Treatment of advanced renal cell carcinoma with the combination bevacizumab/erlotinib/imatinib: a phase I/II trial.
OBJECTIVE
The aim of this study was to evaluate the efficacy and toxicity of imatinib, a platelet-derived growth factor-beta receptor antagonist, when added to the combination bevacizumab/erlotinib in the treatment of patients with advanced clear cell renal carcinoma.


METHODS
Ninety-four patients with metastatic clear cell renal carcinoma were treated with bevacizumab 10 mg/kg intravenously every 2 weeks, erlotinib 150 mg orally daily, and imatinib 400 mg orally daily. Patients were reevaluated after 8 weeks of treatment; patients with objective response or stable disease (SD) continued to receive treatment until they experienced tumor progression.


RESULTS
Fifteen of 88 evaluable patients (17%; 95% confidence interval, 10%-26%) had partial responses, whereas an additional 54 patients (61%) had SD. The median progression-free and overall survival for all patients was 8.9 months and 17.2 months, respectively. The addition of imatinib markedly increased toxicity compared with the bevacizumab/erlotinib regimen; the most common grade 3/4 toxicities were diarrhea, rash, and fatigue.


CONCLUSIONS
Bevacizumab/erlotinib/imatinib was unacceptably toxic in this group of patients. Inhibition of the PDGF receptor (PDGFR) with imatinib did not appear to improve efficacy compared retrospectively with the results of treatment with bevacizumab/erlotinib. The importance of PDGFR inhibition in the treatment of advanced clear cell renal carcinoma remains unclear. Further development of this particular combination is not planned or recommended.
Hainsworth
John D
JD
Sarah Cannon Research Institute and Tennessee Oncology, PLLC, Nashville, TN 37203, USA. jhainsworth@tnonc.com
Spigel
David R
DR
Sosman
Jeffrey A
JA
Burris
Howard A
HA
Farley
Cindy
C
Cucullu
Heather
H
Yost
Kathleen
K
Hart
Lowell L
LL
Sylvester
Linda
L
Waterhouse
David M
DM
Greco
F Anthony
FA
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 / Q000627:therapeutic use*; D001549:Benzamides; D000068258:Bevacizumab; D002292:Carcinoma, Renal Cell / Q000188:drug therapy* / Q000401:mortality; D066246:ErbB Receptors / Q000037:antagonists & inhibitors; D000069347:Erlotinib Hydrochloride; D005260:Female; D006801:Humans; D000068877:Imatinib Mesylate; D007680:Kidney Neoplasms / Q000188:drug therapy* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D010879:Piperazines / Q000008:administration & dosage / Q000009:adverse effects; D011743:Pyrimidines / Q000008:administration & dosage / Q000009:adverse effects; D011799:Quinazolines / Q000008:administration & dosage / Q000009:adverse effects; D017479:Receptors, Platelet-Derived Growth Factor / Q000037:antagonists & inhibitors; D040262:Receptors, Vascular Endothelial Growth Factor / Q000037:antagonists & inhibitors
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D001549:Benzamides; D010879:Piperazines; D011743:Pyrimidines; D011799:Quinazolines; D000068258:Bevacizumab; D000068877:Imatinib Mesylate; D000069347:Erlotinib Hydrochloride; D066246:ErbB Receptors; D017479:Receptors, Platelet-Derived Growth Factor; D040262:Receptors, Vascular Endothelial Growth Factor