Phase I study of pegylated interferon-alpha-2b as an adjuvant therapy in Japanese patients with malignant melanoma.

In the adjuvant setting for malignant melanoma, interferon (IFN)-α-2b and pegylated (PEG) IFN-α-2b were approved in several countries including the USA before these were approved in Japan. To resolve the "drug-lag" issue, this phase I study was designed to evaluate the safety and tolerability in Japanese patients with stage II or III malignant melanoma who had undergone surgery, by treating with PEG IFN-α-2b. As with a previously reported phase III study, patients were to receive PEG IFN-α-2b 6 µg/kg per week s.c. during an 8-week induction phase, followed by a maintenance phase at a dose of 3 µg/kg per week up to 5 years. Dose-limiting toxicity and pharmacokinetics were assessed during the initial 8 weeks. Of the nine patients enrolled, two patients had dose-limiting toxicities that resolved after discontinuation of treatment. The most frequently reported drug-related adverse events (DRAE) included pyrexia, decreased neutrophil and white blood cell counts, and arthralgia. Grade 3 DRAE included decreased neutrophil count. No deaths, serious adverse events and grade 4 adverse events were reported. Distant metastasis occurred in one patient. No apparent differences in area under the concentration-time curve and maximum observed serum concentration were observed between Japanese and historical non-Japanese pharmacokinetic data, suggesting no marked racial differences. No neutralizing antibody was detected in these patient samples. PEG IFN-α-2b was tolerated in Japanese patients, and eventually approved in Japan in May 2015 for adjuvant therapy in patients with stage III malignant melanoma. Because the number of patients was limited, further investigation would be crucial.

Relationships of craniofacial morphology and body mass index with sleep-disordered breathing in Japanese men.

OBJECTIVE/HYPOTHESIS: Obesity is an established risk factor for sleep-disordered breathing, but the impact of craniofacial morphology is uncertain. The aim of this study was to assess the impact of craniofacial morphology and body weight on sleep-disordered breathing in Japanese men. STUDY DESIGN: A cross-sectional study. METHODS: We measured body mass index, seven cephalometric variables, and 3% oxygen desaturation index recorded by a pulse oximeter in 313 Japanese men aged 20 to 65 years who attended a sleep clinic. We defined craniofacial score as the sums of quartile points (0-3) for distance from sella to nasion and that from hyoid bone to mandibular plane. RESULTS: The mean value of 3% oxygen desaturation index and odds ratios of 3% oxygen desaturation index 15 or greater progressively increased with craniofacial score as well as body mass index. Multivariate odds ratios associated with craniofacial score were higher in men with body mass index 25.0 kg/m or greater (odds ratio = 4.2, 95% confidence interval [CI] = 2.1-8.6) than in men with lower body mass index (odds ratio = 1.6, 95% CI = 0.7-3.6). CONCLUSIONS: Our results imply the importance of cephalometric assessment in overweight patients.