Background. Treatment with interleukin‐2 (IL‐2) and lymphokine‐activated killer cells (LAK) resulted in responses in some patients with advanced renal cell carcinoma (RCC). However, the relative therapeutic benefit of the addition of LAK to IL‐2 was unknown. Methods. A randomized Phase III trial was conducted in patients with RCC comparing continuous intravenous infusion (CI) IL‐2 alone with CI IL‐2 plus LAK. Interleukin‐2 was administered at 3 × 106 U/m2/day on days 1–5, 13–17, 21–24, and 28–31. Patients on the LAK treatment arm underwent leukapheresis on days 8–10 and LAK cell reinfusion on days 13–15. The results are reported with long‐term follow‐up. The published experience with IL‐2 alone or with the addition of LAK was investigated in a quantitative literature survey. The response proportions were studied by schedule (high dose bolus, moderate dose, low dose) and by concomitant administration of LAK. Results. Seventy‐one patients were treated, 36 on the IL‐2 arm and 35 on the IL‐2 plus LAK arm. Four patients (6%) had major responses (two complete, two partial). The median survival of all patients was 13 months (95% confidence interval [CI], 9–18 months). There were no differences between treatment arms with regard to response (P=0.61) and survival (P=0.67). More patients on the LAK arm experienced pulmonary toxicity (P=0.008). The overall weighted response proportion was 16% (95% CI, 8%‐24%) for the 39 published series of 1291 patients treated with IL‐2. The 95% confidence intervals for response proportion overlapped when compared by schedule and by administration of LAK. Conclusions. The dose and schedule of IL‐2 used in this study resulted in a low level of antitumor activity and the addition of LAK did not improve the response rate against RCC. Given the infrequent, but reproducible, responses with IL‐2 and interferon‐based regimens, continued investigation of these agents is warranted as is the study of new cytokines. Alternative treatment strategies should be studied in RCC and new agents and treatment regimens that appear promising in Phase II studies must be studied in randomized tria.

PURPOSE A phase II trial of interferon alfa-2a (IFN) and 13-cis-retinoic acid (CRA) was conducted in patients with renal cell carcinoma (RCC). In vitro studies were performed to investigate potential mechanisms of interaction. PATIENTS AND METHODS Forty-four patients were treated. IFN was given daily at 3 MU and escalated to 6 and 9 MU if tolerated. The dose of CRA was 1 mg/kg/d. The effects of combining CRA and IFN on the proliferation of five RCC cell lines were examined, and retinoid sensitivity was correlated to the expression of retinoic acid receptors. RESULTS Thirteen (30%) of 43 assessable patients achieved a major response (three complete and 10 partial). Responding sites included bone metastases and renal primary tumors. Seven responding patients remain progression-free at 10+ to 19+ months. The response proportion was higher than in our prior experience with IFN, which was 10% in 149 patients. Eleven of 12 renal cancer cell lines were resistant to CRA alone; one, SK-RC-06, showed 90% inhibition of cell growth. CRA augmented the antiproliferative effect of IFN in several IFN-sensitive cell lines, but not in IFN-resistant lines. Northern blot analysis showed that expression of retinoic acid receptor-beta (RAR-beta) was repressed and not induced by retinoic acid in retinoic acid-insensitive RCC lines. However, RAR-beta expression was induced by retinoic acid in SK-RC-06 cells. CONCLUSION IFN and CRA showed antitumor activity in patients with advanced RCC, and the proportion and nature of response suggested CRA added therapeutic benefit to IFN. A phase III randomized trial of IFN plus CRA versus IFN alone and a phase II trial of single-agent CRA have been initiated.

Combined provision and discussion of SCPs help survivors construct a useful understanding of their cancer experience and may promote long-term self-management.

Fifteen patients with advanced renal cell carcinoma were treated on a phase II trial with topotecan. None of the fourteen evaluable patients achieved a complete or partial response. Myelosuppression was the most common toxicity. Eighty percent (12 of 15) of patients experienced grade III or IV neutropenia and/or anemia. Topotecan is not efficacious in the treatment of advanced renal cell carcinoma.

The aim of this study was to determine the antitumor activity of 13-cis-retinoic acid as a single agent in patients with advanced renal cell carcinoma. Eligible patients had advanced renal cell carcinoma with bi-dimensionally measurable disease, a Karnofsky performance status of at least 70, life expectancy of greater than three months, no evidence of brain metastases, and treatment with no more than one chemotherapy regimen. Patients were treated with one mg/kg/day of 13-cis-retinoic acid orally. Twenty-six patients were enrolled in this study and 25 were evaluable for response and toxicity. Of the twenty-five evaluable patients, no major responses were achieved. Toxicity was mild, with no patient requiring a dose reduction. At the dose administered in this trial, 13-cis-retinoic acid is inactive as a single agent in renal cell carcinoma.