Irinotecan plus carboplatin versus oral etoposide plus carboplatin in extensive small-cell lung cancer:: A Randomized phase III trial

被引:132
作者
Hermes, Andreas [1 ]
Bergman, Bengt
Bremnes, Roy
Ek, Lars
Fluge, Sverre
Sederholm, Christer
Sundstrom, Stein
Thaning, Lars
Vilsvik, Jan
Aasebo, Ulf
Soerenson, Sverre
机构
[1] Grosshansdorf Hosp, Dept Pulm Oncol, D-22927 Grosshansdorf, Germany
关键词
D O I
10.1200/JCO.2007.15.7545
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Purpose A Japanese randomized trial showed superior survival for patients with extensive-disease (ED) small-cell lung cancer (SCLC) receiving irinotecan plus cisplatin compared with etoposide plus cisplatin. The present trial evaluated the efficacy of irinotecan plus carboplatin (IC) compared with oral etoposide plus carboplatin (EC). Patients and Methods Patients with ED SCLC were randomly assigned to receive either IC, which consisted of carboplatin (area under the curve = 4; Chatelut formula) and irinotecan (175 mg/m(2)) intravenously both on day 1, or EC, which consisted of carboplatin as in IC and etoposide (120 mg/m(2)/d) orally on days 1 through 5. Courses were repeated every 3 weeks with four cycles planned. Doses were reduced by one third in patients with a WHO performance status (PS) of 3 to 4 and/or age older than 70 years. Primary end point was overall survival (OS). Secondary end points were quality of life (QOL) and complete response (CR) rate. Results Of 220 randomly assigned patients, 209 were eligible for analysis (IC, n = 105; EC, n = 104). Thirty-five percent were older than 70 years, and 47% had a PS of 2 to 4. The groups were well balanced with respect to prognostic factors. OS was inferior in the EC group (hazard ratio = 1.41; 95% CI, 1.06 to 1.87; P = .02). Median survival time was 8.5 months for IC compared with 7.1 months for EC. One-year survival rate was 34% for IC and 24% for EC. CR was seen in 18 IC patients compared with seven EC patients (P = .02). There were no statistically significant differences in hematologic grade 3 or 4 toxicity. Grade 3 or 4 diarrhea was more common in the IC group. QOL differences were small, with a trend toward prolonged palliation with the IC regimen. Conclusion IC prolongs survival in ED SCLC with slightly better scores for QOL.
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页码:4261 / 4267
页数:7
相关论文
共 20 条
[1]   THE EUROPEAN-ORGANIZATION-FOR-RESEARCH-AND-TREATMENT-OF-CANCER QLQ-C30 - A QUALITY-OF-LIFE INSTRUMENT FOR USE IN INTERNATIONAL CLINICAL-TRIALS IN ONCOLOGY [J].
AARONSON, NK ;
AHMEDZAI, S ;
BERGMAN, B ;
BULLINGER, M ;
CULL, A ;
DUEZ, NJ ;
FILIBERTI, A ;
FLECHTNER, H ;
FLEISHMAN, SB ;
DEHAES, JCJM ;
KAASA, S ;
KLEE, M ;
OSOBA, D ;
RAZAVI, D ;
ROFE, PB ;
SCHRAUB, S ;
SNEEUW, K ;
SULLIVAN, M ;
TAKEDA, F .
JOURNAL OF THE NATIONAL CANCER INSTITUTE, 1993, 85 (05) :365-376
[2]  
BERGMAN B, 1987, EUR J RESPIR DIS, V70, P49
[3]   THE EORTC QLQ-LC13 - A MODULAR SUPPLEMENT TO THE EORTC CORE QUALITY-OF-LIFE QUESTIONNAIRE (QLQ-C30) FOR USE IN LUNG-CANCER CLINICAL-TRIALS [J].
BERGMAN, B ;
AARONSON, NK ;
AHMEDZAI, S ;
KAASA, S ;
SULLIVAN, M .
EUROPEAN JOURNAL OF CANCER, 1994, 30A (05) :635-642
[4]   TRIMETHOPRIM SULFAMETHOXAZOLE VERSUS PLACEBO - A DOUBLE-BLIND COMPARISON OF INFECTION PROPHYLAXIS IN PATIENTS WITH SMALL CELL-CARCINOMA OF THE LUNG [J].
DEJONGH, CA ;
WADE, JC ;
FINLEY, RS ;
JOSHI, JH ;
AISNER, J ;
WIERNIK, PH ;
SCHIMPFF, SC .
JOURNAL OF CLINICAL ONCOLOGY, 1983, 1 (05) :302-307
[5]  
Hande K, 1999, CLIN CANCER RES, V5, P2742
[6]   Randomized phase III trial comparing irinotecan/cisplatin with etoposide/cisplatin in patients with previously untreated extensive-stage disease small-cell lung cancer [J].
Hanna, N ;
Bunn, PA ;
Langer, C ;
Einhorn, L ;
Guthrie, T ;
Beck, T ;
Ansar, R ;
Ellis, P ;
Byrne, M ;
Morrison, M ;
Hariharan, S ;
Wang, B ;
Sandler, A .
JOURNAL OF CLINICAL ONCOLOGY, 2006, 24 (13) :2038-2043
[7]   THE SUPERIORITY OF COMBINATION CHEMOTHERAPY INCLUDING ETOPOSIDE BASED ON INVIVO CELL-CYCLE ANALYSIS IN THE TREATMENT OF EXTENSIVE SMALL-CELL LUNG-CANCER - A RANDOMIZED TRIAL OF 288 CONSECUTIVE PATIENTS [J].
HIRSCH, FR ;
HANSEN, HH ;
HANSEN, M ;
OSTERLIND, K ;
VINDELOV, LL ;
DOMBERNOWSKY, P ;
SORENSSON, S .
JOURNAL OF CLINICAL ONCOLOGY, 1987, 5 (04) :585-591
[8]   Phase II study of irinotecan combined with carboplatin in previously untreated small-cell lung cancer [J].
Kinoshita, A ;
Fukuda, M ;
Soda, H ;
Nagashima, S ;
Fukuda, M ;
Takatani, H ;
Kuba, M ;
Nakamura, Y ;
Tsurutani, J ;
Kohno, S ;
Oka, M .
BRITISH JOURNAL OF CANCER, 2006, 94 (09) :1267-1271
[9]   Pharmacokinetic comparison of oral and intravenous etoposide in patients treated with the CHOEP-regimen for malignant lymphomas [J].
Kroschinsky, Frank P. ;
Friedrichsen, Kai ;
Mueller, Juliane ;
Pursche, Stefan ;
Haenel, Mathias ;
Prondzinsky, Roland ;
Ehninger, Gerhard ;
Schleyer, Eberhard .
CANCER CHEMOTHERAPY AND PHARMACOLOGY, 2008, 61 (05) :785-790
[10]  
Lassen U, 1996, ANN ONCOL, V7, P365