Secondary drug resistance in breast cancer: failure to reverse with oral nifedipine.
We tested the efficacy of nifedipine to reverse acquired resistance to chemotherapy regimens containing doxorubicin or vinblastine or both in 12 patients with metastatic breast cancer. All patients had been receiving one or both of these drugs, had had a prior partial response (median duration 5 months, range 2-10) and subsequently progressed. Immediately after drug resistance was documented by tumor progression, eligible patients with measurable or evaluable disease were treated with nifedipine beginning 3 days before restarting the same chemotherapy. The initial dose of nifedipine was 20 mg TID, escalating daily to 40 mg TID on day 3 if the patient had no serious side effects. Nifedipine was continued at the highest tolerable dose during and for 2 days after completion of the chemotherapy. Most patients had < or = 2 prior chemotherapy regimens and a median Zubrod performance status of 1. Twelve patients received a total of 23 courses preceded by nifedipine. No objective tumor responses were observed. The expected toxic effects attributable to nifedipine occurred, but nifedipine did not increase the toxicity caused by the chemotherapy. Nifedipine, given in this dose and schedule, did not reverse acquired drug resistance in patients with breast cancer.
Holmes
F A
FA
Department of Breast Medical Oncology, The University of Texas M.D. Anderson Cancer Center, Houston, USA. faholmes@swbell.net
Lopez
A
A
Mavligit
G
G
Fraschini
G
G
Frye
D
D
Hortobagyi
G N
GN
D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000903:Antibiotics, Antineoplastic / Q000627:therapeutic use; D000972:Antineoplastic Agents, Phytogenic / Q000627:therapeutic use; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000556:secondary; D002121:Calcium Channel Blockers / Q000009:adverse effects / Q000627:therapeutic use*; D004317:Doxorubicin / Q000627:therapeutic use; D019008:Drug Resistance, Neoplasm; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D008875:Middle Aged; D009543:Nifedipine / Q000009:adverse effects / Q000627:therapeutic use*; D014747:Vinblastine / Q000627:therapeutic use
D000903:Antibiotics, Antineoplastic; D000972:Antineoplastic Agents, Phytogenic; D002121:Calcium Channel Blockers; D014747:Vinblastine; D004317:Doxorubicin; D009543:Nifedipine