RESUMO
BACKGROUND: Vatalanib (PTK787/ZK 222584) inhibits a few tyrosine kinases including KIT, platelet-derived growth factor receptors (PDGFRs) and vascular endothelial growth factor receptors (VEGFRs). We report efficacy and safety results of vatalanib in advanced gastrointestinal stromal tumour (GIST) resistant to imatinib or both imatinib and sunitinib. PATIENTS AND METHODS: Forty-five patients whose metastatic GIST had progressed on imatinib were enrolled. Nineteen (42.2%) patients had received also prior sunitinib. Vatalanib 1250 mg was administered orally daily. RESULTS: Eighteen patients (40.0%; 95% confidence interval (CI), 25.7-54.3%) had clinical benefit including 2 (4.4%) confirmed partial remissions (PR; duration, 9.6 and 39.4 months) and 16 (35.6%) stabilised diseases (SDs; median duration, 12.5 months; range, 6.0-35.6+ months). Twelve (46.2%) out of the 26 patients who had received prior imatinib only achieved either PR or SD compared with 6 (31.6%, all SDs) out of the 19 patients who had received prior imatinib and sunitinib (P=0.324). The median time to progression was 5.8 months (95% CI, 2.9-9.5 months) in the subset without prior sunitinib and 3.2 (95% CI, 2.1-6.0) months among those with prior imatinib and sunitinib (P=0.992). Vatalanib was generally well tolerated. CONCLUSION: Vatalanib is active despite its narrow kinome interaction spectrum in patients diagnosed with imatinib-resistant GIST or with imatinib and sunitinib-resistant GIST.
Assuntos
Antineoplásicos/uso terapêutico , Ftalazinas/uso terapêutico , Piridinas/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Benzamidas , Intervalo Livre de Doença , Resistencia a Medicamentos Antineoplásicos , Feminino , Tumores do Estroma Gastrointestinal/tratamento farmacológico , Humanos , Mesilato de Imatinib , Indóis/uso terapêutico , Masculino , Pessoa de Meia-Idade , Ftalazinas/efeitos adversos , Piperazinas/uso terapêutico , Inibidores de Proteínas Quinases/uso terapêutico , Piridinas/efeitos adversos , Pirimidinas/uso terapêutico , Pirróis/uso terapêutico , SunitinibeRESUMO
BACKGROUND: Ifosfamide and doxorubicin combination is an active regimen for patients with advanced soft tissue sarcomas (STS) but is burdened by high toxicity. A phase II trial was designed to assess the activity of continuous infusion ifosfamide and doxorubicin combination. PATIENTS AND METHODS: Thirty-four chemotherapy-naive patients with advanced STS were treated with ifosfamide (13 g/m(2)/12 days as continuous infusion) and doxorubicin (75 mg/m(2) on day 8) every 28 days with granulocyte colony-stimulating factor. RESULTS: The major toxicity was hematological: grade 3/4 neutropenia, anemia and thrombocytopenia occurred in 63, 30 and 12% of patients, respectively. The disease control rate was 68% and the median time to progression was 7.1 months. Among leiomyosarcomas, 2 partial responses and 4 stable diseases were observed. CONCLUSIONS: Our study confirms that the ifosfamide and doxorubicin combination has a very low non-hematological toxicity profile. This regimen attained a high disease control rate with moderate activity. Further investigation into leiomyosarcoma is warranted.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Doxorrubicina/administração & dosagem , Ifosfamida/administração & dosagem , Sarcoma/tratamento farmacológico , Neoplasias de Tecidos Moles/tratamento farmacológico , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Doxorrubicina/efeitos adversos , Esquema de Medicação , Feminino , Fator Estimulador de Colônias de Granulócitos/administração & dosagem , Humanos , Ifosfamida/efeitos adversos , Masculino , Pessoa de Meia-Idade , Sarcoma/patologia , Sarcoma/secundário , Neoplasias de Tecidos Moles/patologia , Neoplasias de Tecidos Moles/secundárioRESUMO
The aim of this study was to investigate the influence of histology and site of analysis (primary tumor versus lymph node) on the expression of genes involved in gemcitabine and cisplatin activity in non-small-cell lung cancer (NSCLC). Excision repair cross-complementing-1 (ERCC1), human equilibrative nucleoside transporter-1 (hENT1), deoxycytidine kinase (dCK), 5'-nucleotidase (5'-NT), cytidine deaminase (CDA) and ribonucleotide-reductase regulatory subunits (RRM1 and RRM2) were analyzed by quantitative-reverse transcription-PCR in 88 microdissected samples from 69 chemonaive patients. The results showed different patterns of expression for all studied genes, suggesting a possible stratification of the patients. No difference was observed between primary tumor and lymph node metastasis, as well as in adenocarcinoma and squamous-cell carcinoma specimens, while we found a correlation between the CDA-A79C polymorphism and gene expression levels. These data suggest a similar genetic susceptibility to gemcitabine-cisplatin regimens for squamous cell and adenocarcinoma and support the use of both lymph node and primary tumor for the expression profiling of NSCLC.
Assuntos
Carcinoma Pulmonar de Células não Pequenas/genética , Cisplatino/metabolismo , Citidina Desaminase/genética , Desoxicitidina/análogos & derivados , 5'-Nucleotidase/genética , Adenocarcinoma/enzimologia , Adenocarcinoma/genética , Carcinoma Pulmonar de Células não Pequenas/enzimologia , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma de Células Escamosas/enzimologia , Carcinoma de Células Escamosas/genética , Linhagem Celular Tumoral , Proteínas de Ligação a DNA/genética , Desoxicitidina/metabolismo , Desoxicitidina Quinase/genética , Endonucleases/genética , Transportador Equilibrativo 1 de Nucleosídeo/genética , Feminino , Perfilação da Expressão Gênica , Humanos , Neoplasias Pulmonares/enzimologia , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Metástase Linfática/genética , Masculino , Polimorfismo de Nucleotídeo Único , RNA Interferente Pequeno/farmacologia , Ribonucleosídeo Difosfato Redutase/genética , Proteínas Supressoras de Tumor/genética , GencitabinaRESUMO
BACKGROUND: despite the fact that the combination of gemcitabine (GCB) and docetaxel shows an increased benefit for disease-free survival and overall survival compared to GCB alone in patients with soft-tissue sarcoma, GCB mono-chemotherapy should be considered as a preferable option with respect to the combination because of its lower toxicity profile and the possibility of it being administered continuously for a long time period. CASE REPORT: we report a clinical case of a woman with advanced high-grade uterine leiomyosarcoma, refractory to ifosfamide, doxorubicin and trabectedin, who experienced a sustained and progressive response to GCB alone. CONCLUSIONS: GCB given as mono-chemotherapy can obtain long-lasting tumour control in patients heavily pre-treated with various chemotherapeutic regimes for uterine LMS and should be considered as a possible option for this subset of patients.