RESUMEN
The combination of capecitabine and the tyrosine kinase inhibitor erlotinib has recently been tested in patients with gemcitabine-refractory pancreatic tumors, with limited success. To understand this lack of efficacy, we studied the molecular effects of these agents in Capan-1 and Capan-2 human pancreatic resistant cancer cells. Erlotinib up-regulated thymidine phosphorylase (+50%) and downregulated dihydropyrimidine dehydrogenase (+55%) in a cell-dependent manner, thus suggesting that the combination should result in synergism. However, only mild additivity was achieved at best when combining both drugs, and several sequences tested even led to strong antagonism. Further experiments were performed to understand this lack of efficacy. We found that the fluoropyrimidine down-regulated EGFR expression by 30%, an unexpected finding resulting in a possible reduction in efficacy when cells were subsequently exposed to erlotinib. We also observed marked drug-induced over-expression of both cytosolic and extracellular vascular endothelial growth factor (VEGF) secretion, thus possibly triggering proliferation. These preliminary findings strongly suggest that these observations could be new mechanisms in the development of acquired drug resistance in pancreatic cancer cells.
Asunto(s)
Antimetabolitos Antineoplásicos/farmacología , Desoxicitidina/análogos & derivados , Resistencia a Antineoplásicos , Fluorouracilo/análogos & derivados , Inhibidores de Proteínas Quinasas/farmacología , Quinazolinas/farmacología , Capecitabina , Línea Celular Tumoral , Proliferación Celular , Desoxicitidina/farmacología , Dihidrouracilo Deshidrogenasa (NADP)/biosíntesis , Interacciones Farmacológicas , Receptores ErbB/biosíntesis , Clorhidrato de Erlotinib , Fluorouracilo/farmacología , Humanos , Neoplasias Pancreáticas , Timidina Fosforilasa/biosíntesis , Factor A de Crecimiento Endotelial Vascular/biosíntesisRESUMEN
BACKGROUND: The purpose of this study was to determine the maximum-tolerated dose (MTD) and the dose-limiting toxicity (DLT) of the 21 days carboplatin plus gemcitabine regimen in previously untreated patients with stage IV non small-cell lung cancer (NSCLC). METHODS: At least three patients were entered at each dose level. The starting dose was carboplatin AUC 4 mg/ml per min (Area Under the Curve; Calvert formula) on day 1 and gemcitabine 750 mg/m(2) on days 1 and 8. Carboplatin was increased to AUC 5 (level 3, 4) then to AUC 6 (level 5-7). Gemcitabine was increased to 875 (level 2, 3), 1000 (level 4, 5), 1250 (level 6) and finally 1500 mg/m(2) (level 7). Twenty-nine patients were entered into this phase I study. RESULTS: At dose level 6, a DLT (grade 4 thrombocytopenia) was observed in one out of six patients. At dose level 7, no DLT was observed during the first course, so the MTD was not reached. During the second course, two out of four patients presented grade 4 thrombocytopenia. None of the five patients receiving two courses at level 6 presented a DLT, so this level was retained for further phase II studies. Of the 25 patients assessable for response, five achieved partial responses with a response rate of 20% (95% CI, 7 to 41%). The median survival time was 7 months and the 1-year survival rate was 24% (95% CI, 9 to 45%). CONCLUSION: The combination of carboplatin given on day 1 and gemcitabine given on days 1 and 8 every 3 weeks seems to be an acceptable regimen. The DLT consists exclusively of severe thrombocytopenia. Despite the MTD was not reached with carboplatin AUC 6 mg/ml per min and gemcitabine 1500 mg/m(2), the recommended dose for further phase II studies is carboplatin AUC 6 mg/ml per min and gemcitabine 1250 mg/m(2).
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Desoxicitidina/análogos & derivados , Neoplasias Pulmonares/tratamiento farmacológico , Adulto , Anciano , Anemia/inducido químicamente , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Carboplatino/administración & dosificación , Carboplatino/efectos adversos , Carcinoma de Pulmón de Células no Pequeñas/patología , Carcinoma de Pulmón de Células no Pequeñas/secundario , Desoxicitidina/administración & dosificación , Desoxicitidina/efectos adversos , Relación Dosis-Respuesta a Droga , Esquema de Medicación , Femenino , Fiebre/inducido químicamente , Estudios de Seguimiento , Humanos , Infusiones Intravenosas , Neoplasias Pulmonares/patología , Masculino , Dosis Máxima Tolerada , Persona de Mediana Edad , Neutropenia/inducido químicamente , Recuento de Plaquetas , Trombocitopenia/inducido químicamente , Vómitos/inducido químicamente , GemcitabinaRESUMEN
Pulmonary smooth muscle lesions are rare explaining their imperfect understanding. Two cases of multiple pulmonary leiomyomatous lesions in patients who previously underwent surgery for benign uterine leiomyoma are reported. Literature was reviewed to know if the controversial question of benign metastasising leiomyomas could be resolved. Therapeutic possibilities of this pathology are also discussed.
Asunto(s)
Leiomioma , Neoplasias Pulmonares , Neoplasias Primarias Múltiples , Adulto , Biopsia , Femenino , Humanos , Leiomioma/diagnóstico , Leiomioma/patología , Pulmón/patología , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/secundario , Persona de Mediana Edad , Neoplasias Primarias Múltiples/diagnóstico , Neoplasias Primarias Múltiples/patología , Radiografía Torácica , Tomografía Computarizada por Rayos X , Neoplasias UterinasRESUMEN
The purpose of this study was to determine whether good-quality care for patients with lung cancer can be delivered without a full hospitalization unit. Our study included all consecutive untreated lung cancer patients admitted over a two-year period. The following criteria were analyzed retrospectively: residence, age, sex, histology, staging, treatments, administrative data during the first 6 months of treatment, place of death, and duration of last stay before death in the unit. Two hundred six patients were recorded. Twenty-eight percent of the patients had stage IIIB disease and 61% stage IV disease. The first treatment included: surgery (12%), chemotherapy (80%). During the first six months, the median number of hospitalizations was 8 and the median number of full hospitalization days was 17 compared with 6 days for one-day stays. The median duration of the first stay was 5 days whereas the duration of the last one was 3 days. During the first year, 71% of the patients dies: 36% in our unit (47% of them were inpatients for more than 6 days during their last stay). Diagnosis, initial treatment, management of treatment complications and supportive care are not compatible with weekly hospitalization. Full hospitalization is mandatory for good-quality care in a referral cancer unit.
Asunto(s)
Necesidades y Demandas de Servicios de Salud/tendencias , Departamentos de Hospitales/tendencias , Hospitalización/tendencias , Neoplasias Pulmonares/terapia , Servicio de Oncología en Hospital/tendencias , Grupo de Atención al Paciente/tendencias , Garantía de la Calidad de Atención de Salud/tendencias , Derivación y Consulta/tendencias , Adulto , Anciano , Anciano de 80 o más Años , Terapia Combinada , Femenino , Predicción , Francia , Servicios de Atención de Salud a Domicilio/tendencias , Humanos , Tiempo de Internación/tendencias , Neoplasias Pulmonares/mortalidad , Neoplasias Pulmonares/patología , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Cuidados Paliativos/tendencias , Estudios RetrospectivosAsunto(s)
Analgésicos/uso terapéutico , Neoplasias/fisiopatología , Dolor/tratamiento farmacológico , Analgésicos/efectos adversos , Analgésicos Opioides/efectos adversos , Analgésicos Opioides/uso terapéutico , Enfermedad Crónica , Relación Dosis-Respuesta a Droga , Vías de Administración de Medicamentos , Quimioterapia Combinada , Humanos , Dolor/clasificación , Dolor/etiología , Dimensión del Dolor/clasificación , Guías de Práctica Clínica como Asunto , Organización Mundial de la SaludRESUMEN
The real cost of medical consumption was compared with the proportion of medication consumption of (the) GHM n(o) 681 (homogeneous group of patients, chemotherapy for cancer in day care) in the French case mix system (PMSI). For those patients in our thoracic oncology unit (Sainte-Marguerite Hospital, Marseille, France), the real medication cost was calculated from prices paid by the hospital, then compared to the expected expenditures for the medication consumption of the GHM 681, i.e. 678 French francs (24.1% of the 225 ISA points (synthetic activity index)). Over a period of 2 months in 1998, 87 patients (mean age 63 +/- 11) had 194 chemotherapy sessions in day care, with multi-drug therapy in 38 cases. Vinorelbine or gemcitabine represented 81% of the single drug chemotherapy. In 84% of the single drug and 76% of the multi-drug chemotherapy, the real cost of medication consumption was above the allocated budget. The mean cost for single drug chemotherapy was 1722 FF and 2920 FF for multi-drug chemotherapy. The budget allocated by the PMSI shows a deficit in the most cases. To avoid a restriction in the use of some drugs, it appears that the French system of budget evaluation needs to be improved.