A RANDOMIZED TRIAL OF 2 DOSE LEVELS OF CYCLOPHOSPHAMIDE, METHOTREXATE, AND FLUOROURACIL CHEMOTHERAPY FOR PATIENTS WITH METASTATIC BREAST-CANCER

被引:329
作者
TANNOCK, IF [1 ]
BOYD, NF [1 ]
DEBOER, G [1 ]
ERLICHMAN, C [1 ]
FINE, S [1 ]
LAROCQUE, G [1 ]
MAYERS, C [1 ]
PERRAULT, D [1 ]
SUTHERLAND, H [1 ]
机构
[1] UNIV TORONTO, PRINCESS MARGARET HOSP, DEPT MED, 500 SHERBOURNE ST, TORONTO M4X 1K9, ONTARIO, CANADA
关键词
D O I
10.1200/JCO.1988.6.9.1377
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
This study was designed to assess the role of dosage of chemotherapy for treatment of metastatic breast cancer. One hundred thirty-three patients without prior chemotherapy for metastatic disease were randomly allocated to receive two different dose levels of cyclophosphamide (C), methotrexate (M), and flurouracil (F), administered intravenously (IV) every 3 weeks. Patients were stratified by sites of disease (visceral, bone, or soft-tissue dominant) and by interval from primary surgery to first recurrence. Doses on the higher-dose arm were 600 mg/m2 (C,F) and 40 mg/m2 (M) with escalation if possible; doses on the lower-dose arm were 300 mg/m2 (C,F) and 20 mg/m2 (M) without escalation. Patients who failed to respond to lower-dose CMF were crossed over to the higher-dose arm. Patients randomized to the higher-dose arm had longer survival measured from initiation of chemotherapy (median survival, 15.6 months v 12.8 months, P = .026 by log-rank test), but the effect of dose was of borderline significance (P .apprx. 0.12) when adjusted for a chance imbalance between the two arms in the time from first relapse to randomization, using the Cox proportional hazards model. Response rates (International Union Against Cancer [UICC] criteria) for patients with measurable disease were higher-dose arm: 16/53 (30%) and lower-dose arm: 6/53 (11%), (P = .03). Only one of 37 patients responded on crossover from the lower- to the higher-dose arm. Patients experienced more vomiting, myelosuppression, conjunctivitis, and alopecia when receiving higher doses of chemotherapy. A series of 34 linear analogue self-assessment scales was used to make detailed quality of life assessments on a subset of 49 patients. These scales confirmed greater toxicity in the immediate posttreatment period, but also a trend to improvement in general health and some disease-related indices, in patients receiving higher-dose chemotherapy. This trial suggests that better palliation is achieved by using full-dose chemothearpy.
引用
收藏
页码:1377 / 1387
页数:11
相关论文
共 35 条
[1]  
[Anonymous], 1971, Edits manual for the profile of mood states
[2]   QUALITY OF LIFE MEASUREMENT IN BREAST-CANCER PATIENTS [J].
BELL, DR ;
TANNOCK, IF ;
BOYD, NF .
BRITISH JOURNAL OF CANCER, 1985, 51 (04) :577-580
[3]  
BERETTA G, 1986, Proceedings American Society of Clinical Oncology Annual Meeting, V5, P77
[4]   CYCLIC COMBINATION CHEMOTHERAPY FOR METASTATIC BREAST-CANCER - COMPARISON OF 2 CMF SCHEDULES [J].
BIRAN, S ;
BRUFMAN, G .
ONCOLOGY, 1981, 38 (05) :257-259
[5]  
CANELLOS GP, 1976, CANCER-AM CANCER SOC, V38, P1882, DOI 10.1002/1097-0142(197611)38:5<1882::AID-CNCR2820380503>3.0.CO
[6]  
2-H
[7]  
CARMO-PEREIRA J, 1986, Proceedings American Society of Clinical Oncology Annual Meeting, V5, P56
[8]  
CARTER SK, 1985, J CLIN ONCOL, V3, P889
[9]   IMPROVING THE QUALITY-OF-LIFE DURING CHEMOTHERAPY FOR ADVANCED BREAST-CANCER - A COMPARISON OF INTERMITTENT AND CONTINUOUS TREATMENT STRATEGIES [J].
COATES, A ;
GEBSKI, V ;
BISHOP, JF ;
JEAL, PN ;
WOODS, RL ;
SNYDER, R ;
TATTERSALL, MHN ;
BYRNE, M ;
HARVEY, V ;
GILL, G ;
SIMPSON, J ;
DRUMMOND, R ;
BROWNE, J ;
VANCOOTEN, R ;
FORBES, JF .
NEW ENGLAND JOURNAL OF MEDICINE, 1987, 317 (24) :1490-1495
[10]  
CREECH RH, 1979, CANCER, V43, P51, DOI 10.1002/1097-0142(197901)43:1<51::AID-CNCR2820430107>3.0.CO