Vinblastine and interferon-gamma combination with and without 13-cis retinoic acid for patients with advanced renal cell carcinoma - Results of two phase II clinical trials

Background. The aim of this study is firstly to determine the response rates and toxicity of two regimens containing vinblastine (VBL) in combination with interferongamma (IFN-gamma) in the treatment of patients with advanced renal cell carcinoma (RCC), and secondly to evaluate the additional efficacy of 13-cis retinoic acid (13-CRA) in RCC. Methods: Twenty-nine patients were included in the first trial (Trial 1) and 40 in the second one (Trial 2). The therapy given in Trial 1 consisted of VBL 0.15 mg/kg i.v. every 2 weeks and IFN-gamma 100 mug s.c. 3 times weekly. In Trial 2, the therapy consisted of the same two drugs, in the same doses, plus oral 13-CRA 40 mg/day. Results: In Trial 1 there were 3 (10.3%) patients with complete response, 3 (10.3%) patients with partial response, 8 (27.6%) patients with stable disease and 15 (51.7%) patients with progressive disease. In Trial 2, there was no complete response, however, 3 (7.5%) patients had partial response. Additionally, 15 (37.5%) patients maintained stable disease and 14 (35%) patients had progressive disease. In Trial 1, the median survival was 12.56 months (95% Cl, 6.8-18.3, range 0.59-42.49) and the median time to progression was 3.21 months (95% Cl, 1.7-4.7, range 0.03-42.49). In Trial 2, the median survival was 9.54 months (95% Cl, 5.9-13.1, range 0.43-24.1) and the median time to progression was 3.9 months (95% Cl, 0.87, range 0.26-24.1). In Trial 1, granulocytopenia grade 3 and 4 appeared in 5 (17.2%) patients and anaemia grade 3 in 1 (3.4%) patient. In Trial 2, there were grade 3 toxicities, as granulocytopenia in 5 (12.5%) patients, anemia in 4 (10.0%) patients, stomatitis in 3 (7.5%) patients, fatigue/malaise in 3 (7.5%) patients and 1 (2.5%) had diarrhea. No toxic deaths occurred in both studies. Conclusion: The use of IFN-gamma does not enhance the low response of VBLbased chemotherapy. The additional administration of 13-CRA with the combination of VBL and IFN-gamma does not add to the efficacy of this combination in patients with advanced renal cell carcinoma. New active agents are needed to treat patients with this disease.