Phase II evaluation of paclitaxel, α-interferon, and cis-retinoic acid in advanced renal cell carcinoma

BACKGROUND. Interferon and 13-cis-retinoic acid (13-CRA) therapy showed clinical response rates of 30% in advanced renal cell carcinoma (RCC). This combination also enhanced sensitivity to paclitaxel in a bcl-2 and mutant p53 expressing renal carcinoma cell line. Based on this, the authors conducted a Phase II clinical trial of the combination of interferon, 13-CRA, and weekly paclitaxel, in advanced RCC. METHODS. The eligibility criteria consisted of unresectable or metastatic RCC, measurable disease, a Southwest Oncology Group performance status of 0-2, and adequate bone marrow, hepatic, and renal function. Prior cytotoxic or immunologic treatment including interferon was permitted. Paclitaxel was administered at a dose of 80 mg/m² as a 1-hour intravenous infusion on Days 1, 8, and 15 of each 28-day cycle. Interferon was administered at a dose of 3 million units subcutaneously daily and 13-CRA at 1 mg/kg/day orally in 2 divided doses for the first 21 days of each cycle. RESULTS. Twenty-one patients were enrolled with a median age of 52 years, 16 males and 5 females, 10 patients with no prior therapy, 5 each with prior interleukin-2 or interferon therapy, and 1 patient with both. Four patients had also received prior investigational chemotherapy. A total of 61 cycles were administered with a median of 2 per patient. Grade 3 and 4 toxicities were neutropenia in three patients, anemia in four patients, and asthenia, skin rash, and hypersensitivity reaction in one case each. Of the 20 evaluable patients, one objective partial response was observed for a duration of 7+ months. Seven patients had disease stabilization. The median survival of the entire population was 9.5 months (range, 4-18+ months). CONCLUSIONS. The combination of 13-CRA, interferon, and weekly paclitaxel was well tolerated and had minimal efficacy in advanced RCC.