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.

Nuevas perspectivas en el tratamiento del cáncer de pulmón no microcítico: farmacogenómica / New prospectives in non-small cell lung cancer treatment: pharmacogenomics

La estrategia de tratamiento más utilizada en el cáncer de pulmón no microcítico (CPNM) avanzadoes la quimioterapia, concretamente la combinación de dos drogas, principalmente cisplatino con gemcitabina,vinorelbina, taxanos, irinotecan. En el pasado se han hecho intentos en vano de revertir la resistenciaa la quimioterapia. La supervivencia en este estadio no suele superar los 8-10 meses con eltratamiento convencional. En el presente, intentos para superar estos resultados se focalizan en la farmacogenómica,con el objetivo de individualizar la quimioterapia basado en aspectos de biología molecular,como los polimorfismos, mutaciones genéticas, y sobreexpresión de genes que pueden funcionarcomo dianas de los fármacos. La evidencia indica que algunos marcadores genéticos pueden serpredictivos de resistencia a la quimioterapia. Uno de los objetivos en investigación translacional es investigarla aplicación clínica de los sistemas de reparación del DNA. Algunos genes como ERCC1,XPD polymorphisms. RRM1, BCRA1, etc, se relacionan con resistencia a cisplatino y otras drogas

The most commonly used chemotherapy strategy in advanced non-small cell lung cancer (NSCLC)today is the combination of two drugs, mainly cisplatin with another drug (gemcitabine, vinorelbine,taxanes, irinotecan). In the last decade attempts have been made to overcome chemotherapy resistancewithout benefit in outcome. There is a “plateau” in the results which seems unable to progress beyondthe frontier of 8-10 months of median survival. At present, research in cancer survival is focused ontranslational pharmacogenomics, with the goal of providing individualized CT based on differentgenetic traits, such a polymorphisms, gen mutation and overexpresion of drug target gene transcripts,and several molecular assays can been used to tailor chemotherapy in the care of lung cancer patients.Accumulated evidence indicates that many genetic markers are related to chemotherapy resistance.One of the most important goals in translational research is to investigate the clinical use of the DNArepair pathways. Several genes such as ERCC1, XPD polymorphisms. RRM1, BCRA1, etc are relatedto cisplatin and other drugs resistance

Actualización en el tratamiento sistémico del carcinoma microcítico de pulmón / Updating the systemic treatment of lung microcytic carcinoma

Entre los pacientes con cáncer de pulmón, la proporción de aquellos del subtipo de células pequeña (CPCP)ha disminuido en la última década. La estadificación del CPCP se clasifica como enfermedad limitada (EL) yenfermedad extendida (EE). La EL se puede tratar con intención curativa con la combinación de quimioterapiay radioterapia, con una mediana de supervivencia de 18 meses aproximadamente. Los pacientes con EE sontratados primariamente con quimioterapia, con una alta tasa de respuestas globales en primera línea, que oscilade 60 a 70%, y respuestas completas del 20-30%, pero la mediana de supervivencia no suele superar los 9 meses.Esta es una revisión que presenta diversas controversias a cerca del tratamiento sistémico de esta enfermedad,siempre en el ámbito de la evidencia científica, pero desde una perspectiva crítica. Al igual que en EL, laquimioterapia debería administrarse en combinación de varios agentes a dosis terapéuticas. La quimioterapiabasada en platino permanece siendo la piedra angular del tratamiento tanto en EE como en EL. Hasta la fechano se ha demostrado un beneficio claro en supervivencia para el incremento de la intensidad de dosis, mantenimiento,o la quimioterapia a altas dosis con soporte hematopoyético. Sin embargo, la estrategia de aumentar ladensidad de dosis, es decir, de disminuir el intervalo de tiempo entre los ciclos, ha demostrado mejoría en supervivenciaen cuatro ensayo aleatorizados. Los agentes de tercera generación combinados con cisplatino, puedenser una opción válida, pero no han demostrado beneficio en supervivencia comparado con el esquema dereferencia, que es la asociación de cisplatino y etopósido. Los pacientes en recaída o refractarios tienen un malpronóstico, y basándonos en los ensayos aleatorizados, se puede recomendar topotecán como tratamiento deelección. Las drogas contra nuevas dianas terapéuticas tienen una expectativa prometedora, pero los ensayosfase III realizados hasta la fecha no han demostrado beneficio en supervivencia

Among patients with lung cancer, the proportion of those with small cell lung cancer (SCLC) type hasdecreased over the last decade. Staging of SCLC considers a limited disease and an extensive disease. Limiteddisease stage is treated for curative intent by chemotherapy and radiation therapy, with a median survival timeof approximately 18 months. Extensive disease stage is treated primarily by chemotherapy, with a high initialresponse rate of 60 to 70% and a complete response rate of 20 to 30%, but with a median survival time ofapproximately 9 months. This review poses several questions about the systemic treatment of SCLC, based onmedical evidence, but making a critical overview. In both, extensive and limited stages of SCLC, acombination of several drugs is administered in doses associated with at least moderate toxic effects in order toproduce the best results. Platinum-based chemotherapy remains the treatment mainstay in both cases.Currently, a clear benefit of dose intensity or maintenance, or of association with bone marrow transplantationhas not been observed in SCLC patients. However, the strategy of chemotherapy densification by shorteningthe cycle intervals has shown a survival increase in four randomized trials. Third generation drugs combinedwith cisplatin are possible treatment options, but they have not shown any survival advantage to date whencompared with the standard combination of cisplatin and etoposide. Relapsed or refractory SCLC have auniformly poor prognosis, being topotecan the treatment of choice. Drugs with new therapeutic targets arepromising, but they have not either shown a betterment of survival to date

Dural metastases with subdural hematoma from prostate cancer

Decribimos el caso de un paciente de 54 años de edad con cáncer de próstata avanzado con hematoma subduralno traumático secundario a metástasis durales. Había recibido previamente tratamiento hormonal y quimioterapiabasada en docetaxel. En la resonancia magnética se mostraba el hematoma subdural en el contextode metástasis leptomeníngeas y durales. Hay que destacar esta forma tan inusual de metástasis de un cáncer depróstata y el mal pronóstico que conlleva esta complicación

We reported a case of subdural effusion secondary to dural metastasis of prostatic cancer. A 54-year-old manwas referred for headache, vomiting and gait disturbance. He had undergone hormonal therapy and docetaxelbasedchemotherapy for prostatic cancer. The magnetic resonance imaging of the brain showed extensiveleptomeningeal carcinomatosis and cranial dural metastases, and subdural hematoma. This is a very raresituation and bad prognosis

Glutamina sérica como factor predictivo de insuficiencia renal en pacientes oncológicos tratados con quimioterapia basada en cisplatino / Serum glutamine as a predictive factor of renal failure in oncologic patients treated with cisplatin-based

• Propósito: La glutamina es el vehículo del nitrógeno para poder ser transportados de formano tóxica por la sangre. En insuficiencia renal se elevan sus niveles. Se pretende encontrar factorespredictivos de riesgo de desarrollar insuficiencia renal secundaria al cisplatino.• Material y métodos: 54 pacientes con diversos tumores sometidos a tratamiento quimioterápicobasado en cisplatino. Se determinaban aminoácidos plasmáticos el tercer día tras cada infusión.• Resultados: el nivel de glutamina a lo largo de los ciclos es mayor en pacientes con insuficienciarenal. la glutamina > 1000 µMol/L recogida tras el cisplatino es altamente predictiva de desarrollarinsuficiencia renal.• Conclusiones: La elevación de la glutamina plasmática tiene un alto valor predictivo de desarrollarinsuficiencia renal secundaria al cisplatino

• Purpose: Glutamine is a vehicle transporting non-toxic nitrogen in the blood. High levels ofglutamine are present in renal failure. We studied glutamine searching possible predictive factorsassociated to the development of renal failure secondary to cisplatin.• Material and methods: We studied 34 patients with different tumors treated with cisplatinbasedchemotherapy. We determined the serum amino acid three days after each infusion.• Results: Glutamine concentration along the chemotherapy cycles was higher in the patientswith renal failure. Glutamine level >1000 µM/L determined after cisplatin administration wasstrongly predictive of developing renal failure.• Conclusions: The elevation of serum glutamine has a significant predictive value of developingrenal failure secondary to cisplatin