A randomized phase II study of raltitrexed and gefitinib versus raltitrexed alone as second line chemotherapy in patients with colorectal cancer. (1839IL/0143).
OBJECTIVE
To determine the efficacy of the addition of gefitinib to raltitrexed in patients with colorectal cancer (CRC) that have progressed after first line chemotherapy. The study also sought to explore the safety of the combination and to investigate biomarkers predictive outcome.


METHODS
A total of 76 patients were randomized to raltitrexed (3 mg/m(2) i.v.) every 21 days plus either daily gefitinib (250 mg p.o.) or placebo. The primary endpoint of the study was progression free survival (PFS). Tumor tissues were collected to determine the expression of EGFR, pEGFR, pMAPK, and pAkt.


RESULTS
Both groups were well balanced with regard to prognostic factors. Treatment was well tolerated with no increased in toxicity except diarrhea and skin rash in the combination group. There were no differences in PFS between the combination arm [63 days (95% CI: 57-84)] compared to the raltitrexed alone arm [72 days (95% CI: 59-132)], or overall survival 361 days (95% CI: 283-533 days) versus 291 days (95% CI: 255-539 days) respectively. The objective response rate was 7.9% (3 patients) (CI 95%: 1,66-21,38) versus 5.3% (2 patients) (CI 0,64-17,75), respectively. The biomarker studies were not conclusive.


CONCLUSIONS
The combination of raltitrexed and gefitinib was well tolerated although was not associated with improved progression free survival in patients with refractory CRC.
Viéitez
José María
JM
Medical Oncology Service, Hospital Universitario Central de Asturias, 33006 Oviedo, Spain. josemariavieitez@yahoo.es
Valladares
Manuel
M
Peláez
Ignacio
I
de Sande González
Luis
L
García-Foncillas
Jesús
J
García-López
José Luis
JL
García-Girón
Carlos
C
Reboredo
Margarita
M
Bovio
Humberto
H
Lacave
Angel Jiménez
AJ
D000293:Adolescent; D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000378:metabolism; D015179:Colorectal Neoplasms / Q000188:drug therapy*; D003710:Demography; D005260:Female; D000077156:Gefitinib; D006801:Humans; D008297:Male; D008875:Middle Aged; D011799:Quinazolines / Q000009:adverse effects / Q000627:therapeutic use*; D016019:Survival Analysis; D013876:Thiophenes / Q000009:adverse effects / Q000627:therapeutic use*; D016896:Treatment Outcome; D055815:Young Adult
D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D011799:Quinazolines; D013876:Thiophenes; C068874:raltitrexed; D000077156:Gefitinib