RESUMO
Treatment outcome data generated in prospective trials are intrinsically biased due to necessary selection criteria. Therefore the results obtained may not reflect the actual impact of current treatment options for an unselected general population. We analysed the treatment modalities and the outcome in 212 consecutive patients with non small cell lung cancer stages IIIB and IV who were seen in a community based oncology group practice between 6/1995 and 6/2006. 93 presented with stage IIIB and 119 with stage IV. Chemotherapy was given to 194/212 patients (92%), 114 patients (54%) received palliative radiation at one point during treatment. Treatment consisted of chemotherapy only in 86 patients (40%) and radiation only in 6 patients. 12 patients received best supportive care only. Patients with stage IIIB have survival rates at 12, 24 and 36 months of 64%, 27% and 21% respectively and for patients with stage IV the survival rates at 12, 24 and 36 months are 40%, 19% and 11% respectively. The median survival for stages IIIB and IV is 16 and 11 months respectively. In a multivariate analysis incorporating the factors stage (IIIB vs. IV), age (<70 vs. >/=70 years) and performance status (WHO 0/1 vs. 2/3) only stage and performance status were independent factors for survival. These retrospective data concerning analysis of survival, response rates and toxicity in a community setting confirm published results of phase II-III studies and indicate that results generated in prospective trials can be transferred into routine care.
RESUMO
Neoangiogenesis has been shown to play an important role in the pathogenesis of acute myeloid leukemia (AML). Autocrine and paracrine secretion of angiogenic and hematopoietic growth factors such as vascular endothelial growth factor (VEGF) and stem cell factor (SCF) in the bone marrow microenvironment may promote proliferation and survival of leukemic blasts. This concept represented the rationale for the initiation of a multicenter phase 2 trial of SU5416, a small molecule inhibitor of phosphorylation of VEGF receptors 1 and 2, c-kit, the SCF receptor, and fms-like tyrosine kinase-3 (FLT3) in patients with advanced AML. Entered into the study were 43 patients with refractory AML or elderly patients not judged medically fit for intensive induction chemotherapy; 42 patients received at least one dose of study drug. Treatment was generally well tolerated, with nausea, headache, and bone pain the most frequent treatment-related side effects. One patient had a morphologic remission (French-American-British [FAB] criteria of complete response without normalization of blood neutrophil and platelet counts) lasting for 2 months. There were 7 patients who achieved a partial response (reduction of blasts by at least 50% in bone marrow and peripheral blood) lasting 1 to 5 months. Patients with AML blasts expressing high levels of VEGF mRNA by quantitative polymerase chain reaction (PCR) had a significantly higher response rate and reduction of bone marrow microvessel density than patients with low VEGF expression consistent with the antiangiogenic effects of SU5416.
