Gemcitabine/capecitabine in patients with metastatic breast cancer pretreated with anthracyclines and taxanes.
OBJECTIVE
Gemcitabine and capecitabine are 2 anticancer drugs with a mechanism of action involving metabolism of pyrimidine nucleotides. Both are among the few agents active in patients with metastatic breast cancer (MBC) progressing after therapy with anthracyclines and taxanes. We have conducted a phase II trial of gemcitabine/capecitabine in patients with disease progression after treatment with anthracyclines and taxanes.


METHODS
Treatment included gemcitabine 2000 mg/m2 on day 1 every 3 weeks and capecitabine 2500 mg/m2 daily (divided into 2 doses) on days 1-14 every 3 weeks; treatment was administered until disease progression or unacceptable toxicity was documented. All patients received concomitant oral pyridoxine 300 mg twice daily to prevent hand-foot syndrome (HFS). Of 39 patients treated, 33 had received previous treatment with anthracyclines, 6 had medical contraindication to anthracyclines, 35 had previously received taxanes, and 23 had received vinorelbine. Fourteen patients had previous high-dose chemotherapy with stem cell rescue and 5 had previously received trastuzumab. Patients were 31-79 years of age (median, 55 years) and, altogether, were given 386 courses of therapy (range, 1-36 courses per patient; median, 6 courses).


RESULTS
Grade 3/4 toxicities included HFS (11 courses, 6 patients), stomatitis (6 courses, 2 patients), diarrhea (5 courses, 4 patients), anemia (5 courses, 2 patients), thrombocytopenia (5 courses, 2 patients), and neutropenia (1 course, 1 patient). Response rate (all 39 patients were evaluable) was 48.7% (partial response, n = 19; stable disease, n = 7; progressive disease, n = 13). Thirty-six patients died because of disease progression, and 3 are alive with progressive disease. Median follow-up was 26 months or until death. Median duration of response was 15 months (range, 3-26 months). Median time to disease progression was 5 months (range, 1-26 months). Median overall survival duration was 10 months (range, 1-37 months).


CONCLUSIONS
In this cohort of patients heavily pretreated with anthracyclines and taxanes, the response rate to gemcitabine/capecitabine is encouraging, although response duration is limited.
Andres
Raquel
R
Division of Medical Oncology, Hospital Clinico Universitario, Zaragoza, Spain.
Mayordomo
Jose Ignacio
JI
Lara
Ricardo
R
Lastra
Rodrigo
R
Ortega
Eugenia
E
Polo
Eduardo
E
Lambea
Julio
J
Isla
Dolores
D
Saenz-Cusi
Alberto
A
Escudero
Pilar
P
Tres
Alejandro
A
D000328:Adult; D000368:Aged; D018943:Anthracyclines / Q000494:pharmacology / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D000069287:Capecitabine; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D018450:Disease Progression; D019008:Drug Resistance, Neoplasm; D005260:Female; D005472:Fluorouracil / Q000031:analogs & derivatives; D006801:Humans; D007262:Infusions, Intravenous; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy; D043823:Taxoids / Q000494:pharmacology / Q000627:therapeutic use; D016896:Treatment Outcome; D000093542:Gemcitabine
D018943:Anthracyclines; D043823:Taxoids; D003841:Deoxycytidine; D000069287:Capecitabine; D005472:Fluorouracil; D000093542:Gemcitabine