Safety and efficacy of the combination of erlotinib and sirolimus for the treatment of metastatic renal cell carcinoma after failure of sunitinib or sorafenib.
BACKGROUND
The mammalian target of rapamycin (mTOR) is an important therapeutic target in the treatment of renal cell carcinoma (RCC). Pre-clinical data indicate that the combined inhibition of both the epidermal growth factor receptor and mTOR results in enhanced anticancer activity.


METHODS
All patients had metastatic RCC with progression after treatment with sunitinib and/or sorafenib. Treatment consisted of erlotinib 150 mg orally once a day starting on day 1 and sirolimus 6 mg orally on day 8 followed by 2 mg daily, adjusted according to blood levels.


RESULTS
A total of 25 patients were enrolled between July 2006 and March 2008. The median progression-free survival (PFS) was 12 weeks (95% CI 5.9-18.1) and median overall survival (OS) 40 weeks (95% CI 0-85.7). No confirmed complete or partial responses were observed, but stable disease >6 months was noted in 21.8% (95% CI 4.9-38.6) of patients. The most common adverse events were rash and diarrhoea. There was no correlation between erlotinib, OSI-420 (days 8 and 15) or sirolimus (days 15 and 29) blood levels and PFS or OS.


CONCLUSIONS
The combination of sirolimus and erlotinib for RCC failed to demonstrate an advantage over available single-agent therapy in the second-line setting.
Flaig
T W
TW
Division of Medical Oncology, Department of Medicine, University of Colorado Denver School of Medicine, Mail Stop 8117, 12801 East 17th Avenue Room 8117, Aurora, CO 80045, USA. Thomas.Flaig@UCDenver.edu
Costa
L J
LJ
Gustafson
D L
DL
Breaker
K
K
Schultz
M K
MK
Crighton
F
F
Kim
F J
FJ
Drabkin
H
H
D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D001557:Benzenesulfonates / Q000008:administration & dosage; D002292:Carcinoma, Renal Cell / Q000188:drug therapy* / Q000473:pathology; D002853:Chromatography, Liquid; D018572:Disease-Free Survival; D000069347:Erlotinib Hydrochloride; D005260:Female; D006801:Humans; D007211:Indoles / Q000008:administration & dosage; D007680:Kidney Neoplasms / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009536:Niacinamide / Q000031:analogs & derivatives; D010671:Phenylurea Compounds; D011725:Pyridines / Q000008:administration & dosage; D011758:Pyrroles / Q000008:administration & dosage; D011799:Quinazolines / Q000008:administration & dosage; D020123:Sirolimus / Q000008:administration & dosage; D000077157:Sorafenib; D000077210:Sunitinib; D053719:Tandem Mass Spectrometry
D001557:Benzenesulfonates; D007211:Indoles; D010671:Phenylurea Compounds; D011725:Pyridines; D011758:Pyrroles; D011799:Quinazolines; D009536:Niacinamide; D000077157:Sorafenib; D000069347:Erlotinib Hydrochloride; D000077210:Sunitinib; D020123:Sirolimus
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