title: Phase I study of the combination of irinotecan hydrochloride, carboplatin, and dexamethasone for the treatment of relapsed or refractory malignant lymphoma.
abstract: 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.
authors.affiliation: Department of Internal Medicine, Fukuoka University, School of Medicine, Nanakuma 7-45-1, Jonan-ku, Fukuoka 814-0180, Japan. junsuzu@fukuoka-u.ac.jp
authors.forename: Junji
authors.initials: J
authors.lastname: Suzumiya
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Suzushima
authors.forename: Kouichi
authors.initials: K
authors.lastname: Maeda
authors.forename: Seiichi
authors.initials: S
authors.lastname: Okamura
authors.forename: Atae
authors.initials: A
authors.lastname: Utsunomiya
authors.forename: Tunefumi
authors.initials: T
authors.lastname: Shibuya
authors.forename: Kazuo
authors.initials: K
authors.lastname: Tamura
mesh_terms: D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000633:toxicity; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives*; D016190:Carboplatin / Q000008:administration & dosage; D003907:Dexamethasone / Q000008:administration & dosage; D005260:Female; D006801:Humans; D000077146:Irinotecan; D008223:Lymphoma / Q000150:complications / Q000188:drug therapy*; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D016879:Salvage Therapy / Q000009:adverse effects / Q000379:methods*; D016896:Treatment Outcome
chemical_list: D000077146:Irinotecan; D003907:Dexamethasone; D016190:Carboplatin; D002166:Camptothecin