Phase 1 study of oral TAS-102 in patients with refractory metastatic colorectal cancer.
Cancer Chemother Pharmacol
; 76(5): 925-32, 2015 Nov.
Article
in En
| MEDLINE
| ID: mdl-26370544
ABSTRACT
PURPOSE:
To evaluate safety of TAS-102 administered twice daily (bid) on days 1-5 and 8-12 of a 4-week cycle, confirm feasibility of the Japanese recommended dose (RD), 35 mg/m(2), in Western patients with metastatic colorectal cancer (mCRC) refractory to standard chemotherapies, and describe preliminary antitumor activity.METHODS:
This open-label, dose-escalation phase 1 study was conducted at four US centers. Patients were enrolled into two sequential cohorts [30 (cohort 1) or 35 mg/m(2)/dose bid (cohort 2)]; dose-limiting toxicities (DLT) were evaluated during cycle 1 in dose-escalation cohorts. At RD, 15 additional patients were enrolled in an expansion cohort.RESULTS:
Patients (N = 27) with refractory mCRC received TAS-102; 74 % had received ≥4 prior regimens. DLT was not observed in three patients in cohort 1, and was in one out of nine patients in cohort 2 (grade 3 febrile neutropenia). Therefore, RD was identified as 35 mg/m(2) bid. At RD, fatigue (63 %), gastrointestinal disturbances and nausea (46 %), vomiting (46 %), and diarrhea (42 %) were common but rarely grade 3/4. Grade 3/4 nausea, vomiting, and diarrhea occurred at 4 % each. Grade 3/4 toxicity was predominantly hematologic [neutropenia (71 %), anemia (25 %)]; febrile neutropenia was observed in two patients. Stable disease lasting ≥6 weeks was achieved by 16 evaluable patients (70 %); median progression-free survival and overall survival were 5.3 and 7.5 months, respectively.CONCLUSIONS:
TAS-102 has an acceptable safety profile and preliminary evidence of disease stabilization in Western patients with refractory mCRC. Results from a randomized phase 3 study have shown survival benefit with disease stabilization evidence in this population.Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Uracil
/
Colorectal Neoplasms
/
Adenocarcinoma
/
Trifluridine
/
Antimetabolites, Antineoplastic
Type of study:
Clinical_trials
Limits:
Adult
/
Aged
/
Aged80
/
Female
/
Humans
/
Male
/
Middle aged
Language:
En
Journal:
Cancer Chemother Pharmacol
Year:
2015
Document type:
Article
Affiliation country:
United States