma and 7 patients with refractory lymphoma was conducted to evaluate the maximal tolerated dose. The 6 female and 8 male patients had a median age of 63 years (range, 45-73 years), a median performance status of 0 (range, 0-2), and a median disease stage of IV. This study included patients with diffuse large B-cell lymphoma (n = 5), adult T-cell leukemia/lymphoma (n = 2), mantle cell lymphoma (n = 2), follicular lymphoma (n = 2), angioimmunoblastic T-cell lymphoma (n = 1), anaplastic large cell lymphoma (n = 1), and Hodgkin's lymphoma (n = 1). All patients had received anthracycline-containing combination chemotherapy prior to this therapy. The starting dosage of CPT-11 was 15 mg/m2 per day (days 1-3 and 8-10), and dosage-escalation increments of 5 mg/m2 per day were planned, with fixed dosages of carboplatin (250 mg/m2 per day, day 1) and dexamethasone (40 mg/body, days 1-3 and days 8-10). Five patients were enrolled at level 1, 3 at level 2, 4 at level 3, and 2 at level 4. Ten patients (71%) and 11 patients (79%) experienced grade 3 or 4 hematologic toxicities of leukocytopenia and neutropenia, respectively. Three patients (29%) and 9 patients (64%) experienced grade 3 or 4 thrombocytopenia and anemia, respectively. Two patients who received 30 mg/m2 (level 4) of CPT-11 developed sepsis. We concluded that the recommended dose of CPT-11 with carboplatin and dexamethasone is 25 mg/m2. No deaths were related to this chemotherapy, and no patient developed liver dysfunction. The overall response rate was 36%. We conclude that the combination therapy of CPT-11, carboplatin, and dexamthasone is effective as salvage therapy but that the duration of response is too short.