Phase I trial of pemetrexed in combination with cetuximab and concurrent radiotherapy in patients with head and neck cancer.
Ann Oncol
; 22(11): 2482-2488, 2011 Nov.
Article
in En
| MEDLINE
| ID: mdl-21363880
ABSTRACT
BACKGROUND:
We studied the combination of pemetrexed, a multi-targeted antifolate, and cetuximab, an mAb against the epidermal growth factor receptor, with radiotherapy in poor prognosis head and neck cancer. PATIENTS ANDMETHODS:
Patients received pemetrexed on days 1, 22, and 43 on a dose-escalation scheme with starting level (0) 350 mg/m(2) (level -1, 200 mg/m(2); level +1, 500 mg/m(2)) with concurrent radiotherapy (2 Gy/day) and cetuximab in two separate cohorts, not previously irradiated (A) and previously irradiated (B), who received 70 and 60-66 Gy, respectively. Genetic polymorphisms of thymidylate synthase and methylenetetrahydrofolate reductase were evaluated.RESULTS:
Thirty-two patients were enrolled. The maximum tolerated dose of pemetrexed was 500 mg/m(2) in cohort A and 350 mg/m(2) in cohort B. Prophylactic antibiotics were required. In cohort A, two dose-limiting toxicities (DLTs) occurred (febrile neutropenia), one each at levels 0 and +1. In cohort B, two DLTs occurred at level +1 (febrile neutropenia; death from perforated duodenal ulcer and sepsis). Grade 3 mucositis was common. No association of gene polymorphisms with toxicity or efficacy was evident.CONCLUSION:
The addition of pemetrexed 500 mg/m(2) to cetuximab and radiotherapy is recommended for further study in not previously irradiated patients.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Antineoplastic Combined Chemotherapy Protocols
/
Head and Neck Neoplasms
Type of study:
Prognostic_studies
Limits:
Adult
/
Aged
/
Female
/
Humans
/
Male
/
Middle aged
Language:
En
Journal:
Ann Oncol
Journal subject:
NEOPLASIAS
Year:
2011
Type:
Article