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

被引:13
作者
Ribrag, V
Koscielny, S
Vantelon, JM
Fermé, C
Rideller, K
Carde, P
Bourhis, JH
Munck, JN
机构
[1] Inst Gustave Roussy, Dept Med, F-94805 Villejuif, France
[2] Inst Gustave Roussy, Dept Biostat, F-94805 Villejuif, France
关键词
irinotecan; chemotherapy; non-Hodgkin lymphoma; salvage therapy;
D O I
10.1080/1042819031000099643
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
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.
引用
收藏
页码:1529 / 1533
页数:5
相关论文
共 11 条
[1]   PHASE-I AND PHARMACOLOGICAL STUDIES OF THE CAMPTOTHECIN ANALOG IRINOTECAN ADMINISTERED EVERY 3 WEEKS IN CANCER-PATIENTS [J].
ABIGERGES, D ;
CHABOT, GG ;
ARMAND, JP ;
HERAIT, P ;
GOUYETTE, A ;
GANDIA, D .
JOURNAL OF CLINICAL ONCOLOGY, 1995, 13 (01) :210-221
[2]   IRINOTECAN (CPT-11) HIGH-DOSE ESCALATION USING INTENSIVE HIGH-DOSE LOPERAMIDE TO CONTROL DIARRHEA [J].
ABIGERGES, D ;
ARMAND, JP ;
CHABOT, GG ;
DACOSTA, L ;
FADEL, E ;
COTE, C ;
HERAIT, P ;
GANDIA, D .
JOURNAL OF THE NATIONAL CANCER INSTITUTE, 1994, 86 (06) :446-449
[3]  
ARMITAGE JO, 1994, SEMIN ONCOL, V21, P82
[4]  
CABANILLAS F, 1988, SEMIN HEMATOL, V25, P47
[5]   Report of an international workshop to standardize response criteria for non-Hodgkin's lymphomas [J].
Cheson, BD ;
Horning, SJ ;
Coiffier, B ;
Shipp, MA ;
Fisher, RI ;
Connors, JM ;
Lister, TA ;
Vose, J ;
Grillo-López, A ;
Hagenbeek, A ;
Cabanillas, F ;
Klippensten, D ;
Hiddemann, W ;
Castellino, R ;
Harris, NL ;
Armitage, JO ;
Carter, W ;
Hoppe, R ;
Canellos, GP .
JOURNAL OF CLINICAL ONCOLOGY, 1999, 17 (04) :1244-1253
[6]   AN EARLY PHASE-II STUDY OF CPT-11 - A NEW DERIVATIVE OF CAMPTOTHECIN, FOR THE TREATMENT OF LEUKEMIA AND LYMPHOMA [J].
OHNO, R ;
OKADA, K ;
MASAOKA, T ;
KURAMOTO, A ;
ARIMA, T ;
YOSHIDA, Y ;
ARIYOSHI, H ;
ICHIMARU, M ;
SAKAI, Y ;
OGURO, M ;
ITO, Y ;
MORISHIMA, Y ;
YOKOMAKU, S ;
OTA, K .
JOURNAL OF CLINICAL ONCOLOGY, 1990, 8 (11) :1907-1912
[7]  
OHTA K, 1994, JPN J CANC CHEMOTHER, V21, P1047
[8]   AUTOLOGOUS BONE-MARROW TRANSPLANTATION AS COMPARED WITH SALVAGE CHEMOTHERAPY IN RELAPSES OF CHEMOTHERAPY-SENSITIVE NON-HODGKINS-LYMPHOMA [J].
PHILIP, T ;
GUGLIELMI, C ;
HAGENBEEK, A ;
SOMERS, R ;
VANDERLELIE, H ;
BRON, D ;
SONNEVELD, P ;
GISSELBRECHT, C ;
CAHN, JY ;
HAROUSSEAU, JL ;
COIFFIER, B ;
BIRON, P ;
MANDELLI, F ;
CHAUVIN, F .
NEW ENGLAND JOURNAL OF MEDICINE, 1995, 333 (23) :1540-1545
[9]   PHASE-I AND PHARMACOKINETIC TRIAL OF WEEKLY CPT-11 [J].
ROTHENBERG, ML ;
KUHN, JG ;
BURRIS, HA ;
NELSON, J ;
ECKARDT, JR ;
TRISTANMORALES, M ;
HILSENBECK, SG ;
WEISS, GR ;
SMITH, LS ;
RODRIGUEZ, GI ;
ROCK, MK ;
VONHOFF, DD .
JOURNAL OF CLINICAL ONCOLOGY, 1993, 11 (11) :2194-2204
[10]  
SGIYAMA K, 2002, CANCER, V94, P594