PURPOSE Despite undergoing allogeneic hematopoietic stem cell transplantation (HCT), patients with acute myeloid leukemia (AML) with internal tandem duplication mutation in the FMS-like tyrosine kinase 3 gene ( FLT3-ITD) have a poor prognosis, frequently relapse, and die as a result of AML. It is currently unknown whether a maintenance therapy using FLT3 inhibitors, such as the multitargeted tyrosine kinase inhibitor sorafenib, improves outcome after HCT. PATIENTS AND METHODS In a randomized, placebo-controlled, double-blind phase II trial (SORMAIN; German Clinical Trials Register: DRKS00000591), 83 adult patients with FLT3-ITD–positive AML in complete hematologic remission after HCT were randomly assigned to receive for 24 months either the multitargeted and FLT3-kinase inhibitor sorafenib (n = 43) or placebo (n = 40 placebo). Relapse-free survival (RFS) was the primary endpoint of this trial. Relapse was defined as relapse or death, whatever occurred first. RESULTS With a median follow-up of 41.8 months, the hazard ratio (HR) for relapse or death in the sorafenib group versus placebo group was 0.39 (95% CI, 0.18 to 0.85; log-rank P = .013). The 24-month RFS probability was 53.3% (95% CI, 0.36 to 0.68) with placebo versus 85.0% (95% CI, 0.70 to 0.93) with sorafenib (HR, 0.256; 95% CI, 0.10 to 0.65; log-rank P = .002). Exploratory data show that patients with undetectable minimal residual disease (MRD) before HCT and those with detectable MRD after HCT derive the strongest benefit from sorafenib. CONCLUSION Sorafenib maintenance therapy reduces the risk of relapse and death after HCT for FLT3-ITD–positive AML.

No abstract

Female gender is a significant independent favorable prognostic factor in lung cancer. To study the possible role of sex hormones in lung cancer, the expression of sex-steroid receptors and the glucocorticoid receptor was investigated in 29 lung-cancer cell lines stemming from small-cell lung cancer (SCLC) and non-small-cell lung cancer (NSCLC) by means of immunocytochemistry, ligand-binding assays and RNA expression via polymerase chain reaction. In at least 2 methods of investigation, NSCLC cell lines showed a low expression of estrogen receptor in 6, progesterone receptor in 13 and androgen receptor in I2 out of 17 cases examined; sex-steroidreceptor expression was virtually absent in SCLC cell lines. The glucocorticoid receptor was expressed in all 29 cell lines studied. Additionally, 52 tumor samples from primary lung cancer were investigated for their receptor expression by means of immunohistochernistry. Among patients with primary lung-cancer sex-steroid-receptor expression in tumor biopsies was detected most frequently in female patients (in 69% of I6 cases, vs. 42% of 36 tumors from men) and in patients with adenocarcinoma. Further research will focus on these subgroups. lmmunohistology is a feasible method of studying steroid-receptor expression in lung cancer.o 1996 Wiley-Lhs, Inc.Analyses of large clinical trials have shown that female gender is a significant independent favorable prognostic factor in small-cell lung cancer (Albain et al., 1990;Johnson et al., 1988). Further multivariate analysis of a German multicenter study comprising 766 patients revealed significance only for women under the age of 60 years (Wolf et al., 1991). Two studies of patients with unresectable non-small-cell lung cancer who were treated with chemotherapy also showed a longer survival rate for women (O'Connell et al., 1986;Finkelstein et al., 1986).To determine the influence and possible therapeutical value of sex hormones in lung cancer, we decided to study the expression of their receptors in lung-cancer cell lines and tumor biopsies, since these are a prerequisite for steroid action. There are basically 3 methods for the detection of steroid-hormone receptors: gene expression, binding assays and immunohistochemistry. The gene expression of receptors has not been investigated in lung cancer so far. Binding assays which use radioactive ligands in whole-cell or cytosolic assays are the standard method for studying receptor expression. Immunohistochemistry uses monoclonal antibodies and has been well established for the detection of estrogen receptors and progesterone receptors in breast cancer. Numerous studies have shown a close correlation between immunocytochemical methods and binding assays in mammary carcinoma (Charpin et UL, 1986).The diagnosis of lung cancer is made predominantly on small bronchoscopic biopsies or cytological specimens. Therefore binding assays for which large amounts of fresh tissue have to be provided cannot readily be performed. Immunohistochemistry may overcome this problem, since this method ...

No abstract