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Secondary drug resistance in breast cancer: failure to reverse with oral nifedipine
F A Holmes1, A Lopez, G Mavligit
1Department of Breast Medical Oncology, The University of Texas M.D. Anderson Cancer Center, Houston, USA. faholmes@swbell.net
Abstract:
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.
Insights
Nifedipine did not reverse acquired resistance to chemotherapy in metastatic breast cancer patients. This study found no objective tumor responses when nifedipine was added to doxorubicin or vinblastine regimens.
Area of Science:
- Oncology
- Pharmacology
Background:
- Acquired resistance to chemotherapy is a major challenge in treating metastatic breast cancer.
- Doxorubicin and vinblastine are common chemotherapy agents for breast cancer.
Purpose of the Study:
- To evaluate if nifedipine can reverse acquired resistance to doxorubicin or vinblastine in metastatic breast cancer.
- To assess the safety and efficacy of nifedipine in combination with chemotherapy.
Main Methods:
- Twelve patients with metastatic breast cancer resistant to doxorubicin/vinblastine received nifedipine before and during chemotherapy.
- Nifedipine dosage was escalated based on tolerability, with treatment continuing post-chemotherapy.
Main Results:
- No objective tumor responses were observed in any patients treated with nifedipine and chemotherapy.
- Nifedipine did not increase the toxicity of the chemotherapy regimens.
Conclusions:
- Nifedipine, at the tested dose and schedule, is ineffective in reversing acquired chemotherapy resistance in breast cancer.
- Further research may be needed to explore other strategies for overcoming drug resistance.