[Complete response in a patient with a metastatic cutaneous melanoma]. / Respuesta completa tras tratamiento con bioquimioterapia en un caso de melanoma cutáneo diseminado.

BACKGROUND: The management of patients with disseminated disease is a difficult problem. There is currently no consensus on the standard first-line treatment for metastatic melanoma. We present a case because of his exceptional evolution. RESULTS: A 43 year old male diagnosed in 1999 with malignant melanoma stage IIA. In May 2000 hepatic and splenic metastases were detected. He received 6 cycles of biochemotherapy (cisplatin and DTIC, plus interleukin-2 and interferon-α) and another 6 cycles with single immunotherapy (interleukin-2 and interferon-α). Today, the patient is still alive and without evidence of disease. CONCLUSION: Metastatic cutaneous melanoma, sometimes presents an unusual, favourable evolution. In the near future, the methods of detection of molecular markers are expected to identify factors involved in this type of response. Furthermore, new targeted therapies may become essential to maintain this positive trend.

Respuesta completa tras tratamiento con bioquimioterapia en un caso de melanoma cutáneo diseminado / Complete response in a patient with a metastatic cutaneous melanoma

Fundamento. El pronóstico del melanoma diseminadoes muy sombrío. Actualmente no hay consensosobre el tratamiento estándar en primera línea parael melanoma metastático. Se presenta un caso por sucomportamiento excepcional.Resultados. Varón de 43 años diagnosticado en1999 de melanoma maligno estadio IIA. En mayo de2000 se objetivaron metástasis hepáticas y esplénicas.Recibió 6 ciclos de bioquimioterapia (cisplatino y DTICjunto con interleukina-2 e interferón-α) cada 21 días yotros 6 ciclos con inmunoterapia sola (interleukina-2 einterferón-α). Actualmente el paciente sigue vivo y sinevidencia de enfermedad.Conclusión. El melanoma cutáneo metastático, enocasiones, presenta una inusual evolución favorable. Esde esperar que los métodos de detección de marcadoresmoleculares logren determinar factores implicadosen este tipo de respuesta y que los nuevos tratamientosdirigidos consigan mantener esta tendencia positiva (AU)

Background. The management of patients withdisseminated disease is a difficult problem. Thereis currently no consensus on the standard first-linetreatment for metastatic melanoma. We present a casebecause of his exceptional evolution.Results. A 43 year old male diagnosed in 1999with malignant melanoma stage IIA. In May 2000, hepaticand splenic metastases were detected. He received6 cycles of biochemotherapy (cisplatin andDTIC, plus interleukin-2 and interferon-α) and another6 cycles with single immunotherapy (interleukin-2and interferon-α). Today, the patient is still alive andwithout evidence of disease.Conclusion. Metastatic cutaneous melanoma, sometimes,presents and unusual and favourable evolution. Inthe near future, the methods of detection of molecularmarkers are expected to identify factors involved in thistype of response. Furthermore, new targeted therapiesmay become essential to maintain this positive trend (AU)

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)

Specific alterations in the serum amino acid profile of patients with lung cancer and head and neck cancer

Objetivo: El metabolismo de los principios inmediatos está alterado en el enfermo neoplásico, loque se traduce en una concentración de aminoácidos séricos alterada. El objetivo del estudio es encontrarperfiles específicos de aminoácidos séricos en cáncer de pulmón y de cabeza y cuello.Material y métodos: En 51 pacientes con carcinoma de pulmón y cabeza y cuello sin alteracionesmetabólicas ni otras patologías concomitantes se analizan los niveles séricos basales de 27 aminoácidosdiferentes y se comparan entre ellos y con un grupo control.Resultados: Se encontraron diferencias estadísticamente significativas en pacientes con cáncerde cabeza respecto al grupo control en: cistina, ácido aspártico, 3-metil-histidina, alanina, glicina, lisina,metionina, prolina, serina, taurina, tirosina, treonina. Y en pacientes con cáncer de pulmón en: cistina,ácido aspártico, 3-metil-histidina, histidina, citrulina, ornitina, alanina, glicina, lisina, metionina,prolina, serina, taurina, tirosina, treonina.Conclusiones: La variación en los niveles séricos de determinados aminoácidos en cáncer de cabezay cuello y en cáncer de pulmón está motivado probablemente por la interacción de la neoplasiaen el metabolismo proteico del huésped. En cada tipo de tumor hay una cierta especificidad en el perfilde aminoácidos séricos que puede tener utilidad en el diagnóstico de estos tumores

Purpose: Metabolism of the immediate principles is altered in cancer patients, resulting in analtered serum concentration of amino acids. The aim of this study was to find specific serum aminoacid profiles in patients with cancer of the lung or head and neck.Material and methods: We analyzed the baseline serum levels of 27 amino acids in 51patients with cancer of the lung or head and neck with no metabolic alterations or other concomitantdisorders and compared the results with a control group.Results: Compared with the control group, patients with head cancer had significant differences incysteine, aspartic acid, 3-methyl histidine, alanine, glycine, lysine, methionine, proline, serine, taurine,tyrosine, and threonine; and patients with lung cancer in cysteine, aspartic acid, 3-methyl histidine,histidine, citrulline, ornithine, alanine, glycine, lysine, methionine, proline, serine, taurine, tyrosine,and threonine.Conclusions: Variation in serum levels of certain amino acids in head and neck cancer and lungcancer is probably caused by interaction of the neoplasm with the protein metabolism. Each type oftumor has a certain specificity in the serum amino acid profile that may be useful in the diagnosis ofthese tumors

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

Metástasis coroidea como debut de un carcinoma de pulmón no microcítico avanzado / Advanced non-small cell lung cancer (NSCLC) debuting with choroidal metastases

Presentamos la descripción del caso clínico de un paciente de 65 años con un carcinoma de pulmón no microcítico(CPNCP) avanzado que debuta con una alteración del campo visual derecho, sin otros síntomas,diagnosticándose en la exploración oftalmoscópica de metástasis coroidea, con la realización de una angiografíafluresceínica para diferenciarlo de una hemorragia o un hemangioma. Este caso destaca por el área infrecuentede metástasis y la inusual forma de presentación de este tipo de tumor

We present the clinical case of a 65 year old patient with right visual field disturbance as debut of adisseminated non-small cell lung cancer (NSCLC), without any other symptom. Ophthalmoscopy detectedchoroidal metastases, that fluorescein angiography delimited and differentiated from hemorrhage andhemangioma. The case emphasizes the infrequent production of metastases in this area by this tumor, and,above all, the unusual clinical debut

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

Changes in the serum amino acids concentrations after first cycle as a factor predictive of tumor response of chemotherapy

• Objetivo: Detectar variaciones en el perfil de AA séricos de pacientes neoplásicos sometidos a tratamientoquimioterápico, e intentar encontrar factores predictivos de respuesta tumoral.• Material y métodos: En 54 pacientes con carcinoma de pulmón, cabeza y cuello y geminales sin alteracionesmetabólicas ni otras patologías concomitantes se determinaron prospectivamente los niveles séricosbasales de 27 aa diferentes y se analizan basalmente y tras cada ciclo de quimioterapia.• Resultados: Observamos modificaciones en la mayoría de los AA medidos tras el primer ciclo de quimioterapiarespecto a su nivel basal. Estas modificaciones fueron más ostensibles en sujetos con respuesta a laquimioterapia. La variable porcentaje de incremento de los AA (calculada teniendo en cuenta la diferencia delnivel de aa tras el primer ciclo de quimioterapia respecto al nivel basal) fue significativamente superior en 17AA en sujetos respondedores frente a los no respondedores.• Conclusiones: La elevación brusca de la mayoría de los aminoácidos tras el 1º ciclo de quimioterapia,parece ser indicador predictivo precoz de respuesta tumoral

• Objective: To detect variations of the serum amino acids (AA) profile in cancer patients undergoing chemotherapy to identify factors predicting the response to treatment. • Material and methods: In 54 patients with lung, head and neck, and germ cell tumors, the circulating concentrations of 27 AA were prospectively measured at the basal line and following each chemotherapy cycle. • Results: We observed changes in the majority of the AA following the first chemotherapy cycle in relation to the basal line. These changes were greater in those patients who responded to chemotherapy. Following the first chemotherapy cycle, the per cent increase with regard to the base line was significantly greater for 17 AA in subjects responding to therapy when compared with those who did not respond. • Conclusions: In patients responding to therapy, a rapid rise of the majority of the AA following the first cycle appears to be an early indicator of tumor response to cisplatin-containing chemotherapy