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1.
Lung Cancer ; 61(1): 73-81, 2008 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-18243402

RESUMEN

PURPOSE: To evaluate response rate, toxicity and epidermal growth factor (EGFR) mutations and gene copy number as outcome predictive factors in Italian patients with non-small cell lung cancer (NSCLC) treated with gefitinib (Iressa) in an expanded access program (EAP). PATIENTS AND METHODS: A total of 137 patients with advanced NSCLC received gefitinib as first line treatment or after failure of chemotherapy. In 43 cases, tissue specimens were available for EGFR status evaluation: immunohistochemical (IHC) for EGFR, fluorescence in situ hybridisation (FISH) or Chromogenic in situ hybridisation (CISH)-(ISH) analysis for EGFR and HER2 gene copy number, and PCR-DNA sequencing for mutational analysis of EGFR were performed. RESULTS: In the study population, response rate (PR) was 13%; disease stabilization (DS) 26%; overall disease control rate 39%; median survival 6.3 months and time to progression 2.7 months. Toxicity was mild (G3 skin toxicity in 3% and G3 liver toxicity in 4% of patients). An EGFR-mutation was detected in 9/43 patients: Eight deletions in exon 19 and 1 missense mutation in exon 21. Increased gene copy number for EGFR and/or HER2 was detected in 17/43 patients. Response rate was significantly higher in women, non-smokers, in mutation carriers than in wild type carriers, in EGFR-trisomy/polysomy carriers and HER2-trisomy/polysomy carriers. CONCLUSIONS: In this study, response rate and toxicity to gefitinib treatment were consistent with previously reported data for whites. Female gender, absence of smoking history, EGFR-mutations, EGFR and HER2-polysomy were significantly associated with response to gefitinib therapy in NSCLC patients.


Asunto(s)
Antineoplásicos/uso terapéutico , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Receptores ErbB/genética , Neoplasias Pulmonares/tratamiento farmacológico , Quinazolinas/uso terapéutico , Adulto , Anciano , Anciano de 80 o más Años , Carcinoma de Pulmón de Células no Pequeñas/genética , Femenino , Gefitinib , Dosificación de Gen , Humanos , Inmunohistoquímica , Hibridación Fluorescente in Situ , Neoplasias Pulmonares/genética , Masculino , Persona de Mediana Edad , Mutación , Reacción en Cadena de la Polimerasa , Pronóstico , Resultado del Tratamiento
2.
Mol Cancer Ther ; 6(4): 1223-9, 2007 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-17406029

RESUMEN

In non-small cell lung cancer (NSCLC), epidermal growth factor receptor (EGFR) mutational analysis is an excellent predictor of responsiveness to treatment with tyrosine kinase inhibitors, such as gefitinib. In up to 80% of NSCLCs, cytologic samples or endoscopic biopsies are the only specimens available for molecular analysis, but PCR amplification of DNA from small fixed and paraffin-embedded samples may create artifactual mutations. Fluorescence in situ hybridization (FISH) of EGFR and HER2 has been proposed as an alternative method of analysis. This project aimed to determine the optimal scoring method for FISH or chromogenic in situ hybridization (CISH) assays when analyzing small NSCLC samples to predict response. FISH or CISH analysis of EGFR and HER2 genes was done on 42 small samples derived from NSCLC patients treated with gefitinib. EGFR mutational analysis was done after quantity and quality controls of DNA. In seven of seven cases, a balanced increase in EGFR gene and chromosome 7 number was found to correlate with the presence of specific EGFR mutations. In addition, seven of seven cases with balanced EGFR/HER2 polysomy and two of three cases with balanced EGFR/HER2 trisomy responded to gefitinib (75% of responders). Instead, the EGFR mutations predicted only 7 of 12 (58%) of gefitinib-responsive patients. When only endoscopic biopsies or cytologic specimens are available, we propose using FISH/CISH for EGFR and HER2 as the test of choice for selecting patients for treatment with gefitinib and to consider as negative predictive factor the absence of EGFR/HER2 gene gain.


Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Receptores ErbB/genética , Hibridación Fluorescente in Situ/métodos , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/patología , Quinazolinas/uso terapéutico , Receptor ErbB-2/genética , Adulto , Anciano , Antineoplásicos/uso terapéutico , Secuencia de Bases , Biopsia , Carcinoma de Pulmón de Células no Pequeñas/diagnóstico , Carcinoma de Pulmón de Células no Pequeñas/patología , Análisis Mutacional de ADN , Exones/genética , Femenino , Gefitinib , Dosificación de Gen , Humanos , Estimación de Kaplan-Meier , Neoplasias Pulmonares/diagnóstico , Masculino , Persona de Mediana Edad , Datos de Secuencia Molecular , Mutación/genética
3.
Lung Cancer ; 54(3): 353-7, 2006 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-17049672

RESUMEN

BACKGROUND: The incidence of non-small cell lung cancer (NSCLC) is increasing among the elderly representing about 30% of NSCLC patients over 70 years old. The aim of this study was to evaluate the response, survival and tolerability of a modified schedule with cisplatin-vinorelbine in elderly patients with advanced NSCLC. METHODS: Between November 2001 and March 2003, 30 patients were included into the study. Median age was 73 (range 70-77). Male/female 27/3 (90%/10%); 60% of patients were stage IV at diagnosis and only one patient presented with brain metastasis. Treatment consisted of cisplatin 30 mg/m(2) on days 1 and 8, and vinorelbine 25 mg/m(2) on days 1 and 8 every 21 days. RESULTS: A total of 120 cycles were administered with a median of four cycles per patient. The most relevant WHO toxicities were: neutropenia grade 3 in 6 (20%) patients and grade 4 in 13 (43%) patients. There were three (10%) treatment-related deaths: two caused by neutropenic fever and one due to acute pulmonary oedema. No other relevant hematological and non-hematological toxicities occurred. By intention-to-treat analysis, 10 patients (33%) showed stable disease and 10 patients (33%) showed a partial response while 10 patients (33%) showed treatment failure. Median survival time was 7.4 months; 1-year survival was 36.6% and median time to progression was 5.14 months. CONCLUSION: At this dose and schedule, the combination of vinorelbine and cisplatin obtained a response rate and survival comparable to the most active regimens. Non-hematologic toxicity was mild while neutropenia was the most relevant toxicity.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Cisplatino/administración & dosificación , Neoplasias Pulmonares/tratamiento farmacológico , Vinblastina/análogos & derivados , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Carcinoma de Pulmón de Células no Pequeñas/patología , Cisplatino/efectos adversos , Femenino , Humanos , Neoplasias Pulmonares/patología , Masculino , Estadificación de Neoplasias , Resultado del Tratamiento , Vinblastina/administración & dosificación , Vinblastina/efectos adversos , Vinorelbina
4.
Cancer Chemother Pharmacol ; 58(2): 203-9, 2006 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-16331497

RESUMEN

PURPOSE: The safety and efficacy of a combined regimen of weekly paclitaxel and gemcitabine was tested in patients with refractory and sensitive small-cell lung cancer (SCLC). METHODS: Treatment consisted of paclitaxel 80 mg/m(2) on days 1, 8, 15 and gemcitabine 1,000 mg/m(2) on days 1 and 8 every 3 weeks. Of the 31 patients enrolled, 10 had refractory and 21 had sensitive disease. Objective responses occurred in 8 patients (26%), including 2 out of 10 patients with refractory- and 6 out of 21 patients with sensitive SCLC. Median time to progression and median survival were 9.4 and 32 weeks, respectively. RESULTS: The schedule was very well tolerated, with grade 3-4 thrombocytopenia in 26% of the patients, grade 3 neutropenia in 26%, grade 3-4 asthenia in 13% and grade 1-2 sensory neuropathy in 32%. CONCLUSION: To conclude, this weekly schedule of paclitaxel and gemcitabine was found to have moderate activity in platinum-etoposide pretreated SCLC patients and a favorable toxicity profile.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Carcinoma de Células Pequeñas/tratamiento farmacológico , Neoplasias Pulmonares/tratamiento farmacológico , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Carboplatino/administración & dosificación , Cisplatino/administración & dosificación , Desoxicitidina/administración & dosificación , Desoxicitidina/análogos & derivados , Etopósido/administración & dosificación , Femenino , Humanos , Masculino , Persona de Mediana Edad , Paclitaxel/administración & dosificación , Gemcitabina
5.
Am J Clin Oncol ; 28(3): 223-6, 2005 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-15923792

RESUMEN

Aims of this study were to evaluate the activity and toxicity of gemcitabine and cisplatin combination in malignant pleural mesothelioma (MPM). Patients with histologically proven MPM, < 75 years of age, Eastern Cooperative Oncology Group (ECOG) performance status (PS) < or = 2, and measurable MPM were eligible. Patients received gemcitabine 1250 mg/m intravenously on days 1 and 8 and cisplatin 75 mg/m on day 2, every 21 days, for a maximum of 6 cycles. From May 1999 to May 2001, 35 chemonaive patients (median age, 61 years) were enrolled. A total of 177 cycles were administered (median 5 cycles; range 1 to 6). One patient was not evaluable for response and toxicity. Nine (26%) patients had partial responses, 11 (32%) patients had progressive disease, and 14 (41%) stable disease. Median survival for all patients was 13 months. Median progression-free survival was 8 months. Grade 3 (World Health Organization) nausea and vomiting occurred in 35% of patients. Grade 3/4 anemia, grade 3/4 thrombocythemia, and grade 3/4 neutropenia were assessed in 24%, 52%, and 61% of patients, respectively. All other side effects were mild. In conclusion, gemcitabine-cisplatin combination seems to be moderately active in MPM. Furthermore, at this dose and schedule, the toxicity profile could be acceptable.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Mesotelioma/tratamiento farmacológico , Neoplasias Pleurales/tratamiento farmacológico , Adulto , Anciano , Anemia/inducido químicamente , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Cisplatino/administración & dosificación , Cisplatino/efectos adversos , Desoxicitidina/administración & dosificación , Desoxicitidina/efectos adversos , Desoxicitidina/análogos & derivados , Supervivencia sin Enfermedad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Neutropenia/inducido químicamente , Análisis de Supervivencia , Trombocitosis/inducido químicamente , Resultado del Tratamiento , Gemcitabina
6.
Lung Cancer ; 47(2): 269-75, 2005 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-15639726

RESUMEN

BACKGROUND: To determine the activity and safety of a sequential regimen of cisplatin and vinorelbine followed by paclitaxel and gemcitabine in patients with advanced non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: Treatment was two cycles of cisplatin 80 mg/m(2) on day 1 and vinorelbine 30 mg/m(2) on days 1 and 8 every 3 weeks followed by two cycles of paclitaxel 175 mg/m(2) on day 1 and gemcitabine 1250 mg/m(2) on days 1 and 8 every 3 weeks. RESULTS: Fifty-five patients with inoperable NSCLC, performance status 2 or less were enrolled, including 19 patients with brain lesions. There were 23 partial responses (42%; 95% confidence interval 29-55). The median time to progression and overall survival were 5.8 and 10.3 months, respectively (6.5 and 12.8 in the patient subset without brain metastases). One-year survival rate was 47.5%. Grade III/IV neutropenia was the major side effect; it occurred in 56% of patients and was mainly limited to the first two chemotherapy cycles with cisplatin and vinorelbine. CONCLUSIONS: Sequential combination of cisplatin and vinorelbine followed by paclitaxel and gemcitabine is a manageable and active regimen for patients with NSCLC. It deserves to be tested against a standard two-drug scheme in a phase III trial.


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 , Vinblastina/análogos & derivados , Adulto , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Carcinoma de Pulmón de Células no Pequeñas/patología , Cisplatino/administración & dosificación , Desoxicitidina/administración & dosificación , Esquema de Medicación , Femenino , Humanos , Neoplasias Pulmonares/patología , Masculino , Persona de Mediana Edad , Metástasis de la Neoplasia , Neutropenia/inducido químicamente , Paclitaxel/administración & dosificación , Análisis de Supervivencia , Resultado del Tratamiento , Vinblastina/administración & dosificación , Vinorelbina , Gemcitabina
7.
Anticancer Res ; 24(4): 2567-72, 2004.
Artículo en Inglés | MEDLINE | ID: mdl-15330216

RESUMEN

This study evaluated the activity and toxicity of a weekly paclitaxel plus gemcitabine combination as second-line treatment in patients with advanced non-small cell lung cancer (NSCLC). Paclitaxel 80 mg/m2 on days 1, 8 and 15 and gemcitabine 1000 mg/m2 on days 1 and 8 every 3 weeks were administered to 34 consecutive, advanced NSCLC patients uniformly pretreated with cisplatin or carboplatin and vinorelbine. The median time interval from first- to second-line treatment was 8 weeks (range 1-72). A total of 124 cycles with a median of 3 cycles per patient were administered (range 1-6). Four patients (12%) achieved a partial response (95% confidence interval: 1-23%), 17 had stable disease (50%) and 12 progressed (37%). Three responses were observed in 14 patients showing disease response or stabilization to previous platinum therapy. The median survival was 28 weeks (range 3-91), the median progression-free survival was 12 weeks (range 3-50) and the 1-year survival rate was 23%. The toxicity profile was favorable. In conclusion, a weekly schedule of paclitaxel plus gemcitabine as a second-line regimen has moderate activity and good tolerability in NSCLC patients not refractory to previous platinum-vinorelbine treatment.


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 , Vinblastina/análogos & derivados , Adulto , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Cisplatino/administración & dosificación , Desoxicitidina/administración & dosificación , Desoxicitidina/efectos adversos , Esquema de Medicación , Femenino , Humanos , Masculino , Persona de Mediana Edad , Paclitaxel/administración & dosificación , Paclitaxel/efectos adversos , Vinblastina/administración & dosificación , Vinorelbina , Gemcitabina
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