Treatment rationale and study design for a phase III, double-blind, placebo-controlled study of maintenance pemetrexed plus best supportive care versus best supportive care immediately following induction treatment with pemetrexed plus cisplatin for advanced nonsquamous non-small cell lung cancer.

BACKGROUND: To improve the efficacy of first-line therapy for advanced non-small cell lung cancer (NSCLC), additional maintenance chemotherapy may be given after initial induction chemotherapy in patients who did not progress during the initial treatment, rather than waiting for disease progression to administer second-line treatment. Maintenance therapy may consist of an agent that either was or was not present in the induction regimen. The antifolate pemetrexed is efficacious in combination with cisplatin for first-line treatment of advanced NSCLC and has shown efficacy as a maintenance agent in studies in which it was not included in the induction regimen. We designed a phase III study to determine if pemetrexed maintenance therapy improves progression-free survival (PFS) and overall survival (OS) after cisplatin/pemetrexed induction therapy in patients with advanced nonsquamous NSCLC. Furthermore, since evidence suggests expression levels of thymidylate synthase, the primary target of pemetrexed, may be associated with responsiveness to pemetrexed, translational research will address whether thymidylate synthase expression correlates with efficacy outcomes of pemetrexed. METHODS/DESIGN: Approximately 900 patients will receive four cycles of induction chemotherapy consisting of pemetrexed (500 mg/m2) and cisplatin (75 mg/m2) on day 1 of a 21-day cycle. Patients with an Eastern Cooperative Oncology Group performance status of 0 or 1 who have not progressed during induction therapy will randomly receive (in a 2:1 ratio) one of two double-blind maintenance regimens: pemetrexed (500 mg/m2 on day 1 of a 21-day cycle) plus best supportive care (BSC) or placebo plus BSC. The primary objective is to compare PFS between treatment arms. Secondary objectives include a fully powered analysis of OS, objective tumor response rate, patient-reported outcomes, resource utilization, and toxicity. Tumor specimens for translational research will be obtained from consenting patients before induction treatment, with a second biopsy performed in eligible patients following the induction phase. DISCUSSION: Although using a drug as maintenance therapy that was not used in the induction regimen exposes patients to an agent with a different mechanism of action, evidence suggests that continued use of an agent present in the induction regimen as maintenance therapy enables the identification of patients most likely to benefit from maintenance treatment.

Plan Integral de Tabaquismo de Andalucía 2005-2010 : Sistema Sanitario Público de Andalucía

Publicado en la página web de la Consejería de Salud: www.juntadeandalucia.es/salud (Consejería de Salud / Ciudadanía / Quiénes somos / Planes y Estrategias)

Plan Integral de Atención a las Cardiopatías de Andalucía : 2005-2009

Publicado en la página web de la Consejería de Salud: www.juntadeandalucia.es/salud (Consejería de Salud y Bienestar Social / Ciudadanía / Quiénes Somos / Planes y Estrategias / Plan Integral de Atención a las Cardiopatías de Andalucía)

Plan integral de atención a la accidentabilidad 2007-2012

Publicado en la página web de la Consejería de Igualdad, Salud y Políticas Sociales: www.juntadeandalucia.es/salud (Consejería de Igualdad, Salud y Políticas Sociales / Ciudadanía / Quiénes somos / Planes y Estrategias)

II Plan Integral de Oncología de Andalucía : 2007-2012

Publicado en la página web de la Consejería de Salud: www.juntadeandalucia.es/salud (Consejería de Salud / Ciudadanía / Quiénes somos / Planes y Estrategias). Tiene dos documentos relacionados: Prevención del cáncer y Código de buenas prácticas en comunicación.

El II Plan Integral de Diabetes desarrolla nuevas estrategias para la detección precoz y la mejora de la atención

Boletín semanal para profesionales sanitarios de la Secretaría General de Salud Pública y Participación Social de la Consejería de Salud

“La atención integral a la infancia debe enfocarse hacia la salud y no hacia la enfermedad”

Boletín semanal para profesionales sanitarios de la Secretaría General de Salud Pública y Participación Social de la Consejería de Salud

II plan integral para la inmigración en Andalucía: acción local y gestión de la diversidad

Boletín semanal para profesionales sanitarios de la Secretaría General de Salud Pública y Participación Social de la Consejería de Salud

La igualdad de género y la autonomía personal, objetivos del I plan de acción integral para las mujeres con discapacidad en Andalucía

Boletín semanal para profesionales sanitarios de la Secretaría General de Salud Pública y Participación Social de la Consejería de Salud

Calidad, equidad y perspectiva de género, claves en la atención integral a la salud de la infancia y adolescencia en Andalucía

Boletín semanal para profesionales sanitarios de la Secretaría General de Salud Pública y Participación Social de la Consejería de Salud

Differential outcome of concurrent radiotherapy plus epidermal growth factor receptor inhibitors versus radiotherapy plus cisplatin in patients with human papillomavirus-related head and neck cancer.

BACKGROUND Human papillomavirus (HPV)-related head and neck cancer has been associated with an improved prognosis in patients treated with radiotherapy (RT) +/- chemotherapy (CT); however, RT combined with epidermal growth factor receptor (EGFR) inhibitors has not been fully studied in this group of patients. METHODS Immunohistochemical expression of p16 and PCR of HPV16 DNA were retrospectively analyzed in tumor blocks from 108 stage III/IV head and neck cancer patients treated with RT+CT (56) or RT+EGFR inhibitors (52). Disease-free survival (DFS) and overall survival (OS) were analyzed by the Kaplan-Meier method. RESULTS DNA of HPV16 was found in 12 of 108 tumors (11%) and p16 positivity in 18 tumors (17%), with similar rates in both arms of treatment. After a median follow-up time of 35 months (range 6-135), p16-positive patients treated with RT+EGFR inhibitors showed improved survival compared with those treated with RT+CT (2-year OS 88% vs. 60%, HR 0.18; 95% CI 0.04 to 0.88; p = 0.01; and 2-year DFS 75% vs. 47%, HR 0.17; 95% CI 0.03 to 0.8; p = 0.01). However, no differences were observed in p16-negative patients (2-year OS 56% vs. 53%, HR 0.97; 95% CI 0.55 to 1.7; p = 0.9; and 2-year DFS 43% vs. 45%, HR 0.99; 95% CI 0.57 to 1.7; p = 0.9). CONCLUSIONS This is the first study to show that p16-positive patients may benefit more from RT+EGFR inhibitors than conventional RT+CT. These results are hypothesis-generating and should be confirmed in prospective trials.