Combination of sorafenib and doxorubicin in patients with advanced hepatocellular carcinoma: results from a phase I extension trial.
Sorafenib, an oral multikinase inhibitor, shows efficacy in renal cell and hepatocellular carcinoma (HCC) and is well tolerated when combined with doxorubicin in other solid tumours. Eighteen patients with inoperable HCC received doxorubicin 60 mg/m(2) IV for up to six 3-week cycles. Sorafenib 400mg bid was administered continuously starting day 4. Patients discontinuing doxorubicin were eligible for sorafenib monotherapy. The most frequent grade 3-4 drug-related adverse events were neutropaenia (61%), leukopaenia (45%) and diarrhoea (17%, grade 3). Seven of eight patients who completed six cycles of doxorubicin continued treatment with sorafenib for at least 3 months. Doxorubicin moderately increased AUC (21%) and C(max) (33%) when administered with sorafenib. The disease control rate for 16 evaluable patients was 69%. Sorafenib plus doxorubicin appears to be well tolerated and more effective in the treatment of HCC than doxorubicin alone. Follow-up with single-agent sorafenib in these patients also appears to be well tolerated.
Richly
H
H
Department of Medical Oncology and Cancer Research, University of Essen, Hufelandstrasse 55, 45122 Essen, Germany. heike.richly@uni-due.de
Schultheis
B
B
Adamietz
I A
IA
Kupsch
P
P
Grubert
M
M
Hilger
R A
RA
Ludwig
M
M
Brendel
E
E
Christensen
O
O
Strumberg
D
D
D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects* / Q000097:blood / Q000627:therapeutic use; D001557:Benzenesulfonates / Q000008:administration & dosage / Q000009:adverse effects / Q000097:blood; D006528:Carcinoma, Hepatocellular / Q000097:blood / Q000188:drug therapy*; D004317:Doxorubicin / Q000008:administration & dosage / Q000009:adverse effects / Q000097:blood; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D008113:Liver Neoplasms / Q000097:blood / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D009536:Niacinamide / Q000031:analogs & derivatives; D010671:Phenylurea Compounds; D011725:Pyridines / Q000008:administration & dosage / Q000009:adverse effects / Q000097:blood; D000077157:Sorafenib; D016896:Treatment Outcome
D001557:Benzenesulfonates; D010671:Phenylurea Compounds; D011725:Pyridines; D009536:Niacinamide; D004317:Doxorubicin; D000077157:Sorafenib