Efficacy and Safety of Inhaled Recombinant Interleukin-2 in High-Risk Renal Cell Cancer Patients Compared with Systemic Interleukin-2: an Outcome Study

Huland, Edith; Burger, A.; Fleischer, J.; Fornara, P.; Hatzmann, E.; Heidenreich, A.; Heinzer, H.; Heynemann, H.; Hoffmann, L.; Hofmann, R.; Huland, H.; Kämpfer, I.; Kindler, M.; Kirchner, H.; Mehlhorn, G.; Moniak, T. H.; Rebmann, U.; Roigas, J.; Schneider, T. H.; Schnorr, D.; Schmitz, H.-J.; Wenisch, R.; Varga, Z.; Vinke, J.

doi:10.14712/fb2003049050183

Fol. Biol. 2003, 49, 183-190

https://doi.org/10.14712/fb2003049050183

Efficacy and Safety of Inhaled Recombinant Interleukin-2 in High-Risk Renal Cell Cancer Patients Compared with Systemic Interleukin-2: an Outcome Study

Edith Huland¹, A. Burger², J. Fleischer³, P. Fornara⁴, E. Hatzmann⁵, A. Heidenreich⁶, H. Heinzer¹, H. Heynemann⁴, L. Hoffmann⁷, R. Hofmann⁶, H. Huland¹, I. Kämpfer⁷, M. Kindler², H. Kirchner⁸, G. Mehlhorn⁹, T. H. Moniak⁹, U. Rebmann⁹, J. Roigas¹⁰, T. H. Schneider⁴, D. Schnorr¹⁰, H.-J. Schmitz³, R. Wenisch³, Z. Varga⁶, J. Vinke⁵

¹Department of Urology, University Hospital Hamburg-Eppendorf, Germany
²Onkologische Schwerpunktpraxis, Berlin, Germany
³St. Carolus Krankenhaus, Görlitz, Germany
⁴Martin-Luther-Universität Halle-Wittenberg, Halle, Germany
⁵Chiron BV, Amsterdam
⁶Philipps-Universität Marburg, Marburg, Germany
⁷Waldklinikum GmbH, Gera, Germany
⁸Klinikum Siloah, Germany
⁹Diakonissenkrankenhaus, Dessau, Germany
¹⁰Department of Urology, Charite, Humboldt Universität Berlin, Germany

Received October 2003
Accepted October 2003

Systemic IL-2 is an effective treatment for low to intermediate risk mRCC patients, its efficacy is marginal in high-risk cases. Therefore, other treatment approaches are required for this population. Ninetyfour high-risk patients with RCC and pulmonary metastases were treated with inhaled plus concomitant low-dose subcutaneous rhIL-2. Clinical response, survival and safety were compared with those from IL-2 given systemically at the registered dose and schedule in 103 comparable historical controls. In the rhIL-2 INH group, treatment consisted of 6.5 MIU rhIL-2 nebulized 5x/day and 3.3 MIU rhIL-2 SC once daily. The rhIL-2 SYS group received treatment which consisted of intravenous infusion of 18.0 MIU/m²/day rhIL-2 or SC injection of 3.6-18.0 MIU rhIL-2. Some patients in both groups also received IFNα. Mean treatment durations were 43 weeks rhIL-2 INH and 15 weeks rhIL-2 SYS. Significantly longer overall survival and progression-free survival durations were observed in the rhIL-2 INH group. The probability of survival at 5 years was 21% for the rhIL-2 INH group. No patients survived 5 years in the rhIL-2 SYS group. A multivariate analysis of overall survival adjusting for differences in baseline characteristics between the two treatment groups resulted in a risk ratio of 0.43 (95% CI 0.30-0.63; P < 0.0001). The data suggested an association between the response (SD or better) and survival, especially in the rhIL-2 INH group. The inhalation regimen was well tolerated. This outcome study suggests that administration of rhIL-2 by inhalation is efficacious and safe in high-risk mRCC patients with pulmonary metastases, who have no other treatment option available.