An Outpatient Phase II Study of Subcutaneous Interleukin-2 and Interferon-Alpha-2b in Combination with Intravenous Vinblastine in Metastatic Renal Cell Cancer

Abstract

A prospective phase II trial was carried out to define the activity of a low-dose subcutaneous regimen of interleukin-2 (IL-2) and interferon α-2b (IFN-α) in combination with intravenous administration of vinblastine (VLB) in patients with metastatic renal cell cancer (RCC). Thirty-one patients with advanced RCC who had received no prior biochemotherapy were treated with IL-2 4.5 MU × 2/24 h thrice weekly for 2 weeks, IFN-α 3 MU/24 h thrice weekly (alternating days) for 2 consecutive weeks and VLB 4 mg/m² every 3 weeks. Patients were to have a 1-week rest period after each 2 weeks of therapy with cytokines. Treatment was repeated every 3 weeks. Maximum duration of treatment was 1 year. Treatment was administered on an outpatient basis. There were 4 complete (12.9%) and 8 partial responses (25.8%), with an overall response rate of 38.7%. The median duration of response was 6.5 months. Responses were seen in lung, lymph nodes, bones, liver and other tumor metastases. Toxicity was mild to moderate, consisting of fever, anorexia, malaise and nausea-vomiting in >80% of patients. Hypotension and transient alopecia occurred in >20% of patients. Liver enzyme elevation was frequently observed. Treatment-induced eosinophilia occurred in the majority of patients, while in 52% of patients granulocytopenia grade II and grade III did not require dose modification of drugs. Transient inflammation and local induration at the injection sites was observed in the majority of patients. None of the patients experienced major VLB-related toxicity and no toxic deaths occurred. This three-drug combination immunochemotherapy may be a promising regimen with modest toxicity in advanced RCC.

Dual Therapeutic Efficacy of Vinblastine as a Unique Chemotherapeutic Agent Capable of Inducing Dendritic Cell Maturation

“…Combination of VBL with additional immuno-stimulating agent(s) may produce markedly improved outcomes. In fact, VBL has been combined with IL-2 and/or interferon-α for the treatment of advanced cancer patients (39, 40). …”

Renal cell carcinoma with intramyocardial metastases

“…Between September 2003 and January 2004, the patient received two courses of immunochemotherapy with a regimen of vinblastine, interleukin-2, and interferon alpha-2a (IFN-α-2a) in a single dosage of 4 mg intravenous vinblastine per m 2 of body surface, 4.5 MU/m 2 subcutaneous interleukin-2 q12h, qw1,3,5 and 3 MU/m 2 subcutaneous interferon alpha-2a qd, qw 2,4,6 [27]. The immunochemotherapy was terminated due to stenocardial chest pain without myocardial ischemia signs.…”

Cellular Impedance Assays for Predictive Preclinical Drug Screening of Kinase Inhibitor Cardiovascular Toxicity

“…Approximately one third of patients administered paclitaxel, used to treat a broad range of cancers, display cardiac dysfunction including hypotension, arrhythmias, and chronic heart failure (Floyd et al, 2005;Rowinsky and Donehower, 1995). Vinblastine, also used to treat several cancers, has been shown to cause cardiac ischemia (Senkus and Jassem, 2011) and hypotension when administered in combination with other chemotherapeutics (Pectasides et al, 1998;Schiller, 1996). Colchicine, used as an immunosuppressant and for the treatment of gout, has been shown to cause cardiac dysfunction including hypotension and arrhythmias (Finkelstein et al, 2010;Sussman et al, 2004).…”