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Verapamil enhances antitumor activity without increasing myeloid toxicity
Surgery
|January 1, 1987
Summary
Verapamil (VER) enhances chemotherapy by increasing the effectiveness of vincristine sulfate (VCR) and 5-fluorouracil (5-FU) against tumors. This combination therapy improves survival and reduces tumor formation without increasing toxicity to bone marrow cells.
Area of Science:
- Oncology
- Pharmacology
- Cancer Research
Background:
- Chemotherapy effectiveness is often limited by drug resistance and toxicity to normal cells.
- Verapamil has shown potential in increasing the cytotoxicity of certain chemotherapy drugs in cell cultures.
- Investigating drug combinations is crucial for improving cancer treatment outcomes.
Purpose of the Study:
- To evaluate the effect of verapamil (VER) on the efficacy and toxicity of vincristine sulfate (VCR) and 5-fluorouracil (5-FU) in a murine lung colonization model.
- To determine if verapamil enhances the anti-tumor activity of VCR and 5-FU.
- To assess the impact of verapamil on the bone marrow toxicity associated with VCR and 5-FU.
Main Methods:
- An intravenous lung colonization model using B16 F10 melanoma cells in mice was established.
- Mice were randomized into groups receiving saline, verapamil, VCR, VCR plus verapamil, 5-FU, or 5-FU plus verapamil.
- Pulmonary tumor formation was quantified, and animal survival was monitored. Bone marrow toxicity was assessed using quantitative clonal culture of granulocyte-macrophage progenitor cells (GM-CFC) and in vivo assays.
Main Results:
- The addition of verapamil to vincristine sulfate significantly decreased pulmonary tumor formation and increased mean survival time.
- Verapamil combined with 5-fluorouracil also significantly reduced tumor colony formation, but did not significantly prolong survival.
- Verapamil did not significantly increase bone marrow toxicity when combined with either VCR or 5-FU, as assessed by GM-CFC growth and in vivo assays.
Conclusions:
- Verapamil enhances the oncolytic effects of both vincristine sulfate and 5-fluorouracil in this lung colonization model.
- The combination of verapamil with VCR or 5-FU did not result in increased toxicity to normal host bone marrow progenitor cells.
- Verapamil shows promise as an adjuvant therapy to improve chemotherapy efficacy without augmenting host toxicity.