Pemetrexed/Carboplatin/Bevacizumab followed by maintenance Pemetrexed/Bevacizumab in hispanic patients with non-squamous non-small cell lung cancer: outcomes according to Thymidylate Synthase Expression
Cardona Zorrilla, Andrés Felipe (Clínica del Country (Bogotà, Colòmbia))
Rojas, Leonardo (Fundación de Investigación Clínica y Molecular en Cáncer (Bogotà, Colòmbia))
Wills, Beatriz (Clínica del Country (Bogotà, Colòmbia))
Arrieta, Oscar (Instituto Nacional de Cancerología (Ciutat de Mèxic))
Carranza, Hernán (Clínica del Country (Bogotà, Colòmbia))
Vargas, Carlos (Clínica del Country (Bogotà, Colòmbia))
Otero, Jorge (Clínica del Country (Bogotà, Colòmbia))
Cuello, Mauricio (Universidad de la República (Montevideo, Uruguai))
Corrales, Luis (Hospital San Juan de Dios (San José, Costa Rica))
Martín, Claudio (Instituto Alexander Fleming (Buenos Aires, Argentina))
Ortiz, Carlos (Clínica del Country (Bogotà, Colòmbia))
Franco Cirera, Sandra (Clínica del Country (Bogotà, Colòmbia))
Rosell, Rafael (Institut Germans Trias i Pujol. Hospital Universitari Germans Trias i Pujol)

Fecha:	2016
Resumen:	Objective: To evaluate the efficacy and safety of pemetrexed, carboplatin and bevacizumab (PCB) followed by maintenance therapy with pemetrexed and bevacizumab (PB) in chemotherapy-naïve patients with stage IV non-squamous non-small cell lung cancer (NSCLC) through the influence of thymidylate synthase (TS) protein and mRNA expression on several outcomes. The primary endpoints were the overall response rate (ORR), progression-free survival (PFS) and overall survival (OS). Methods: A cohort of 144 patients were administered pemetrexed (500 mg/m2), carboplatin (AUC, 5. 0 mg/ml/min) and bevacizumab (7. 5 mg/kg) intravenously every three weeks for up to four cycles. Maintenance PB was administered until disease progression or unacceptable toxicity. Results: One hundred forty-four Colombian patients with a median follow-up of 13. 8 months and a median number of 6 maintenance cycles (range, 1-32) were assessed. The ORR among the patients was 66% (95% CI, 47% to 79%). The median PFS and (OS) rates were 7. 9 months (95% CI, 5. 9-10. 0 months) and 21. 4 months (95% CI, 18. 3 to 24. 4 months), respectively. We documented grade 3/4 hematologic toxicities, including anemia (14%), neutropenia (8%), and thrombocytopenia (16%). The identified grade 3/4 non-hematologic toxicities were proteinuria (2%), venous thrombosis (4%), fatigue (11%), infection (6%), nephrotoxicity (2%), and sensory neuropathy (4%). No grade >3 hemorrhagic events or hypertension cases were reported. OS was significantly higher in patients with the lowest TS mRNA levels [median, 29. 6 months (95% CI, 26. 2-32. 9)] compared with those in patients with higher levels [median, 9. 3 months (95% CI, 6. 6-12. 0); p = 0. 0001]. TS expression (mRNA levels or protein expression) did not influence the treatment response. Conclusion: Overall, PCB followed by maintenance pemetrexed and bevacizumab was effective and tolerable in Hispanic patients with non-squamous NSCLC. This regimen was associated with acceptable toxicity and prolonged OS, particularly in patients with low TS expression. We found a role for Ki67 and TS expression as prognostic factors.
Nota:	Altres ajuts: FICMAC/017-2014
Derechos:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Lengua:	Anglès
Documento:	Article ; recerca ; Versió publicada
Materia:	Pulmons ; Càncer ; Tractament ; Pemetrexed ; Carboplatin ; Bevacizumab
Publicado en:	PloS one, Vol. 11 Núm. 5 (May 2016) , ISSN 1932-6203

DOI: 10.1371/journal.pone.0154293
PMID: 27191954

15 p, 1.1 MB

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Documentos de investigación > Documentos de los grupos de investigación de la UAB > Centros y grupos de investigación (producción científica) > Ciencias de la salud y biociencias > Institut d'Investigació en Ciencies de la Salut Germans Trias i Pujol (IGTP)
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