RESUMEN
AIM: Ceritinib was evaluated within a compassionate use program of Italian patients. PATIENTS & METHODS: 70 patients with anaplastic lymphoma kinase-positive crizotinib-refractory advanced non-small-cell lung cancer received ceritinib. RESULTS: Overall response was 40.6%, median progression-free survival was 8.2 months and median survival was 15.5 months. Dose reduction due to treatment-related adverse events occurred in 50.8% of patients starting at 750 mg/day. No significantly different progression-free survival was observed between patients who underwent any time dose reduction (n = 38) versus those who remained on the recommended dose of 750 mg/day (n = 32; p = 0.07). CONCLUSION: The efficacy of ceritinib compassionate use program resembled that of clinical trials. Dose reductions and adjustments did not appear to negatively affect clinical outcome.
Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Inhibidores de Proteínas Quinasas/administración & dosificación , Pirimidinas/administración & dosificación , Proteínas Tirosina Quinasas Receptoras/genética , Sulfonas/administración & dosificación , Adulto , Anciano , Anciano de 80 o más Años , Quinasa de Linfoma Anaplásico , Carcinoma de Pulmón de Células no Pequeñas/genética , Carcinoma de Pulmón de Células no Pequeñas/patología , Ensayos de Uso Compasivo , Crizotinib , Supervivencia sin Enfermedad , Relación Dosis-Respuesta a Droga , Resistencia a Antineoplásicos/efectos de los fármacos , Femenino , Reordenamiento Génico , Humanos , Masculino , Persona de Mediana Edad , Mutación , Inhibidores de Proteínas Quinasas/efectos adversos , Pirazoles/administración & dosificación , Pirazoles/efectos adversos , Piridinas/administración & dosificación , Piridinas/efectos adversos , Pirimidinas/efectos adversos , Proteínas Tirosina Quinasas Receptoras/antagonistas & inhibidores , Sulfonas/efectos adversosRESUMEN
BACKGROUND: Improving results in nonsmall-cell lung cancer (NSCLC) will require the development of new drugs and strategies to combine available agents. On the basis of data indicating the activity of docetaxel as second-line therapy, a Phase II study was conducted to evaluate the efficacy and toxicity of the sequential combination of chemotherapy consisting of cisplatin (P) and gemcitabine (G) followed by docetaxel (DOC) in patients with advanced NSCLC. METHODS: Patients with 1997 TNM stage IIIB (pleural effusion)/stage IV NSCLC, performance status (PS) of 0-1, and normal organ function were eligible. Therapy consisted of P at 75 mg/m(2) on Day 1 and G 1200 mg/m(2) on Days 1 and 8 every 3 weeks for 3 cycles followed, in nonprogressive patients, by DOC 30 mg/m(2) every week for 6 consecutive weeks every 8 weeks for 2 cycles. RESULTS: Fifty-two eligible patients were enrolled (M/F, 39/13; stage IIIB/IV, 8/44; PS 0, 73%, PS 1, 27%; median age, 58 years; range, 36-73). The overall response rate was 36.5% (95% confidence interval [CI]: 23-49). The median overall survival was 11 months (95% CI: 9-13); the median progression-free survival was 6 months (95% CI: 5-7); and the 1- and 2-year survivals were 48% and 25%, respectively. One- and 2-year progression-free survivals were 12% and 8%, respectively. Both phases of the treatment protocol were well tolerated. CONCLUSIONS: P/G followed by weekly DOC is well tolerated and active as first-line therapy for NSCLC patients and provides a feasible chemotherapeutic option in this clinical setting.