A phase I study of 5-fluorouracil, leucovorin and levamisole

被引:5
作者
Cleary, JF [1 ]
Arzoomanian, R [1 ]
Alberti, D [1 ]
Feierabend, C [1 ]
Storer, B [1 ]
Witt, P [1 ]
Carbone, P [1 ]
Wilding, G [1 ]
机构
[1] MED COLL WISCONSIN,MILWAUKEE,WI 53226
关键词
5; fluorouracil; leucovorin; levamisole; phase; 1; toxicity;
D O I
10.1007/s002800050576
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Purpose: The activity of 5-fluorouracil (5-FU) against colon cancer is enhanced by leucovorin and the combination of 5-FU and levamisole has activity in the adjuvant treatment of colonic malignancies. The combination of 5-FU with both leucovorin and levamisole may provide additional benefit in the treatment of colon cancer. Methods: A phase I study to assess qualitative and quantitative toxicities of this three-drug combination and to determine a dose for further phase II testing was undertaken. The role of levamisole as an immunomodulator was also assessed. Results: A group of 38 patients with incurable metastatic malignancies received 119 cycles of treatment at eight dose levels. 5-FU (375 mg/m(2) per day) and leucovorin (200 mg/m(2) per day) were administered intravenously (days 1-5). Levamisole was administered orally (days 1-3 and 15-17) at doses from 30 to 470 mg/m(2) per day. Patients received both SFU/leucovorin and 5-FU/leucovorin/levamisole in random order for their initial two cycles. All subsequent treatments were with the three-drug combination. Toxicities included nausea, vomiting, stomatitis, thrombocytopenia and granulocytopenia. Diarrhea was the dose-limiting toxicity at 470 mg/m(2) per day levamisole. The addition of levamisole resulted in more toxicity than 5-FU and leucovorin alone. No clinical responses were seen with this regimen. The addition of levamisole resulted in more immunomodulation than 5-FU and leucovorin alone as evidenced by release of neopterin from monocytes. Conclusion: With this schedule and dose of 5-FU and leucovorin, the maximum tolerated dose of levamisole was 354 mg/m(2) However, given the lack of response and the absence of dose-dependent immunomodulation, this may not be the appropriate dose for further phase 11 studies.
引用
收藏
页码:300 / 306
页数:7
相关论文
共 32 条
[1]   A PHASE-II TRIAL OF 5-FLUOROURACIL AND HIGH-DOSE INTRAVENOUS LEUCOVORIN IN GASTRIC-CARCINOMA [J].
ARBUCK, SG ;
DOUGLASS, HO ;
TRAVE, F ;
MILLIRON, S ;
BARONI, M ;
NAVA, H ;
EMRICH, LJ ;
RUSTUM, YM .
JOURNAL OF CLINICAL ONCOLOGY, 1987, 5 (08) :1150-1156
[2]  
BARTL R, 1991, CANCER, V68, P2241, DOI 10.1002/1097-0142(19911115)68:10<2241::AID-CNCR2820681024>3.0.CO
[3]  
2-0
[4]  
Belle H. V., 1976, CLIN CHEM, V22, P972
[5]   HIGH-DOSE CONTINUOUS INFUSION FOLINIC ACID AND BOLUS 5-FLUOROURACIL IN PATIENTS WITH ADVANCED COLORECTAL-CANCER - A PHASE-II STUDY [J].
BERTRAND, M ;
DOROSHOW, JH ;
MULTHAUF, P ;
BLAYNEY, DW ;
CARR, BI ;
CECCHI, G ;
GOLDBERG, D ;
LEONG, L ;
MARGOLIN, K ;
METTER, G ;
STAPLES, R .
JOURNAL OF CLINICAL ONCOLOGY, 1986, 4 (07) :1058-1061
[6]  
BRUCKNER HW, 1991, SEMIN ONCOL, V18, P443
[7]   ADJUVANT 5-FLUOROURACIL PLUS LEVAMISOLE IN COLON-CANCER - THE PLOT THICKENS [J].
CASSIDY, J .
BRITISH JOURNAL OF CANCER, 1994, 69 (06) :986-987
[8]   LATE MORTALITY AND LEVAMISOLE ADJUVANT THERAPY IN COLORECTAL [J].
CHLEBOWSKI, RT ;
LILLINGTON, L ;
NYSTROM, JS ;
SAYRE, J .
BRITISH JOURNAL OF CANCER, 1994, 69 (06) :1094-1097
[9]   SERUM BETA-2-MICROGLOBULIN AND C-REACTIVE PROTEIN CONCENTRATIONS IN VIRAL-INFECTIONS [J].
COOPER, EH ;
FORBES, MA ;
HAMBLING, MH .
JOURNAL OF CLINICAL PATHOLOGY, 1984, 37 (10) :1140-1143
[10]   A RANDOMIZED TRIAL OF FLUOROURACIL AND FOLINIC ACID IN PATIENTS WITH METASTATIC COLORECTAL-CARCINOMA [J].
ERLICHMAN, C ;
FINE, S ;
WONG, A ;
ELHAKIM, T .
JOURNAL OF CLINICAL ONCOLOGY, 1988, 6 (03) :469-475