Pemetrexed/oxaliplatin for first-line treatment of patients with advanced colorectal cancer: a phase II trial of the National Surgical Adjuvant Breast and Bowel Project Foundation Research Program.
BACKGROUND
Pemetrexed and oxaliplatin have clinical activity as single agents in colorectal cancer (response rates, 10%-17%). In this study, these drugs were used in combination as first-line therapy in a group of patients with metastatic colorectal cancer.


METHODS
Fifty-four evaluable patients were to receive pemetrexed (500 mg/m2) with folic acid and vitamin B12 supplementation and oxaliplatin (120 mg/m2) every 21 days for 6 cycles or until disease progression occurred. Patients with stable or responding disease could continue therapy beyond 6 cycles at the discretion of the investigator. Eligibility criteria included a diagnosis of untreated metastatic adenocarcinoma of the colon or rectum, measurable disease, Zubrod performance status <or=2, no adjuvant chemotherapy within 6 months, and >or=12 weeks life expectancy.


RESULTS
The confirmed clinical response rate (primary endpoint) was 29.6% (95% confidence interval [CI], 18%-48.6%), with 1 complete response and 15 partial responses. Median time to progression was 5.3 months (95% CI, 3.9-6.3 months), and median survival was 12.3 months (95% CI, 8.6-17 months). Grade 3/4 nadir neutropenia occurred in 33.3% of patients, and 3 patients experienced grade 3 febrile neutropenia or infection associated with grade 3/4 neutropenia. Grade 3/4 nadir thrombocytopenia was seen in 11.1% of patients. Only 4% of the patients developed grade 3/4 neurotoxicity.


CONCLUSIONS
This regimen of pemetrexed and oxaliplatin has activity in advanced colorectal cancer, and the toxicity profile suggests that escalation of the dose of pemetrexed in this combination may be possible.
Atkins
James N
JN
National Surgical Adjuvant Breast and Bowel Project, University of Pittsburgh Cancer Institute, Pittsburgh, PA 15212, USA.
Jacobs
Samuel A
SA
Wieand
H Samuel
HS
Smith
Roy E
RE
John
William J
WJ
Colangelo
Linda H
LH
Vogel
Victor G
VG
Kuebler
J Philip
JP
Cescon
Terrence P
TP
Miller
Barbara J
BJ
Geyer
Charles E
CE
Wolmark
Norman
N
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000473:pathology; D005260:Female; D005971:Glutamates / Q000008:administration & dosage; D006147:Guanine / Q000008:administration & dosage / Q000031:analogs & derivatives; D006801:Humans; D008297:Male; D008875:Middle Aged; D009944:Organoplatinum Compounds / Q000008:administration & dosage; D000077150:Oxaliplatin; D000068437:Pemetrexed; D016896:Treatment Outcome
D005971:Glutamates; D009944:Organoplatinum Compounds; D000068437:Pemetrexed; D000077150:Oxaliplatin; D006147:Guanine