title: 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.
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.
authors.affiliation: Department of Medicine, Institut Bergonié, Bordeaux, France.
authors.forename: Alain
authors.initials: A
authors.lastname: Ravaud
authors.forename: Rémy
authors.initials: R
authors.lastname: Delva
authors.forename: Fréderic
authors.initials: F
authors.lastname: Gomez
authors.forename: Christine
authors.initials: C
authors.lastname: Chevreau
authors.forename: Jean-Yves
authors.initials: JY
authors.lastname: Douillard
authors.forename: Jean
authors.initials: J
authors.lastname: Peny
authors.forename: Bruno
authors.initials: B
authors.lastname: Coudert
authors.forename: Sylvie
authors.initials: S
authors.lastname: Négrier
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000494:pharmacology*; D002292:Carcinoma, Renal Cell / Q000188:drug therapy* / Q000473:pathology; D005260:Female; D006304:Health Status; D006801:Humans; D007022:Hypotension / Q000139:chemically induced; D007275:Injections, Intravenous; D007279:Injections, Subcutaneous; D016898:Interferon-alpha / Q000008:administration & dosage* / Q000009:adverse effects / Q000494:pharmacology*; D007376:Interleukin-2 / Q000008:administration & dosage* / Q000009:adverse effects / Q000494:pharmacology*; D007680:Kidney Neoplasms / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D016898:Interferon-alpha; D007376:Interleukin-2