title: Phase II trial of irinotecan (CPT-11) in relapsed or refractory non-Hodgkin's lymphomas.
abstract: 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 II trial with escalated doses.
  
  
  METHODS
  From 04/98 to 05/01, 28 patients with NHL were enrolled.
  
  
  METHODS
  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 II study and 8 patients were previously treated with high-dose therapy and stem-cell transplantation. CPT11 was administrated at the doses of 350 mg/m2 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 II or more toxicity was observed after the first course, escalated dose (500 mg/m2) 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/m2). 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 I/IV neutropenia occurred withoutother major toxicity.
  
  
  CONCLUSIONS
  CPT11 has low activity in heavily pretreated NHLs. Responses were of short duration.
authors.affiliation: Department de Médecine, Institut Gustave-Roussy, 39 Rue C Desmoulins, 94805 Villejuif, France. ribrag@igr.fr
authors.forename: V
authors.initials: V
authors.lastname: Ribrag
authors.forename: S
authors.initials: S
authors.lastname: Koscielny
authors.forename: J M
authors.initials: JM
authors.lastname: Vantelon
authors.forename: C
authors.initials: C
authors.lastname: Fermé
authors.forename: K
authors.initials: K
authors.lastname: Rideller
authors.forename: P
authors.initials: P
authors.lastname: Carde
authors.forename: J H
authors.initials: JH
authors.lastname: Bourhis
authors.forename: J N
authors.initials: JN
authors.lastname: Munck
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D002166:Camptothecin / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D017322:Clinical Trials, Phase II as Topic; D003967:Diarrhea / Q000139:chemically induced / Q000517:prevention & control; D019008:Drug Resistance, Neoplasm; D004791:Enzyme Inhibitors / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D005260:Female; D006801:Humans; D000077146:Irinotecan; D015993:Life Tables; D008228:Lymphoma, Non-Hodgkin / Q000188:drug therapy* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors; D009503:Neutropenia / Q000139:chemically induced; D012008:Recurrence; D016879:Salvage Therapy; D016019:Survival Analysis; D059004:Topoisomerase I Inhibitors; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D004791:Enzyme Inhibitors; D009363:Neoplasm Proteins; D059004:Topoisomerase I Inhibitors; D000077146:Irinotecan; D002166:Camptothecin