title: Efficacy and safety of inhaled recombinant interleukin-2 in high-risk renal cell cancer patients compared with systemic interleukin-2: an outcome study.
abstract: 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. Ninety-four 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 IFNalpha. 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.
authors.affiliation: Department of Urology, University Hospital Hamburg-Eppendorf, Germany. Huland@uke.uni-hamburg.de
authors.forename: E
authors.initials: E
authors.lastname: Huland
authors.forename: A
authors.initials: A
authors.lastname: Burger
authors.forename: J
authors.initials: J
authors.lastname: Fleischer
authors.forename: P
authors.initials: P
authors.lastname: Fornara
authors.forename: E
authors.initials: E
authors.lastname: Hatzmann
authors.forename: A
authors.initials: A
authors.lastname: Heidenreich
authors.forename: H
authors.initials: H
authors.lastname: Heinzer
authors.forename: H
authors.initials: H
authors.lastname: Heynemann
authors.forename: L
authors.initials: L
authors.lastname: Hoffmann
authors.forename: R
authors.initials: R
authors.lastname: Hofmann
authors.forename: H
authors.initials: H
authors.lastname: Huland
authors.forename: I
authors.initials: I
authors.lastname: Kämpfer
authors.forename: M
authors.initials: M
authors.lastname: Kindler
authors.forename: H
authors.initials: H
authors.lastname: Kirchner
authors.forename: G
authors.initials: G
authors.lastname: Mehlhorn
authors.forename: T H
authors.initials: TH
authors.lastname: Moniak
authors.forename: U
authors.initials: U
authors.lastname: Rebmann
authors.forename: J
authors.initials: J
authors.lastname: Roigas
authors.forename: T H
authors.initials: TH
authors.lastname: Schneider
authors.forename: D
authors.initials: D
authors.lastname: Schnorr
authors.forename: H J
authors.initials: HJ
authors.lastname: Schmitz
authors.forename: R
authors.initials: R
authors.lastname: Wenisch
authors.forename: Z
authors.initials: Z
authors.lastname: Varga
authors.forename: J
authors.initials: J
authors.lastname: Vinke
mesh_terms: D000280:Administration, Inhalation; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D007279:Injections, Subcutaneous; D016898:Interferon-alpha / Q000008:administration & dosage / Q000627:therapeutic use; D007376:Interleukin-2 / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use*; D007680:Kidney Neoplasms / Q000188:drug therapy*; D008175:Lung Neoplasms / Q000188:drug therapy / Q000556:secondary; D008297:Male; D008875:Middle Aged; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use*; D015996:Survival Rate; D013997:Time Factors
chemical_list: D016898:Interferon-alpha; D007376:Interleukin-2; D011994:Recombinant Proteins