A phase II trial of vinblastine plus dipyridamole in advanced renal cell carcinoma. A Hoosier Oncology Group Study

Area of Science:

• Oncology
• Pharmacology

Background:

• Renal cell carcinoma (RCC) often exhibits poor response to chemotherapy due to intrinsic multidrug resistance.
• Dipyridamole (DP) is known to inhibit P-glycoprotein, a key factor in multidrug resistance, showing potential for reversing resistance in vitro.
• DP dosages for in vivo use have demonstrated good tolerability.

Purpose of the Study:

• To evaluate the efficacy and safety of combining vinblastine (VLB) with dipyridamole (DP) in patients with advanced renal cell carcinoma.
• To assess the potential of DP to overcome chemotherapy resistance in this patient population.

Main Methods:

• A phase I/II study involving 15 patients with inoperable, recurrent, or metastatic renal cell carcinoma who had not received prior chemotherapy.
• Treatment consisted of VLB (0.2 mg/kg IV) combined with DP (75 mg PO q.i.d.) administered around VLB infusion.
• Courses were repeated every 3 weeks for up to 8 weeks, or until disease progression or unacceptable toxicity.

Main Results:

• The combination therapy was generally well-tolerated, with predominant toxicities including mild neurotoxicity and leukopenia.
• No objective responses were observed in any of the patients.
• Two patients achieved stable disease for extended periods (29 and 30+ months).
• Median survival was 9 months (range: 2.5-30+ months).

Conclusions:

• The combination of VLB and DP, at the tested dose and schedule, is safe for patients with advanced renal cell carcinoma.
• This specific regimen demonstrated ineffectiveness in treating advanced renal cell carcinoma.
• Further research may be needed to explore other combinations or strategies to overcome multidrug resistance in RCC.