Cytokines in Patients With Metastatic Renal Cell Carcinoma of Intermediate Prognosis

The PERCY Quattro trial has been designed to evaluate the survival benefit of two cytokine treatments, Interleukin-2 (IL2) and/or alpha interferon (IFN), for patients with intermediate chance of response in metastatic renal cell carcinoma. Eligible patients will be randomly assigned in a two-by-two factorial design to either medroxyprogesterone (MPA), subcutaneous IFN, subcutaneous IL2, or a combination of IFN and IL2. The primary objective of the study is overall survival; secondary objectives are progression-free survival, response rate, toxicity, and quality of life.

Sex

All

Minimum age

18 Years

Inclusion Criteria:

* Progressive histologically proven metastatic renal cell carcinoma.
* Patient with only 1 metastatic site and Karnofsky = 80% or more than 1 metastatic site and Karnofsky \>= 80%.
* Age \>= 18
* No wide-field radiation therapy for 6 weeks at least.
* No active brain metastasis.
* Blood values within limits of normal (hematocrit \> 30% and leukocyte count \>= 4x109/l and platelet count \>= 120x109/l).
* Creatinine \< 150 µmol/l and bilirubin \<= normal.
* Female patients of childbearing potential: effective method of contraception is necessary.
* Written, voluntary, informed consent.

Exclusion Criteria:

* Previous treatment with cytokines.
* Only one metastatic organ and Karnofsky = 90% or 100% (inclusion in good prognosis group).
* More than one metastatic organ (at least one metastasis to the liver) and \<12 months between initial diagnosis and diagnosis of metastasis.
* Active brain metastases.
* Patient with concurrent grade III/IV heart disorder (congestive heart failure, coronary artery disease, uncontrolled hypertension, severe arrhythmia, etc) and/or stroke volume \< 50%.
* Severe pulmonary, hepatic, or renal disease potentially aggravated by treatment.
* Severe concurrent infection necessitating antibiotics
* Patient with known HIV or AIDS-related disease, or presence of HB antigen or known chronic hepatitis.
* Previous allograft.
* Patient under corticosteroid treatment.
* Previous or concurrent primary malignancies at other sites (except from baso-cellular skin cancer or cervical cancer in situ)
* Pregnant or lactating woman.
* Follow-up difficult because of geography or personal circumstances.

• BACKGROUNDNegrier S, Escudier B, Lasset C, Douillard JY, Savary J, Chevreau C, Ravaud A, Mercatello A, Peny J, Mousseau M, Philip T, Tursz T. Recombinant human interleukin-2, recombinant human interferon alfa-2a, or both in metastatic renal-cell carcinoma. Groupe Francais d'Immunotherapie. N Engl J Med. 1998 Apr 30;338(18):1272-8. doi: 10.1056/NEJM199804303381805. PMID 9562581
• BACKGROUNDRavaud A, Delva R, Gomez F, Chevreau C, Douillard JY, Peny J, Coudert B, Negrier S; Groupe Francais d'Immunotherapie. 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 Francais d'Immunotherapie. Cancer. 2002 Dec 1;95(11):2324-30. doi: 10.1002/cncr.10968. PMID 12436438
• BACKGROUNDNegrier S, Escudier B, Gomez F, Douillard JY, Ravaud A, Chevreau C, Buclon M, Perol D, Lasset C. Prognostic factors of survival and rapid progression in 782 patients with metastatic renal carcinomas treated by cytokines: a report from the Groupe Francais d'Immunotherapie. Ann Oncol. 2002 Sep;13(9):1460-8. doi: 10.1093/annonc/mdf257. PMID 12196373