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[Intraarterial chemotherapy for metastatic renal cell carcinomas: combination with MDR-overcoming agents]
Abstract:
We analyzed the sensitizing activity of five agents, which have been assumed to be MDR-overcoming drugs, in two human renal cell carcinoma cell lines expressing the MDR1 gene at high levels. In addition, we studied the sensitizing activity of cepharanthin, an MDR-overcoming agents, to vinblastine, adriamycin, epirubicin, cisplatin, mitomycin C and etoposide. Based on the results, we treated 6 patients with metastatic renal cell carcinomas (4: bones, 2: contralateral kidneys) by intraarterial injection of vinblastine and adriamycin (or epirubicin) in combination with cepharanthin. Two of the 4 bone metastasis cases responded markedly to the treatment. Renal tubular impairment was observed in one patient who was treated for the contralateral kidney metastasis.
Insights
This study investigated cepharanthin as a multidrug resistance (MDR)-overcoming drug in renal cell carcinoma. Cepharanthin showed promise in treating bone metastases, with some patients responding markedly to the combination therapy.
Area of Science:
- Oncology
- Pharmacology
- Molecular Biology
Background:
- Multidrug resistance (MDR) is a major challenge in cancer chemotherapy.
- The MDR1 gene and its P-glycoprotein (P-gp) efflux pump are key mechanisms of MDR.
- Identifying MDR-overcoming agents is crucial for improving treatment efficacy.
Purpose of the Study:
- To evaluate the MDR-overcoming potential of five agents, including cepharanthin, in human renal cell carcinoma (RCC) cell lines.
- To assess the sensitizing activity of cepharanthin in combination with various chemotherapeutic agents.
- To investigate the clinical efficacy and safety of cepharanthin-based combination therapy in patients with metastatic RCC.
Main Methods:
- In vitro analysis of MDR-overcoming agents in high MDR1-expressing human RCC cell lines.
- Assessment of cepharanthin's sensitizing effects on vinblastine, adriamycin, epirubicin, cisplatin, mitomycin C, and etoposide.
- Intraarterial administration of vinblastine/adriamycin (or epirubicin) plus cepharanthin in 6 patients with metastatic RCC.
Main Results:
- Cepharanthin demonstrated sensitizing activity in MDR1-overexpressing RCC cell lines.
- Two out of four patients with bone metastases showed a marked response to the combination therapy.
- One patient experienced renal tubular impairment during treatment for contralateral kidney metastasis.
Conclusions:
- Cepharanthin exhibits potential as an MDR-overcoming agent in renal cell carcinoma.
- Combination therapy with cepharanthin may be effective for treating bone metastases in RCC.
- Further investigation is warranted to optimize the use and assess the safety profile of cepharanthin in RCC treatment.