An EORTC phase I study of capecitabine (Xeloda) in combination with fixed doses of cyclophosphamide and epirubicin (cex) as primary treatment for large operable or locally advanced/inflammatory breast cancer.
In breast cancer, chemotherapy regimens that include infusional 5-fluorouracil (5-FU) lead to high response rates, but require central venous access and pumps. To avoid these inconveniences, we substituted infusional 5-FU with capecitabine. The main objective of this study was to determine the maximum tolerated dose (MTD) of capecitabine when given in combination with fixed doses of epirubicin and cyclophosphamide (100 and 600 mg/m(2) day 1 every (q) 3 weeks) as primary treatment for large operable or locally advanced/inflammatory breast cancer without distant metastasis. Capecitabine was escalated from 750 mg/m(2) twice a day (bid) to 1250 mg/m(2) bid from day 1 to day 14 in four dose levels. Dose escalation was permitted if 0/3 or 1/6 patients experienced dose-limiting toxicity (DLT). A total of 23 patients were included and 117 courses were administered. At dose level 4, 2 of 2 patients presented DLTs defining the MTD. A high rate of capecitabine treatment modification was required with capecitabine 1050 mg/m(2) bid (dose level 3). 19 patients achieved an objective response (83%). In conclusion, we believe that capecitabine 900 mg/m(2) bid (dose level 2) is the recommended dose in combination with epirubicin 100 mg/m(2) and cyclophosphamide 600 mg/m(2). The acceptable toxicity profile and encouraging activity of this regimen warrant further evaluation.
Bonnefoi
H
H
Hôpitaux Universitaires de Genève, 30 Boulevard de la Cluse, 1211 14, Geneva, Switzerland. herve.bonnefoi@hcuge.ch
Biganzoli
L
L
Mauriac
L
L
Cufer
T
T
Schaefer
P
P
Atalay
G
G
Piccart
M
M
D000230:Adenocarcinoma / Q000188:drug therapy* / Q000473:pathology; D000293:Adolescent; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D000069287:Capecitabine; D017024:Chemotherapy, Adjuvant; D003520:Cyclophosphamide / Q000008:administration & dosage / Q000009:adverse effects; D003841:Deoxycytidine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D004305:Dose-Response Relationship, Drug; D015251:Epirubicin / Q000008:administration & dosage / Q000009:adverse effects; D005260:Female; D005472:Fluorouracil / Q000031:analogs & derivatives; D006801:Humans; D008875:Middle Aged; D010349:Patient Compliance; D016896:Treatment Outcome
D003841:Deoxycytidine; D015251:Epirubicin; D000069287:Capecitabine; D003520:Cyclophosphamide; D005472:Fluorouracil