Gemcitabine plus sorafenib in patients with advanced pancreatic cancer: a phase II trial of the University of Chicago Phase II Consortium.
BACKGROUND
Sorafenib, an inhibitor of B-raf, VEGFR2, and PDGFR-β, has activity against pancreatic cancer in preclinical models. In a phase I trial of gemcitabine plus sorafenib, 57% of pancreatic cancer patients achieved stable disease.


METHODS
We conducted a multi-center phase II trial of sorafenib plus gemcitabine in chemo-naïve patients with histologically-confirmed, advanced pancreatic cancer. Patients received sorafenib 400 mg twice daily and gemcitabine 1,000 mg/m(2) on days 1, 8 and 15 of a 28 day cycle.


RESULTS
Seventeen patients enrolled at 4 centers; 13 were evaluable for response. There were no objective responses; 18% had stable disease. Median overall survival was 4.0 months (95% CI: 3.4, 5.9); median progression-free survival was 3.2 months (95% CI: 1.6, 3.6). Grade 3/4 toxicities included thrombosis in 18% of patients, dehydration or hand-foot syndrome in 12%, and hypertension or gastrointestinal bleeding in 6%.


CONCLUSIONS
Gemcitabine plus sorafenib is inactive in advanced pancreatic cancer.
Kindler
Hedy Lee
HL
Department of Medicine, Section of Hematology/Oncology, University of Chicago, 5841 South Maryland Avenue, MC 2115, Chicago, IL 60637, USA. hkindler@medicine.bsd.uchicago.edu
Wroblewski
Kristen
K
Wallace
James A
JA
Hall
Michael J
MJ
Locker
Gershon
G
Nattam
Sreenivasa
S
Agamah
Edem
E
Stadler
Walter M
WM
Vokes
Everett E
EE
D000230:Adenocarcinoma / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D001557:Benzenesulfonates / Q000008:administration & dosage; D002641:Chicago; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D018572:Disease-Free Survival; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009536:Niacinamide / Q000031:analogs & derivatives; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D010671:Phenylurea Compounds; D011725:Pyridines / Q000008:administration & dosage; D000077157:Sorafenib; D013997:Time Factors; D016896:Treatment Outcome; D014495:Universities; D000093542:Gemcitabine
D001557:Benzenesulfonates; D010671:Phenylurea Compounds; D011725:Pyridines; D003841:Deoxycytidine; D009536:Niacinamide; D000077157:Sorafenib; D000093542:Gemcitabine
Control Clin Trials. 1989 Mar;10(1):1-10
2702835
CA Cancer J Clin. 2009 Jul-Aug;59(4):225-49
19474385
J Clin Oncol. 2007 May 20;25(15):1960-6
17452677
Science. 2003 Jul 4;301(5629):94-6
12843393
Cancer Res. 2007 Mar 1;67(5):2098-106
17332339
J Clin Oncol. 1997 Jun;15(6):2403-13
9196156
Cancer Res. 2004 Oct 1;64(19):7099-109
15466206
Lancet. 2008 Jun 21;371(9630):2101-8
18514303
Mol Cancer Ther. 2008 Oct;7(10):3129-40
18852116
J Clin Oncol. 2010 Aug 1;28(22):3617-22
20606091
Clin Cancer Res. 2006 Jan 1;12(1):144-51
16397036
Curr Oncol Rep. 2007 May;9(3):170-6
17430687
Mol Cancer Ther. 2008 Nov;7(11):3509-18
19001434
Hepatobiliary Pancreat Dis Int. 2008 Aug;7(4):345-56
18693168
Lancet Oncol. 2004 Nov;5(11):655-63
15522652
Am J Hematol. 2008 Nov;83(11):862-70
18819092
J Natl Cancer Inst. 2000 Feb 2;92(3):205-16
10655437
J Clin Oncol. 2005 Nov 1;23(31):8033-40
16258101
J Clin Oncol. 2009 Aug 10;27(23):3778-85
19581537
J Clin Oncol. 2009 May 1;27(13):2231-7
19307500