Phase II trial of sorafenib plus interferon alfa-2b as first- or second-line therapy in patients with metastatic renal cell cancer.
OBJECTIVE
We undertook this study to determine the activity and tolerability of sorafenib administered with interferon alfa-2b (IFN-alpha-2b) as first- or second-line therapy in metastatic renal cell cancer (RCC).


METHODS
Between November 2004 and October 2006, 40 patients at two sites were enrolled onto a phase II trial of sorafenib plus IFN-alpha-2b. Treatment consisted of 8-week cycles of sorafenib 400 mg orally bid plus IFN-alpha-2b 10 million U subcutaneously three times a week followed by a 2-week break. Patients were eligible to receive additional cycles of therapy until disease progression. Dose reduction of both drugs by 50% was permitted once for toxicity.


RESULTS
The response rate was 33% (95% CI, 19% to 49%; 13 of 40 patients), including 28% partial responses (n = 11) and 5% complete responses (n = 2). Responses were seen in treatment-naïve and interleukin-2 (IL-2) -treated patients within the first two cycles. The median duration of response was 12 months. With a median follow-up time of 14 months, median progression-free survival time was 10 months (95% CI, 8 to 18 months), and median overall survival time has not yet been reached. Fatigue, anorexia, anemia, diarrhea, hypophosphatemia, rash, nausea, and weight loss were the most common toxicities. Grade 3 toxicities were uncommon but included hypophosphatemia, neutropenia, rash, fatigue, and anemia. Dose reductions were required in 65% of patients.


CONCLUSIONS
The combination of sorafenib and IFN-alpha-2b has substantial activity in treatment-naïve and IL-2-treated patients with RCC. The toxicity exceeded that of either drug alone, but dose reductions and breaks between cycles allowed for chronic therapy. A larger, randomized trial would determine whether there is any advantage to this regimen compared with sorafenib alone.
Division of Medical Oncology, Department of Medicine, Duke University Medical Center, Durham, NC 27710, USA. jared.gollob@duke.edu
Jared A
JA
Gollob
W Kimryn
WK
Rathmell
Tina M
TM
Richmond
Christine B
CB
Marino
Elizabeth K
EK
Miller
Gayle
G
Grigson
Catharine
C
Watkins
Lin
L
Gu
Bercedis L
BL
Peterson
John J
JJ
Wright
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D001557:Benzenesulfonates / Q000008:administration & dosage* / Q000009:adverse effects; D002292:Carcinoma, Renal Cell / Q000188:drug therapy* / Q000556:secondary*; D005260:Female; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000008:administration & dosage* / Q000009:adverse effects; D007680:Kidney Neoplasms / Q000188:drug therapy* / Q000473:pathology; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009536:Niacinamide / Q000031:analogs & derivatives; D009657:North Carolina; D010671:Phenylurea Compounds; D011725:Pyridines / Q000008:administration & dosage* / Q000009:adverse effects; D011994:Recombinant Proteins; D000077157:Sorafenib; D014057:Tomography, X-Ray Computed; D016896:Treatment Outcome
D001557:Benzenesulfonates; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D010671:Phenylurea Compounds; D011725:Pyridines; D011994:Recombinant Proteins; D009536:Niacinamide; D000077157:Sorafenib