Phase I/II trial of subcutaneous interleukin-2, granulocyte-macrophage colony-stimulating factor and interferon-α in patients with metastatic renal cell carcinoma.

Abstract

OBJECTIVE:

To determine, in a phase I/II trial, the maximum tolerated dose (MTD), clinical activity and safety of concurrent subcutaneous (s.c.) interleukin-2 (IL-2), interferon-α2b (IFN-α) and granulocyte-macrophage colony-stimulating factor (GM-CSF).

PATIENTS AND METHODS:

Patients with metastatic renal cell carcinoma (RCC) received on a 3+3 trial design escalating doses of s.c. GM-CSF, IL-2 and IFN-α. Dose-limiting toxicities (DLTs) during the first 6-week cycle were used to determine the MTD. A phase II trial was then initiated to determine clinical activity.

RESULTS:

A total of sixty patients were enrolled in the study (phase I = 31; phase II = 29). Two DLTs were observed (G3 nausea/vomiting and fatigue) and the MTD was determined to be GM-CSF 5.0 µg/kg/day, IL-2 9.0 mIU/m(2)/day and IFN-α 5.0 mU/m(2)/day. Patients received a median (range) of four (one to 11) cycles of therapy. G3 adverse events were reported in 10 of 31 (32%) patients. The overall response rate was 20% (one complete response and 11 partial responses), including patients who were rendered free of disease with surgery. The median progression-free survival and overall survival were 6.0 and 23.4 months, respectively.

CONCLUSIONS:

Immunotherapy with concurrent s.c. GM-CSF, IL-2 and IFN-α is generally well tolerated. The overall response rate observed with this combination continues to show the efficacy of immunotherapy in a selected group of metastatic RCC patients.

• Authors: Jorge A Garcia, Tarek Mekhail, Paul Elson, Laura Wood, Ronald M Bukowski, Robert Dreicer, Brian I Rini
• Journal: BJU international (BJU Int) Vol. 109 Issue 1 Pg. 63-9 (Jan 2012) ISSN: 1464-410X [Electronic] England
• PMID: 21244601 (Publication Type: Clinical Trial, Phase I, Clinical Trial, Phase II, Comparative Study, Journal Article, Multicenter Study, Randomized Controlled Trial)
• Copyright: © 2010 THE AUTHORS. BJU INTERNATIONAL © 2010 BJU INTERNATIONAL.

Chemical References

• Immunologic Factors
• Interferon-alpha
• Interleukin-2
• Granulocyte-Macrophage Colony-Stimulating Factor

Topics

• Adult
• Aged
• Carcinoma, Renal Cell (diagnosis, drug therapy, secondary)
• Disease-Free Survival
• Dose-Response Relationship, Drug
• Drug Therapy, Combination
• Female
• Granulocyte-Macrophage Colony-Stimulating Factor (administration & dosage)
• Humans
• Immunologic Factors (administration & dosage)
• Injections, Subcutaneous
• Interferon-alpha (administration & dosage)
• Interleukin-2 (administration & dosage)
• Kidney Neoplasms (drug therapy, mortality, pathology)
• Male
• Middle Aged
• Neoplasm Metastasis
• Survival Rate (trends)
• Treatment Outcome
• United States (epidemiology)