First-line bevacizumab combined with reduced dose interferon-alpha2a is active in patients with metastatic renal cell carcinoma.
BACKGROUND
In patients with untreated metastatic renal cell carcinoma (mRCC), progression-free survival (PFS) was longer with bevacizumab + interferon (IFN)-alpha than IFN + placebo (AVOREN trial). In this hypothesis-generating study, subgroup analysis was carried out to determine the effect of IFN dose reduction.


METHODS
A total of 649 patients received IFN 9 MIU s.c. three times weekly plus bevacizumab 10 mg/kg or placebo every 2 weeks until disease progression. The IFN dose was reduced to 6 or 3 MIU with the development of IFN-attributed toxicity. Differences between treatment arms in PFS, response rate and tolerability were analysed in the reduced-dose group.


RESULTS
IFN dose was reduced in 131 patients in the bevacizumab + IFN arm and 97 patients in the IFN + placebo arm during the trial. PFS rates in the bevacizumab + reduced-dose IFN group were comparable with the total population (Kaplan-Meier estimates of event-free rate at 1 year: 0.524 versus 0.427). Bevacizumab + reduced-dose IFN was well tolerated, with substantial decreases in the rate of adverse events following dose reduction.


CONCLUSIONS
This retrospective subgroup analysis suggests that the dose of IFN can be reduced to manage side-effects while maintaining efficacy in patients with mRCC receiving bevacizumab + IFN.
Melichar
B
B
Charles University Medical School and Teaching Hospital, Hradec Králové, Czech Republic. Electronic address: melichar@fnhk.cz.
Koralewski
P
P
Szpital im. Rydygiera, Krakow, Poland.
Ravaud
A
A
Department of Medical Oncology and Radiotherapy, Hôpital Saint André, CHU Bordeaux, Bordeaux, France.
Pluzanska
A
A
Klinika Chemioterapii AM, Lodz, Poland.
Bracarda
S
S
Department of Medical Oncology, Azienda Ospedaliera, Perugia, Italy.
Szczylik
C
C
Oncology Clinic, Wojskowy Instytut Medyczny, Warsaw, Poland.
Chevreau
C
C
Department of Medical Oncology, Institut Claudius-Regaud, Toulouse Cedex, France.
Filipek
M
M
Szpital Wojewodzki im. Sw. Lukasz, Tarnow, Poland.
Delva
R
R
Department of Medical Oncology, Centre Paul Papin, Angers.
Sevin
E
E
Centre Régional François Baclesse de Lutte contre le Cancer, Caen.
Négrier
S
S
Department of Medical Oncology, Centre Léon Bérard, Lyon, France.
McKendrick
J
J
Department of Medical Oncology, Box Hill Hospital, Box Hill, Australia.
Santoro
A
A
Department of Oncology and Hematology, Istituto Clinico Humanitas, Rozzano, Italy.
Pisa
P
P
F. Hoffmann-La Roche Ltd, Basel, Switzerland.
Escudier
B
B
Department of Medicine, Institut Gustave Roussy, Villejuif, France.
D020533:Angiogenesis Inhibitors / Q000008:administration & dosage; D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D061067:Antibodies, Monoclonal, Humanized; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D000068258:Bevacizumab; D002292:Carcinoma, Renal Cell / Q000188:drug therapy*; D018572:Disease-Free Survival; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000008:administration & dosage; D007680:Kidney Neoplasms / Q000188:drug therapy*; D009362:Neoplasm Metastasis; D011994:Recombinant Proteins; D012189:Retrospective Studies; D016896:Treatment Outcome
D020533:Angiogenesis Inhibitors; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins; D000068258:Bevacizumab