Phase I trial of sorafenib in combination with interferon-alpha in Japanese patients with unresectable or metastatic renal cell carcinoma.
BACKGROUND
We investigated the safety, pharmacokinetics, tumor response, and immunological parameters of sorafenib plus interferon α-2b [corrected] (IFN) in Japanese patients with advanced RCC.


METHODS
After 2 weeks of IFN-alone treatment, eligible patients received 28-day cycles of continuous sorafenib 200 mg (Cohort 1) or 400 mg (Cohorts 2 and 3) twice daily combined with intramuscular IFN 6 (Cohorts 1 and 2) or 9 (Cohort 3) million international units (MIU) three times a week.


RESULTS
A total of 18 patients received at least one dose of sorafenib plus IFN. Five patients had dose-limiting toxicities (DLTs). The most common DLT was fatigue, experienced in four DLT patients. All 18 patients experienced at least one treatment-emergent adverse event (AE). The most common treatment-emergent AEs included fatigue, fever, platelets, leukocytes, hemoglobin, weight loss and anorexia. Five patients had confirmed partial response and 11 had stable disease, a response rate of 27.8%. IFN had no relevant impact on the pharmacokinetics of sorafenib.


CONCLUSIONS
Sorafenib administered in combination with IFN was well tolerated, with promising results in efficacy. Continuous sorafenib 400 mg twice daily in combination with IFN 6 MIU three times a week is recommended in Japanese patients with advanced RCC.
Division of Urology, Shizuoka Cancer Center Hospital, 1007 Shimonagakubo, Nagaizumi, Shizuoka, 411-8777, Japan. m.niwakawa@scchr.jp
Masashi
M
Niwakawa
Katsuyoshi
K
Hashine
Raizo
R
Yamaguchi
Hirofumi
H
Fujii
Yasuo
Y
Hamamoto
Koichi
K
Fukino
Takahiko
T
Tanigawa
Yoshiteru
Y
Sumiyoshi
D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000493:pharmacokinetics; D044466:Asian People; D001557:Benzenesulfonates / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics; D002292:Carcinoma, Renal Cell / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D005260:Female; D006801:Humans; D007155:Immunologic Factors / Q000008:administration & dosage; D016898:Interferon-alpha / Q000008:administration & dosage; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009536:Niacinamide / Q000031:analogs & derivatives; D010671:Phenylurea Compounds; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics; D011725:Pyridines / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics; D000077157:Sorafenib; D047368:Tumor Burden / Q000187:drug effects
D000970:Antineoplastic Agents; D001557:Benzenesulfonates; C554163:IFNA6 protein, human; D007155:Immunologic Factors; D016898:Interferon-alpha; D010671:Phenylurea Compounds; D047428:Protein Kinase Inhibitors; D011725:Pyridines; D009536:Niacinamide; D000077157:Sorafenib
N Engl J Med. 2008 Jul 24;359(4):378-90
18650514
Ann Clin Lab Sci. 1997 Nov-Dec;27(6):391-5
9433535
Cancer Sci. 2008 Jan;99(1):159-65
17953709
Biomed Res. 2008 Dec;29(6):271-8
19129670
Cancer J. 2008 Sep-Oct;14(5):320-4
18836337
N Engl J Med. 1996 Sep 19;335(12):865-75
8778606
Cancer Sci. 2008 Jul;99(7):1492-8
18477034
J Clin Oncol. 2009 Mar 10;27(8):1280-9
19171708
Jpn J Clin Oncol. 2007 Oct;37(10):755-62
17951335
N Engl J Med. 2007 Jan 11;356(2):125-34
17215530
Clin Cancer Res. 2007 Mar 15;13(6):1801-9
17363536
J Natl Cancer Inst. 2000 Feb 2;92(3):205-16
10655437