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The effects of itraconazole, a strong CYP3A4 inhibitor, on the steady-state pharmacokinetics of vemurafenib were evaluated in a phase 1, multicenter, open-label, fixed-sequence study. Patients with BRAFV600 mutation-positive metastatic malignancies received oral vemurafenib 960 mg twice daily on days 1 to 20 (period A) and oral vemurafenib 960 mg twice daily with oral itraconazole 200 mg once daily on days 21 to 40 (period B). A mixed-effects analysis of variance model was used to compare log-transformed area under the concentration-time curve during the dosing interval and maximum plasma concentration values for vemurafenib in 8 patients between period B (vemurafenib plus itraconazole) and period A (vemurafenib alone). Multiple doses of itraconazole increased steady-state exposure of vemurafenib by approximately 40%, with geometric least squares mean ratios (period B/period A) of 140% (90% confidence interval, 121-161) for both maximum plasma concentration and area under the concentration-time curve during the dosing interval. There was no apparent increase in incidence or severity of adverse events during coadministration of vemurafenib with itraconazole. In conclusion, coadministration of itraconazole with vemurafenib resulted in a modest increase in exposure of vemurafenib at steady state and was generally well tolerated.

Objective To identify any association between type 2 diabetes mellitus (T2DM) and survival outcomes for mucosal squamous cell carcinoma of the head and neck. An association has been demonstrated between T2DM and cancer outcomes at numerous sites, but data for the head and neck are limited. Improving our understanding of the impact that diabetes has on head and neck cancer survival is relevant for making treatment decisions and counseling patients regarding prognosis. Study Design Retrospective cohort study. Setting Academic tertiary referral head and neck cancer center. Subjects and Methods By accessing data retrospectively from prospectively collected databases at the Princess Margaret Cancer Centre, patients were studied who were treated for mucosal head and neck squamous cell cancer between January 2005 and December 2011. Collection of clinical, pathologic, and survival data was completed with an emphasis on T2DM. Results Of 2498 patients identified in the study period, 319 (12.8%) had T2DM. Five-year overall survival was not different between the diabetic (64%, 95% CI = 58%-71%) and nondiabetic (67%, 95% CI = 65%-69%; P = .078) groups. Furthermore, cause-specific survival did not demonstrate a statistically significant difference between groups (diabetic: 84%, 95% CI = 79%-88%, vs nondiabetic: 84%, 95% CI = 82%-86%; P = .67). Conclusion Despite contradictory evidence at other cancer sites, the presence of T2DM alone does not appear to adversely affect cancer survival outcomes in head and neck squamous cell cancer. This is encouraging for the diabetic patients with head and neck squamous cell cancer, and it provides guidance for the multidisciplinary team that treats them.

Background Body mass index (BMI) has been associated variably with head and neck cancer outcomes. We evaluated the association between BMI at either diagnosis or at early adulthood head and neck cancer outcomes. Methods Patients with invasive head and neck squamous cell cancer at Princess Margaret Cancer Centre in Toronto, Canada, were surveyed on tobacco and alcohol exposure, performance status, comorbidities, and BMI at diagnosis. A subset also had data collected for BMI at early adulthood. Results With a median follow-up of 2.5 years, in 1279 analyzed patients, being overweight (hazard ratio [HR], 0.55; 95% confidence interval [CI], 0.4-0.8; p = .001) at diagnosis was associated with improved survival when compared with individuals with normal weight. In contrast, underweight patients at diagnosis were associated with a worse outcome (HR, 1.89; 95% CI, 1.2-3.1; p Conclusion Being underweight at diagnosis was an independent, adverse prognostic factor, whereas being overweight conferred better prognosis. BMI in early adulthood was not associated strongly with head and neck cancer outcomes. © 2017 Wiley Periodicals, Inc. Head Neck 39: 1226-1233, 2017.

Background The purpose of this study was to determine the clinical outcomes of T4 laryngeal cancers. Methods T4 laryngeal cancers treated with curative intent from January 2003 to December 2010 were analyzed. Outcomes were evaluated in both primary radiotherapy (+/− chemotherapy) (RT/CRT) and primary surgery cohorts. Results Among the 65 primary RT/CRT and 42 primary surgery patients included, median follow-up was 4.4 years. There was a trend for improved locoregional control with surgery (74% vs 88%; p = .08). In the RT/CRT group the 3-year laryngectomy-free survival was 67%. The 2-year gastrostomy dependency rate was 23% with RT/CRT versus 6% with primary surgery (p = .07). Overall survival (OS) at 3 years was significantly lower in the RT/CRT versus primary surgery group (41% vs 70%; p < .01). Conclusion Laryngeal preservation is achieved in over two thirds of patients with primary RT/CRT. Patients with low volume minimal cartilage involvement T4 disease may be best suited to RT/CRT. © 2016 Wiley Periodicals, Inc. Head Neck, 2016