BACKGROUNDApalutamide, a competitive inhibitor of the androgen receptor, is under development for the treatment of prostate cancer. We evaluated the efficacy of apalutamide in men with nonmetastatic castration-resistant prostate cancer who were at high risk for the development of metastasis. METHODSWe conducted a double-blind, placebo-controlled, phase 3 trial involving men with nonmetastatic castration-resistant prostate cancer and a prostate-specific antigen doubling time of 10 months or less. Patients were randomly assigned, in a 2:1 ratio, to receive apalutamide (240 mg per day) or placebo. All the patients continued to receive androgen-deprivation therapy. The primary end point was metastasis-free survival, which was defined as the time from randomization to the first detection of distant metastasis on imaging or death. RESULTSA total of 1207 men underwent randomization (806 to the apalutamide group and 401 to the placebo group). In the planned primary analysis, which was performed after 378 events had occurred, median metastasis-free survival was 40.5 months in the apalutamide group as compared with 16.2 months in the placebo group (hazard ratio for metastasis or death, 0.28; 95% confidence interval [CI], 0.23 to 0.35; P<0.001). Time to symptomatic progression was significantly longer with apalutamide than with placebo (hazard ratio, 0.45; 95% CI, 0.32 to 0.63; P<0.001). The rate of adverse events leading to discontinuation of the trial regimen was 10.6% in the apalutamide group and 7.0% in the placebo group. The following adverse events occurred at a higher rate with apalutamide than with placebo: rash (23.8% vs. 5.5%), hypothyroidism (8.1% vs. 2.0%), and fracture (11.7% vs. 6.5%). CONCLUSIONSAmong men with nonmetastatic castration-resistant prostate cancer, metastasisfree survival and time to symptomatic progression were significantly longer with apalutamide than with placebo. (Funded by Janssen Research and Development; SPARTAN ClinicalTrials.gov number, NCT01946204.)

The combination of zidovudine and interferon alfa has activity against adult T-cell leukemia-lymphoma, even in patients in whom prior cytotoxic therapy has failed. This regimen should be evaluated further for its role in the treatment of adult T-cell leukemia-lymphoma.

SummaryThrombocytopenia can be a complication of hepatitis C viral (HCV) infection. However, there is little published data regarding the clinical and laboratory manifestations of HCV-related thrombocytopenia (HCV-TP) compared with adult chronic immune thrombocytopenic purpura (CITP). We reviewed the medical records for all patients evaluated for chronic thrombocytopenia by the Haematology Service between January 1996 and June 2000. All patients were screened for HCV infection at the time of initial diagnosis. Of 250 patients who fulfilled American Society of Hematology criteria for CITP, 76 (30%) were HCV seropositive. HCV-TP patients were older [mean age (±SD) 54AE9 ± 8 years vs. 40AE3 ± 8 years, P £ 0AE001] and equally distributed between both sexes. HCV-TP patients had less severe thrombocytopenia, defined as platelet count £10 · 10 9 /l (4% vs. 46% for CITP, P £ 0AE001). However, 56 (74%) had a platelet count £50 · 10 9 /l. Symptoms and signs of thrombocytopenia were less frequent in HCV-TP, but major bleeding was more frequent (25% vs. 10%, P ¼ 0AE0059). Serum cryoglobulins and anticardiolipin antibodies were more frequent in HCV-TP (90% and 62% respectively), but rare in CITP (7% and 15%, P £ 0AE001 compared with HCV-TP). HCV infection can be associated with significant thrombocytopenia and appears to be a distinct clinical entity.

DaunoXome has an improved pharmacokinetic profile compared with free daunorubicin, and is well tolerated. DaunoXome can be given safely at doses up to 60 mg/m2 every 2 weeks and has significant antitumor activity in patients with AIDS-KS.