A phase I trial of cisplatin plus decitabine, a new DNA-hypomethylating agent, in patients with advanced solid tumors and a follow-up early phase II evaluation in patients with inoperable non-small cell lung cancer.

The authors describe a phase I trial of cisplatin plus decitabine, a novel DNA-hypomethylating agent, in patients with advanced solid tumors, which was followed by an early phase II evaluation of the combination in patients with inoperable non-small cell lung cancer (NSCLC). In the phase I trial, cisplatin was studied at a fixed dose of 33 mg/m2, while decitabine was escalated in four (I-IV) dose escalation levels (45, 67, 90 to 120 mg/m2, respectively) in consecutive groups of at least 3 patients per dose level. Decytabine was administered to the patients as a two-hour intravenous infusion, while cisplatin was given intravenously immediately after the end of decitabine infusion. Both agents were given on days 1-3 every 21 days. Twenty-one patients were included in the phase I trial. Dose level IV (120 mg/m2 decitabine) was considered the maximum tolerated dose (MTD), while the dose-limiting toxicities were neutropenia, thrombocytopenia and mucositis. The recommended doses for phase II trials in good- and poor-risk patients were 90 (level III) and 67 mg/m2 (level II), respectively. One short-lasting partial response was observed in a patient with cervical cancer, while two minor regression were documented in a patients with NSCLC and cervical cancer, respectively. Dose level II was selected for the phase II trial in patients with inoperable NSCLC. Fourteen consecutive patients were included in this part of the study. The median age of the patients was 57 years (range, 39-75), male/female ratio of 11/3 and a median WHO performance status 1 (0-2). The stage of disease were IIIB (5) and IV (9). Prior irradiation to the chest was given in one case. A total of 30 treatment courses were evaluable for toxicity and response, with a median of 2 courses per patient (1-4). Grade 3-4 neutropenia and thrombocytopenia were observed in about half of the cases. Mucositis, diarrhea, nausea and vomiting, and skin rash were also observed in some patients. Three minor responses were documented, which lasted for 4, 16 and 36 weeks. Median survival of patients was 15 weeks (4-38). In conclusion, the cisplatin plus decitabine combination did not exhibit significant antitumor activity in patients with NSCLC at the dose and schedule applied in this trial to justify its further evaluation in this patient population.

A phase II study of recombinant interleukin-2 (IL-2) plus interferon-alfa-2A (IFN-ALFA) given subcutaneously in patients with metastatic malignant melanoma (MMM)

O objetivo deste estudo foi avaliar o perfil de toxicidade, índices de respostas objetivas e sobrevida de pacientes portadores de melanoma maligno metastático tratados com a combinação de Interleucina-2 (IL-2)e Interferon-alfa (IFN-alfa) administrados por via subcutânea (SC). Vinte e cinco pacientes com diagnóstico histopatológico de melanoma maligno metastático e doença mensurável foram tratados com IL-2 na dose de 18 milhões de unidades/m2 e IFN-alfa na dose de 3 milhões de unidades/m2 por via SC diariamente nos dias 1-5 e 8-12 de ciclos com 21 dias. Os pacientes foram todos avaliáveis quanto a toxicidade de acordo com o Common Toxicity Criteria do Instituto Nacional do Câncer dos EUA (CTC-NCI), enquanto que as respostas foram codificadas segundo os critérios da OMS. Os pacientes não haviam recebido tratamento químico, rádio ou imunoterápico prévio. Uma mediana de 3 (2-4) ciclos foram administrados. A toxicidade consistiu sobretudo de fadiga, artralgia, mialgias, febre e calafrios e retenção líquida. Não foram observadas toxicidades com risco severo de óbito. Quatro dos 25 pacientes (17 por cento) apresentaram respostas objetivas. Em 2 destes casos foi possível a ressecção completa de massas residuais pós-tratamento imunoterápico, com remissões mantidas por 6 e 24+ meses, respectivamente. Nos outros 2 casos com resposta parcial, progressão clínica foi observada após 7 e 8 meses, respectivamente. Os pacientes que não responderam inicialmente ou apresentaram progressão posterior foram ao óbito após um seguimento mediano de 3 (1-7) meses. Em conclusão, a combinação de IL-2 e IFN-alfa por via SC produziu respostas limitadas em pacientes com melanoma maligno metastático. Ainda que a toxicidade tenha sido manejável, os resultados acima descritos não recomendam esta abordagem para uso clínico de rotina.

Pneumonia por Mycoplasma pneumoniae: relato de um caso com insuficiencia respiratoria aguda. / Mycoplasma pneumoniae infection associated with acute pulmonary insufficiency. Report of a case

Um homem de 29 anos de idade, previamente higido, apresentou severa pneumonia com insufuciencia respiratoria aguda. Estudos sorologicos indicaram infeccao por Mycoplasma pneumoniae. O tratamento com doxiciclina foi bem sucedido