Regorafenib in combination with FOLFOX or FOLFIRI as first- or second-line treatment of colorectal cancer: results of a multicenter, phase Ib study.
Ann Oncol
; 24(6): 1560-7, 2013 Jun.
Article
in En
| MEDLINE
| ID: mdl-23493136
ABSTRACT
BACKGROUND:
Metastatic colorectal cancer (mCRC) is commonly treated with 5-fluorouracil, folinic acid, and oxaliplatin or irinotecan. The multitargeted kinase inhibitor, regorafenib, was combined with chemotherapy as first- or second-line treatment of mCRC to assess safety and pharmacokinetics (primary objectives) and tumor response (secondary objective). PATIENTS ANDMETHODS:
Forty-five patients were treated every 2 weeks with 5-fluorouracil 400 mg/m(2) bolus then 2400 mg/m(2) over 46 h, folinic acid 400 mg/m(2), and either oxaliplatin 85 mg/m(2) or irinotecan 180 mg/m(2). On days 4-10, patients received regorafenib 160 mg orally once daily.RESULTS:
The median duration of treatment was 108 (range 2-345 days). Treatment was stopped for adverse events or death (17 patients), disease progression (11 patients), and consent withdrawal or investigator decision (11 patients). Six patients remained on regorafenib at data cutoff (two without chemotherapy). Drug-related adverse events occurred in 44 patients [grade ≥ 3 in 32 patients mostly neutropenia (17 patients) and leukopenia, hand-foot skin reaction, and hypophosphatemia (four patients each)]. Thirty-three patients achieved disease control (partial response or stable disease) for a median of 126 (range 42-281 days).CONCLUSION:
Regorafenib had acceptable tolerability in combination with chemotherapy, with increased exposure of irinotecan and SN-38 but no significant effect on 5-fluorouracil or oxaliplatin pharmacokinetics.Key words
Full text:
1
Collection:
01-internacional
Health context:
6_ODS3_enfermedades_notrasmisibles
Database:
MEDLINE
Main subject:
Colorectal Neoplasms
/
Antineoplastic Combined Chemotherapy Protocols
Type of study:
Clinical_trials
/
Prognostic_studies
Limits:
Adolescent
/
Adult
/
Aged
/
Aged80
/
Female
/
Humans
/
Male
/
Middle aged
Language:
En
Journal:
Ann Oncol
Year:
2013
Document type:
Article