Phase I study of everolimus, cetuximab and irinotecan as second-line therapy in metastatic colorectal cancer.
OBJECTIVE
To evaluate feasible doses of weekly everolimus and irinotecan given with cetuximab for previously treated metastatic colorectal cancer (mCRC).


METHODS
Adults with mCRC that progressed after 5-fluorouracil or capecitabine-plus-oxaliplatin were treated using a sequential dose escalation scheme. Dosing decisions were based on the probability of experiencing a dose-limiting toxicity (DLT) during the first two 21-day treatment cycles.


RESULTS
Patients received everolimus 30 mg/week plus irinotecan 350 mg/m2 q3w (n=5; dose A1) or everolimus 30 mg/week plus irinotecan 250 mg/m2 q3w (n=14; dose B1). Among patients evaluable for the maximum tolerated dose, two out of four in A1 and one out of eight in B1 experienced four DLTs. The trial was terminated early based on changes in clinical practice and emerging data on everolimus dosing.


CONCLUSIONS
The feasible doses of everolimus and irinotecan administered with cetuximab as second-line therapy in mCRC were 30 mg/week and 250 mg/m2, respectively.
David Geffen School of Medicine at University of California, Los Angeles, Santa Monica, CA, U.S.A. jrhecht@mednet.ucla.edu.
J Randolph
JR
Hecht
University of California at San Diego, Moores Cancer Center, La Jolla, CA, U.S.A.
Tony R
TR
Reid
University of Texas MD Anderson Cancer Center, Houston, TX, U.S.A.
Christopher R
CR
Garrett
Highlands Oncology Group, Fayetteville, AR, U.S.A.
J Thaddeus
JT
Beck
Leavey Cancer Center, Northridge, CA, U.S.A.
Sheldon J
SJ
Davidson
London Regional Cancer Centre, London, ON, Canada.
Mary J
MJ
Mackenzie
Novartis Pharma AG, Postfach, Basel, Switzerland.
Ulrike
U
Brandt
Novartis Pharmaceuticals Corporation, East Hanover, NJ, U.S.A.
Syed
S
Rizvi
Huntsman Cancer Institute, Salt Lake City, UT, U.S.A.
Sunil
S
Sharma
D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives; D000068818:Cetuximab; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000473:pathology; D000068338:Everolimus; D005260:Female; D006801:Humans; D000077146:Irinotecan; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009362:Neoplasm Metastasis; D011518:Proto-Oncogene Proteins / Q000235:genetics; D016283:Proto-Oncogene Proteins p21(ras); D020123:Sirolimus / Q000008:administration & dosage / Q000031:analogs & derivatives; D018631:ras Proteins / Q000235:genetics
D061067:Antibodies, Monoclonal, Humanized; C117307:KRAS protein, human; D011518:Proto-Oncogene Proteins; D000077146:Irinotecan; D000068338:Everolimus; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins; D000068818:Cetuximab; D020123:Sirolimus; D002166:Camptothecin
Dose determination; EGFR monoclonal antibody; mTOR inhibitor; targeted-therapy