RESUMO
BACKGROUND: Treatment options are scarce in pretreated advanced non-small-cell lung cancer (NSCLC) patients. RAD001, an oral inhibitor of the mammalian target of rapamycin (mTOR), has shown phase I efficacy in NSCLC. METHODS: Stage IIIb or IV NSCLC patients, with two or fewer prior chemotherapy regimens, one platinum based (stratum 1) or both chemotherapy and epidermal growth factor receptor tyrosine kinase inhibitors (stratum 2), received RAD001 10 mg/day until progression or unacceptable toxicity. Primary objective was overall response rate (ORR). Analyses of markers associated with the mTOR pathway were carried out on archival tumor from a subgroup using immunohistochemistry (IHC) and direct mutation sequencing. RESULTS: Eighty-five patients were enrolled, 42 in stratum 1 and 43 in stratum. ORR was 4.7% (7.1% stratum 1; 2.3% stratum 2). Overall disease control rate was 47.1%. Median progression-free survivals (PFSs) were 2.6 (stratum 1) and 2.7 months (stratum 2). Common > or =grade 3 events were fatigue, dyspnea, stomatitis, anemia, and thrombocytopenia. Pneumonitis, probably or possibly related, mainly grade 1/2, occurred in 25%. Cox regression analysis of IHC scores found that only phospho AKT (pAKT) was a significant independent predictor of worse PFS. CONCLUSIONS: RAD001 10 mg/day was well tolerated, showing modest clinical activity in pretreated NSCLC. Evaluation of RAD001 plus standard therapy for metastatic NSCLC continues.
Assuntos
Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Receptores ErbB/antagonistas & inibidores , Imunossupressores/uso terapêutico , Neoplasias Pulmonares/tratamento farmacológico , Sirolimo/análogos & derivados , Adulto , Idoso , Anemia/induzido quimicamente , Antineoplásicos/administração & dosagem , Antineoplásicos/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/patologia , Intervalo Livre de Doença , Dispneia/induzido quimicamente , Everolimo , Fadiga/induzido quimicamente , Feminino , Seguimentos , Humanos , Imuno-Histoquímica , Imunossupressores/efeitos adversos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Pneumonia/induzido quimicamente , Proteínas Proto-Oncogênicas c-akt/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo , Análise de Regressão , Sirolimo/efeitos adversos , Sirolimo/uso terapêutico , Estomatite/induzido quimicamente , Trombocitopenia/induzido quimicamente , Fatores de Tempo , Resultado do TratamentoRESUMO
The thermal structure of the upper atmosphere of Mars has been theoretically investigated. The exospheric temperature, for a pure CO(2) model atmosphere, lies between 400 degrees and 700 degrees K. The origin of the Martian atmosphere is discussed in the light of these results.
