Phase I study of pemetrexed with sorafenib in advanced solid tumors.
Oncotarget
; 7(27): 42625-42638, 2016 07 05.
Article
en En
| MEDLINE
| ID: mdl-27213589
ABSTRACT
PURPOSE:
To determine if combination treatment with pemetrexed and sorafenib is safe and tolerable in patients with advanced solid tumors.RESULTS:
Thirty-seven patients were enrolled and 36 patients were treated (24 in cohort A; 12 in cohort B). The cohort A dose schedule resulted in problematic cumulative toxicity, while the cohort B dose schedule was found to be more tolerable. The maximum tolerated dose (MTD) was pemetrexed 750 mg/m2 every 14 days with oral sorafenib 400 mg given twice daily on days 1-5. Because dosing delays and modifications were associated with the MTD, the recommended phase II dose was declared to be pemetrexed 500 mg/m2 every 14 days with oral sorafenib 400 mg given twice daily on days 1-5. Thirty-three patients were evaluated for antitumor activity. One complete response and 4 partial responses were observed (15% overall response rate). Stable disease was seen in 15 patients (45%). Four patients had a continued response at 6 months, including 2 of 5 patients with triple-negative breast cancer. EXPERIMENTALDESIGN:
A phase I trial employing a standard 3 + 3 design was conducted in patients with advanced solid tumors. Cohort A involved a novel dose escalation schema exploring doses of pemetrexed every 14 days with continuous sorafenib. Cohort B involved a modified schedule of sorafenib dosing on days 1-5 of each 14-day pemetrexed cycle. Radiographic assessments were conducted every 8 weeks.CONCLUSIONS:
Pemetrexed and intermittent sorafenib therapy is a safe and tolerable combination for patients, with promising activity seen in patients with breast cancer.Palabras clave
Texto completo:
1
Base de datos:
MEDLINE
Asunto principal:
Compuestos de Fenilurea
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Niacinamida
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Pemetrexed
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Neoplasias
Tipo de estudio:
Etiology_studies
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Incidence_studies
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Observational_studies
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Risk_factors_studies
Idioma:
En
Revista:
Oncotarget
Año:
2016
Tipo del documento:
Article