Vinblastine and Interferon-Gamma Combination with and without 13-Cis Retinoic Acid for Patients with Advanced Renal Cell Carcinoma

Abstract

Background: The aim of this study is firstly to determine the response rates and toxicity of two regimens containing vinblastine (VBL) in combination with interferon-gamma (IFN-γ) 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-γ 100 µg 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% CI, 6.8–18.3, range 0.59–42.49) and the median time to progression was 3.21 months (95% CI, 1.7–4.7, range 0.03–42.49). In Trial 2, the median survival was 9.54 months (95% CI, 5.9–13.1, range 0.43–24.1) and the median time to progression was 3.9 months (95% CI, 0.8–7, 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-γ does not enhance the low response of VBL-based chemotherapy. The additional administration of 13-CRA with the combination of VBL and IFN-γ 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.

Emerging Role of Rexinoids in Non-Small Cell Lung Cancer: Focus on Bexarotene

“…Recently, however, Vaishampayan et al [49] reported that this combination had only minimal activity in advanced renal cell carcinoma. Further, the addition of 13-cis-RA to vinblastine and interferon gamma did not appear to increase the efficacy of this combination in renal cell carcinoma, a highly chemoresistant tumor [50]. Clearly, 13-cis-RA has potential for the treatment of advanced cancers.…”

Synergistic effect of survivin-specific small interfering RNA and topotecan in renal cancer cells: topotecan enhances liposome-mediated transfection by increasing cellular uptake

“…Conventional cytotoxic chemotherapy and radiotherapy are largely ineffective (3), response rates to interferon (IFN)-• and IFN-ß treatments range from 10 to 20% (4), and long-lasting responses to interleukin (IL)-2-based therapy are obtained in only 4-5% of the treated patients (5). Although there have been numerous attempts to increase these low response rates by using combination therapies, such as vinblastine and IFNs, the reported effects have not been dramatic (6,7). Further improvement awaits the development of a more effective systemic therapy.…”