A phase II trial of gemcitabine, capecitabine, and bevacizumab in metastatic renal carcinoma.
OBJECTIVE
Renal cancer is resistant to most DNA and DNA repair targeted chemotherapy; although moderate response rates to nucleotide analog based therapy have been reported. Bevacizumab also has activity. We thus performed a phase II trial of gemcitabine, capecitabine, and bevacizumab in patients with metastatic renal cancer.


METHODS
Following significant hematotoxicity, dosing was modified to gemcitabine 1000 mg/m (Days 1, 8), capecitabine 1000 mg twice daily (Days 1-14), and bevacizumab 15 mg/kg (Day 1) on a 21-day cycle with evaluation every 3 cycles. Primary end point was objective response rate.


RESULTS
Twenty-nine patients were enrolled between March 2005 and May 2008. Most patients had been previously treated with a vascular endothelial growth factor receptor tyrosine kinase inhibitor. Seven patients (24%) had a partial response. Median overall and progression-free survival were 9.8 months (95% confidence interval: 6.2, 14.9) and 5.3 months (95% confidence interval: 3.9, 9.9), respectively. The regimen was well tolerated with hematologic toxicity, fatigue, and rash being most common.


CONCLUSIONS
The trial was terminated early despite not meeting criteria for success or futility because of slow accrual and because the historical response rate became irrelevant with emerging data using sequential vascular endothelial growth factor therapies. Nevertheless, the observed progression-free and overall survival compare favorably to other phase II trials in this heavily pretreated population.
Chung
Elizabeth K
EK
Section of Hematology/Oncology, Department of Medicine, University of Chicago, Chicago, IL, USA.
Posadas
Edwin M
EM
Kasza
Kristen
K
Karrison
Theodore
T
Manchen
Elizabeth
E
Hahn
Olwen M
OM
Stadler
Walter M
WM
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000009:adverse effects; D061067:Antibodies, Monoclonal, Humanized; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D000068258:Bevacizumab; D000069287:Capecitabine; D002641:Chicago; D003841:Deoxycytidine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D064420:Drug-Related Side Effects and Adverse Reactions; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D006801:Humans; D007680:Kidney Neoplasms / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D058990:Molecular Targeted Therapy / Q000009:adverse effects; D009362:Neoplasm Metastasis; D016019:Survival Analysis; D000093542:Gemcitabine
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D003841:Deoxycytidine; D000068258:Bevacizumab; D000069287:Capecitabine; D005472:Fluorouracil; D000093542:Gemcitabine
Biometrics. 1994 Jun;50(2):337-49
7980801
Cancer. 1994 Aug 1;74(3):916-9
8039119
Lancet. 2007 Dec 22;370(9605):2103-11
18156031
J Urol. 2008 Sep;180(3):867-72; discussion 872
18635226
N Engl J Med. 2003 Jul 31;349(5):427-34
12890841
Cancer. 2006 Sep 15;107(6):1273-9
16909426
Ann Oncol. 2007 Mar;18(3):576-80
17158771
J Clin Oncol. 2008 Aug 1;26(22):3702-8
18669455
J Clin Oncol. 2002 Jan 15;20(2):582-7
11786589
Cancer Chemother Pharmacol. 2008 Oct;62(5):763-8
18172648
CA Cancer J Clin. 2009 Jul-Aug;59(4):225-49
19474385
Curr Probl Cancer. 1997 Jul-Aug;21(4):185-232
9285186
Urol Oncol. 2009 Jul-Aug;27(4):363-6
18440836
J Clin Oncol. 2008 Nov 20;26(33):5422-8
18936475
Urologe A. 2004 Sep;43 Suppl 3:S145-6
15164180
J Natl Cancer Inst. 2000 Feb 2;92(3):205-16
10655437
J Urol. 2000 Feb;163(2):408-17
10647643
Cancer. 2005 Feb 1;103(3):553-8
15612026
Lancet. 2008 Aug 9;372(9637):449-56
18653228
J Clin Oncol. 2000 Jun;18(12):2419-26
10856102
N Engl J Med. 2007 Jan 11;356(2):125-34
17215530