Cyclophosphamide, methotrexate and infusional 5-fluorouracil (infusional CMF) in metastatic breast cancer.
Bolus 5-fluorouracil (5-FU) is a phase-specific drug with a short plasma half-life that is used in combination with bolus cyclophosphamide and methotrexate in the treatment of breast cancer. The efficacy of 5-FU can be improved by continuous intravenous infusion using portable infusion pumps (infusional 5-FU). Infusional 5-FU, 200 mg m(-2) day(-1), in combination with standard doses of bolus cyclophosphamide and methotrexate, was evaluated in a phase I/II dose-finding study. The cyclophosphamide and methotrexate were administered in 28-day cycles as follows: cohort 1, cyclophosphamide 600 mg m(-2), days 1 and 8, and methotrexate 40 mg m(-2), day 1; cohort 2, cyclophosphamide 400 mg m(-2), days 1 and 8, and methotrexate 40 mg m(-2), day 1; cohort 3, cyclophosphamide 480 mg (m-2), days 1 and 8, and methotrexate 40 mg m(-2), day 1; cohort 4, cyclophosphamide 480 mg m(-2), days 1 and 8, and methotrexate 40 mg m(-2), days 1 and 8. Median overall survival was 10 months (range 3-21 months). Objective tumour responses were seen in 9 of 25 patients (36%, 95% CI 18-58%), including 3 of 13 patients (23%) previously treated for metastatic disease. Cohorts 1 and 4 proved to be too toxic, with five of six patients in cohort 1 and three of four in cohort 4 developing grade III/IV neutropenia. The dose intensity of cyclophosphamide achieved was as follows: cohort 1, 82%; cohort 2, 86%; cohort 3, 97%; cohort 4, 90%. Infusional 5-FU can be administered safely and is effective in combination with cyclophosphamide 480 mg m(-2), days 1 and 8, and methotrexate 40 mg m(-2), day 1, in the treatment of metastatic breast cancer.
O'Byrne
K J
KJ
Imperial Cancer Research Fund Medical Oncology Unit, The Churchill, Oxford Radcliffe Hospital, UK.
Koukourakis
M I
MI
Saunders
M P
MP
Salisbury
A J
AJ
Isaacs
R
R
Varcoe
S
S
Taylor
M
M
Ganesan
T S
TS
Harris
A L
AL
Talbot
D C
DC
D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000401:mortality; D003520:Cyclophosphamide / Q000008:administration & dosage / Q000009:adverse effects; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000009:adverse effects; D006801:Humans; D008727:Methotrexate / Q000008:administration & dosage / Q000009:adverse effects; D008875:Middle Aged; D009362:Neoplasm Metastasis
D003520:Cyclophosphamide; D005472:Fluorouracil; D008727:Methotrexate