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.
Gollob
Jared A
JA
Division of Medical Oncology, Department of Medicine, Duke University Medical Center, Durham, NC 27710, USA. jared.gollob@duke.edu
Rathmell
W Kimryn
WK
Richmond
Tina M
TM
Marino
Christine B
CB
Miller
Elizabeth K
EK
Grigson
Gayle
G
Watkins
Catharine
C
Gu
Lin
L
Peterson
Bercedis L
BL
Wright
John J
JJ
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