Phase I study investigating the safety and feasibility of combining imatinib mesylate (Gleevec) with sorafenib in patients with refractory castration-resistant prostate cancer.

BACKGROUND: Determining the maximum tolerated dose (MTD) and the dose-limiting toxicity (DLT) of sorafenib (S) plus imatinib (IM) in castration-resistant prostate cancer (CRPC) patients. METHODS: Refractory CRPC patients were enrolled onto this 3+3 dose escalation designed study. Imatinib pharmacokinetics (PK) were determined on day 15, 4 h post dose with a validated LC-MS assay. RESULTS: Seventeen patients were enrolled; 10 evaluable (6 at 400 mg S qd with 300 mg IM qd (DL0) and 4 at 400 mg S bid with 300 mg IM qd (DL1)); inevaluable patients received <1 cycle. The median age was 73 (57-89); median prostatic serum antigen was 284 ng ml(-1) (11.7-9027). Median number of prior non-hormonal therapies was 3 (1-12). Dose-limiting toxicities were diarrhoea and hand-foot syndrome. Maximum tolerated dose was 400 mg S and 300 mg IM both daily. No biochemical responses were observed. Two patients had stable disease by RECIST. Median time to progression was 2 months (1-5). Median OS was 6 months (1-30+) with 3/17 patients (17%) alive at 21 months median follow-up. Ten patients had PK data suggesting that S reduced IM clearance by 55%, resulting in 77% increased exposure (P=0.005; compared with historical data). CONCLUSION: This is the first report showing that S+IM can be administered in CRPC at a dose of 400 mg S and 300 mg IM, daily.

Oral lesions in HIV-positive dental patients--one more argument for tobacco smoking cessation.

OBJECTIVE: To determine the prevalence of oral lesions associated with human immunodeficiency virus (HIV) in a population of dental patients and analyze its association with psycho-social variables and biological markers. STUDY DESIGN: The dental charts of 415 dental patients consecutively treated between May and July 2005 in a dedicated HIV dental clinic were reviewed. Oral soft tissue examinations, psycho-social and medical variables were extracted and recorded for each patient. Ethnicity, gender, HIV treatment, peripheral CD(4) counts and tobacco usage were analyzed in correlation with oral lesions associated with HIV. RESULTS: Fifty-five percent of all subjects had at least one oral lesion associated with HIV, with oral candidiasis, salivary gland enlargement and oral hairy leukoplakia being the most commonly observed conditions. Gender and ethnicity did not correlate with a higher prevalence in lesions. However, tobacco smoking correlated significantly with a higher prevalence of oral lesions, independent of CD(4) counts. CONCLUSIONS: These findings suggest that oral lesions remain commonly observed morbidities among HIV-infected dental patients independent of gender and ethnicity and that tobacco usage is a major and often underestimated risk factor for those lesions.