Subcutaneous interleukin-2 and interferon alpha in the treatment of patients with metastatic renal cell carcinoma-Less efficacy compared with intravenous interleukin-2 and interferon alpha. Results of a multicenter Phase II trial from the Groupe Français d'Immunothérapie

Cancer. 2002 Dec 1;95(11):2324-30. doi: 10.1002/cncr.10968.

Abstract

Background: The main objective of this trial was to evaluate the combination of subcutaneous (SC) interleukin-2 (IL-2) with interferon alpha-2a (IFN-alpha) in the treatment of patients with metastatic renal cell carcinoma (MRCC) compared with a previous trial that used continuous-infusion IL-2 and IFN-alpha with identical schedules and dosages.

Methods: Between April, 1997 and January, 1998, 66 patients with MRCC received SC IL-2 at a dose of 9 x 10(6) IU/m(2) twice daily for 5 days during 2 induction cycles and during 4 additional cycles, with a 3-week rest between cycles. Each induction cycle consisted of two 5-day courses of IL-2 separated by a 9-day break. IFN-alpha at a dose of 6 x 10(6) IU per day three times per week was given during induction cycles and additional cycles.

Results: All patients were assessable for response and toxicity. The median follow-up was 43 months. Thirty-five patients (51%) and 43 patients (63%) received >or= 80% of the planned induction doses of IL-2 and IFN-alpha, respectively. Five patients achieved objective responses (7.6%; 95% confidence interval [95%CI], 2.5-16.8%), with two complete responses. The median survival was 14 months (95%CI, 11.3-16.7 months). Fifty-three patients (80%) had at least one episode of Grade 3 toxicity related to treatment. Twenty-two patients developed Grade 4 toxicities, which included hypotension (24% of patients), decreased performance status (6% of patients), dyspnea (3% of patients), and mucositis (3% patients) as well as fever, ventricular tachycardia, and anemia.

Conclusions: The current results seem to indicate reduced efficacy and higher toxicity rates with SC IL-2 plus IFN-alpha compared with the results from a previous trial that used an identical regimen with IV IL-2 administration. Although SC IL-2 regimens are used widely, their interest remains to be determined.

Publication types

  • Clinical Trial
  • Clinical Trial, Phase II
  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Agents / administration & dosage*
  • Antineoplastic Agents / adverse effects
  • Antineoplastic Agents / pharmacology*
  • Carcinoma, Renal Cell / drug therapy*
  • Carcinoma, Renal Cell / pathology
  • Female
  • Health Status
  • Humans
  • Hypotension / chemically induced
  • Injections, Intravenous
  • Injections, Subcutaneous
  • Interferon-alpha / administration & dosage*
  • Interferon-alpha / adverse effects
  • Interferon-alpha / pharmacology*
  • Interleukin-2 / administration & dosage*
  • Interleukin-2 / adverse effects
  • Interleukin-2 / pharmacology*
  • Kidney Neoplasms / drug therapy*
  • Kidney Neoplasms / pathology
  • Male
  • Middle Aged
  • Survival Analysis
  • Treatment Outcome

Substances

  • Antineoplastic Agents
  • Interferon-alpha
  • Interleukin-2