A Phase II trial of intravenous gemcitabine and 5‐fluorouracil with subcutaneous interleukin‐2 and interferon‐α in patients with metastatic renal cell carcinoma

Abstract

BACKGROUND The objective of this study was to determine the response rate and toxicity of gemcitabine and continuous‐infusion 5‐fluorouracil (5‐FU) in combination with subcutaneous interleukin‐2 (IL2) and interferon‐α (IFNA) in patients with metastatic renal cell carcinoma. METHODS Forty‐one patients were treated with gemcitabine 600 mg/m2 on Days 1, 8, and 15 and continuous‐infusion 5‐FU on Days 1–21. The dose of 5‐FU was 200 mg/m2 per day for the initial 8 patients but was reduced to 150 mg/m2 per day for all remaining patients due to toxicity. Starting on Day 15, IL2 and IFNA were administered for 4 weeks. IL2 was administered at a dose of 11 × 106 IU subcutaneously (sc) 4 days per week and IFNA was administered at a dose of 10.0 × 106 IU sc 2 days per week. RESULTS Of 41 patients enrolled in the study, there was 1 complete response (CR), and there were 5 partial responses (PR), for an overall response rate of 14.6% (90% confidence interval [90%CI], 6.6–26.9%). The median time to disease progression was 6.6 months (90%CI, 3.9–7.5 months), and the median overall survival was 20.6 months (90%CI, 9.6–23.3 months). Toxicity was moderate to severe, with fatigue, fever, anorexia, or nausea experienced by 75–90% of patients. Mucositis and neutropenia, likely due to the gemcitabine and 5‐FU, were experienced by a majority of patients. CONCLUSIONS The addition of gemcitabine and 5‐FU to subcutaneous IL2 and IFNA results in a similar response rate to what was observed in previous studies of IL2‐based therapy. The toxicity of this four‐drug combination is significant, and the regimen is not recommended for further development. Cancer 2002;94:2602–9. © 2002 American Cancer Society. DOI 10.1002/cncr.10528

A randomized phase II trial of interleukin-2 in combination with four different doses of bryostatin-1 in patients with renal cell carcinoma

“…Bryostatin-1 has been shown in pre-clinical studies to augment certain immune responses particularly when combined with IL-2. The dose of IL-2 used in this study is the standard regimen used at our institution and is similar to doses used in other studies where responses were observed [26][27][28][29]. Bryostatin-1 had undergone Phase I evaluation on several schedules and the recommended doses for phase II studies was 25-35 mcg/m 2 /week as a single agent.…”

Gemcitabine and oxaliplatin in the treatment of patients with immunotherapy‐resistant advanced renal cell carcinoma

“…25 Recently, the combination of gemcitabine and 5-FU proved to be active against RCC, 14 but no further improvements were recorded when either cisplatin, 19 interferon, or IL-2 18 was added; furthermore, a Phase II study of gemcitabine, 5-FU, and oral thalidomide resulted in an unacceptably high incidence of thromboembolic complications. 20 In the current Phase II study, we tested the combination of gemcitabine with L-OHP in a population of chemotherapy-naïve patients with RCC who experienced disease progression after first-line immunotherapy.…”

“…However, our findings are in agreement with results reported by a group at the University of Chicago; in 2 distinct Phase II studies, those investigators tested the antitumor activity of gemcitabine combined with continuous-infusion 5-FU alone or with continuous-infusion 5-FU plus immunotherapy (IL-2 and interferon-␣) and found overall response rates of 17% and 14.6%, respectively. 14,18 At least two other gemcitabine-based Phase II studies have reported higher response rates (31% in a single-agent feasibility study 15 and 28% for the combination of gemcitabine, IL-2, and interferon-␣. 17 ) than the one noted in the current study.…”

“…10 More recently, it has been shown that gemcitabine-containing combinations also exert some antitumor activity in patients with immunotherapy-resistant advanced RCC. [11][12][13][14][15][16][17][18][19][20] Herein, we report the results of a single-institution Phase II study in which we evaluated the antitumor activity and toxicity of a combination of gemcitabine with the platinum derivative oxaliplatin (L-OHP).…”

New treatment approaches for metastatic renal cell carcinoma

“…The regimen was generally well tolerated. Expanding on this approach, the same researchers performed a phase II trial of gemcitabine and 5-FU in combination with IL-2 and IFN-␣ [21]. Although only 16 patients were entered, there were three partial responses and an additional fourth patient with stable disease.…”