Initial clinical response predicts outcome and is associated with dose schedule in metastatic melanoma and renal cell carcinoma patients treated with high-dose interleukin 2.
High-dose interleukin (IL)-2 is an effective agent for the treatment of metastatic malignant melanoma and renal cell carcinoma. This study evaluated the outcomes of patients receiving two commonly used intravenous IL-2 schedules that have never been directly compared.



Forty-seven metastatic malignant melanoma and renal cell carcinoma patients were identified from a prospective database who underwent high-dose IL-2 therapy (720,000 or 600,000 IU/kg) during 1999 to 2003. Disease-specific survival (DSS) was calculated by the Kaplan-Meier method with the log-rank test on an intention-to-treat basis. Multivariate Cox regression analysis of prognostic variables associated with outcome was performed. Factors associated with initial response and prevention of disease progression were determined.



Objective response (5 partial and 5 mixed) or disease stabilization was noted in 9 (20%) and 10 (22%), respectively, of 46 assessable patients after 1 course of therapy. Four patients (22%) achieved disease-free status after the third course of IL-2 (n = 1) or surgical resection of confined metastatic disease (n = 3). At 19.1 months' median follow-up, factors associated with improved DSS included an initial clinical response to IL-2 therapy (P < .001) and a higher administered dose (P = .04). Patients who received 720,000 IU/kg were more likely to experience an initial major objective response (P = .03) and disease stabilization (P = 0.03) independent of the tumor treated. Objective response early in the course of therapy was the only independent predictor of tumor-related mortality (P = .004).



The initial clinical response to IL-2 therapy is an independent predictor of improved outcome associated with DSS and the 720,000 IU/kg dose. These results support further prospective trials with increased IL-2 dose schedules in a larger cohort of patients.
Spanknebel
Kathryn
K
Department of Surgery, Columbia University College of Physicians and Surgeons, 177 Fort Washington Avenue, MHB-7SK 20, New York, New York, 10032, USA. ks2166@columbia.edu
Cheung
Kenneth Y
KY
Stoutenburg
John
J
Hurst-Wicker
Karl
K
Hesdorffer
Charles
C
Deraffele
Gail
G
Kaufman
Howard L
HL
D000293:Adolescent; D000328:Adult; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D002292:Carcinoma, Renal Cell / Q000401:mortality* / Q000628:therapy*; D005260:Female; D006801:Humans; D007167:Immunotherapy / Q000379:methods*; D007376:Interleukin-2 / Q000008:administration & dosage* / Q000009:adverse effects; D007680:Kidney Neoplasms / Q000401:mortality* / Q000628:therapy*; D008297:Male; D008545:Melanoma / Q000401:mortality* / Q000473:pathology / Q000628:therapy*; D008875:Middle Aged; D016019:Survival Analysis
D000970:Antineoplastic Agents; D007376:Interleukin-2