First line oral vinorelbine in elderly patients with advanced non-small-cell lung cancer

Objetivo: La actividad de la vinorelbina (VRL) en monoterapia en primera línea en pacientes concáncer de pulmón no microcítico (CPNM) ha sido contrastada en numerosos estudios. Las formulacionestanto oral en intravenosa tienen un perfil farmacocinético paralelo. Presentamos un estudio conVRL oral en pacientes (pts) ancianos con CPNM avanzado en primera línea.Material y métodos: Un global de 12 pts ≥ 70 años fueron reclutados desde Octubre 2005hasta Junio 2006. Los criterios de inclusión fueron: CPNM avanzado histológicamente confirmado,PS ≤ 2, enfermedad medible, buena reserva medular y función orgánica adecuada. La dosis del esquemaconsistió en 60 mg/m2 semanal durante 3 semanas seguidas (primer ciclo), seguido de 80 mg/m2semanal si no había toxicidad, hasta progresión o toxicidad inaceptable.Resultados: La mediana de edad fue de 74 años (rango: 71-79), todos los pts fueron varones, eigualmente todos con estadio IV. Los subtipos histológicos se distribuyeron en: adenocarcinoma en 5pts, carcinoma de células grandes en 1 pts y escamoso en 6 pts. Tres pts tenían PS 1 a la entrada en elestudio, y 9 pts PS 2, mientras que ninguno PS 0. La mediana de dosis de VRL administrada fue de 13ciclos (rango 3-23). Contando los 11 pts que recibieron el segundo ciclo, 7 de ellos pudieron escalar a80 mg/m2. Los otros 4 pts permanecieron en 60 mg/m2. No se observaron respuestas completas (RC),2 pts alcanzaron una respuesta parcial (RP), 6 pts con enfermedad estable (EE) y 4 pts con enfermedadprogresiva (EP). Respecto a la supervivencia, la mediana de seguimiento fue de 4 meses (rango 1-9meses). Hasta la fecha, no se ha alcanzado la mediana de supervivencia ni la mediana de tiempo a laprogresión. Tanto la supervivencia como la supervivencia libre de progresión (mediana de seguimiento4 meses) fue del 66% respectivamente. Respecto a la toxicidad, la tolerancia fue buena y no hubomuertes tóxicas. No se observaron toxicidades grado 4, y las toxicidades grado 3 fueron infrecuentes,con sólo 2 pacientes con neutropenia grado 3 y otros dos pacientes con astenia grado 3. Resto de lastoxicidades fueron grado 1 ó 2.Conclusiones: VRL oral puede ser una alternativa razonable a la administración intravenosa tantoen términos de actividad como de tolerabilidad en pacientes ancianos con CPNM avanzado

Purpouse: The activity of vinorelbine (VRL) as single agent in treatment-naïve inoperable nonsmall cell cancer (NSCLC) patients (pts) has been assessed in several published studies. Oral andintravenous formulation have a linearity of VRL pharmacokinetics with both routes of administration.This is a study with oral VRL in first line advanced NSCLC in elderly pts.Patients and methods: A total of 12 chemonaive elderly pts ≥ 70 years were recruited fromOctober 2005 through to June 2006. Principal inclusion criteria included histologically confirmed advancedNSCLC, performance status ≤ 2, measurable disease, appropriate bone marrow and organfunction. The dosage schedule was 60 mg/m2 once a week for three weeks (first cycle), followed if nottoxicity by 80 mg/m2 once a week, until disease progression or development of unacceptable toxicity.Results: The mean age was 74 years (range: 71 to 79), all males, and all pts stage IV. Histologysubtypes: adenocarcinoma in 5 pts, large cell carcinoma in 1 pts and squamous cell carcinoma in 6 pts.PS (ECOG) distribution was: 3 pts with PS 1, and 9 pts with PS 2. The median weekly VRL doseswas 13 (range 3-23). Out of 11 pts receiving the second cycle, 7 patients went a dose escalation to 80mg/m2. The other 4 pts remained at the 60 mg/m2 dose level. There were no complete responses (CR).Two (13%) of 12 patients achieved partial response (PR). There were 6 (50%) stable disease (SD) and4 (34%) progressive disease (PD). Respect survival, the median follow-up was 4 months (range 1-9months). Until date, the median survival time (MST) and median progression-free survival had notbeen reached; and survival and progression-free survival was 66% in both. Treatment with oral VRLin elderly patients was well tolerated, and there were no toxic deaths. No grade 4 toxicities wereobserved, and grade 3 toxicities were infrequent, exclusively neutropenia in 2 patients and asthenia inother 2 patients. Rest of toxicities were grade 1 or 2.Conclusions: Oral VRL appears to be a reasonable alternative intravenous VRL, both in terms of activity and tolerability in advanced, elderly NSCLC patients (AU)

Gemcitabine and vinorelbine followed by weekly docetaxel in patients with advanced non-small-cell lung cancer: a phase II trial of sequential chemotherapy

Objective. We conducted this phase II trial to evaluate the efficacy and toxicity of the sequential nonplatinum combination chemotherapy consisting of gemcitabine (GEM) and vinorelbine (VNR) followed by weekly docetaxel (DOC) in patients with advanced non-small-cell lung cancer (NSCLC). Patients and methods. ELIGIBILITY CRITERIA: stage IV NSCLC, Performance status =/< 2, adequate renal, hepatic and bone marrow function. Treatment consisted on: VNR 25 mg/m(2) plus gemcitabine 1000 mg/m(2), on days 1 and 8 of each 21-day cycle, followed by docetaxel 36 mg/m(2) weekly until progression or unacceptable toxicity. Results. 21 stage IV patients were enrolled. All patients are evaluable for treatment response and toxicity profile. The mean age of the patients was 63 years (range: 51 to 72) with 18 (86%) males and 3 (14%) females. Histology types were: adenocarcinoma in 8 patients (38%), large cell carcinoma in 1 patients (5%) and squamous cell carcinoma in 12 patients (57%). The majority of the patients had and ECOG PS of 1. Eight patients (38%) did not complete six cycles of gemcitabine-navelbine. The median number of cycles of gemcitabine-navelbine was 4 (range 2-6) Of the 13 patients (61%) who completed six cycles of gemcitabine-navelbine, all of them went on to receive weekly docetaxel and received at least 3 cycles, with a median number of 8 cycles (range 3- 16). The overall response rate was 33%. Respect survival, the minimum follow-up was 6 months (range, 6-25 months). The median survival time (MST) was 7.9 months, and the 1-year survival was 30%, and the median progression-free survival was 4.7 months. Toxicity was mild, well tolerated and mostly hematologic. In the GEM/VNR cycle, grade 3/4 neutropenia occurred in 14%, two patients with febrile neutropenia. Grade 3 anaemia in 1 patients (5%) and grade 3 thrombocytopenia in 1 patient (5%). Nonhematologic toxicity was also mild: 1 patient with Grade 3 skin toxicity with docetaxel, 1 patient with grade 3 infection, 2 patients with grade 3 astenia and 1 patient with a mild allergic reaction postchemotherapy treatment with docetaxel. Conclusion. The sequential triplet nonplatinum chemotherapy consisted of GEM/VNR followed by weekly DOC is active and can be administered safely in advanced NSCLC. Our results are similar with other sequential regimens and did not represent a significant improvement in the treatment of this disease (AU)

Cisplatin plus continuous infusion vinorelbine for the treatment of advanced non-small cell lung cancer: a phase I-II study.

BACKGROUND: In this Phase I/II trial, the maximumtolerated dose (MTD) and activity of cisplatin plus vinorelbine (VRL) administered in continuous infusion as first-line treatment of advanced non small cell lung cancer (NSCLC) was determined in 12 consecutive chemotherapy-naive patients with advanced NSCLC. PATIENTS AND METHODS: The dose of cisplatin was 100 mg/m(2) in all patients, and vinorelbine was administered as an initial intravenous (iv) bolus of 8 mg/m(2) on day 1 followed by a 4-day continuous iv infusion at 4 different 24 h dose levels (DLs) to be repeated every 21 days. All 12 patients (47 cycles) were evaluable for response and toxicity. RESULTS: The MTD was 8 mg/m(2) bolus followed by a continuous iv infusion of 8 mg/m(2) per day over 4 days. The dose limiting toxicities (DLT) were febrile neutropenia in 4 patients and grade 3 mucositis in 1 patient. There was less neuro-toxicity and compared to the weekly bolus scheme. There was no significant cumulative toxicity after 3 cycles. Partial responses were observed in 6 patients; an overall response rate of 50% (95% CI: 30-65%). Median time to progression was 5,5 months (95% CI: 1,5-11 months) and median survival was 11 months (95% CI: 5-20 months). CONCLUSIONS: The results demonstrate that, in this setting of first-line treatment of NSCLC, cisplatin plus vinorelbine at 8 mg/m(2) bolus followed by a continuous infusion of 8 mg/m(2) per day over 4 days is the recommended schedule. Further trials would be useful to establish activity of this combination.