A B S T R A C T PurposeThe purpose of this study was to evaluate the impact of carboplatin and paclitaxel in patients with advanced previously untreated thymoma and thymic carcinoma. Patients and MethodsWe conducted a prospective multicenter study in patients with unresectable thymoma (n ϭ 21) or thymic carcinoma (n ϭ 23). Patients were treated with carboplatin (area under the curve, 6) plus paclitaxel (225 mg/m 2 ) every 3 weeks for a maximum of six cycles. The primary end point of this trial was to evaluate the objective response rate. ResultsFrom February 2001 through January 2008, 46 patients were enrolled. Thirteen patients had grade 4 or greater toxicity, mostly neutropenia. Using RECIST (Response Evaluation Criteria in Solid Tumors) 1.0 criteria, three complete responses (CRs) and six partial responses (PRs; objective response rate [ORR], 42.9%; 90% CI, 24.5% to 62.8%) were observed in the thymoma cohort; 10 patients had stable disease. For patients with thymic carcinoma, no CRs and five PRs (ORR, 21.7%; 90% CI, 9.0% to 40.4%) were observed; 12 patients had stable disease. Progression-free survival (PFS) was 16.7 (95% CI, 7.2 to 19.8) and 5.0 (95% CI, 3.0 to 8.3) months for thymoma and thymic carcinoma cohorts, respectively. To date, only seven patients (33.3%) with thymoma have died, compared with 16 patients (69.6%) with thymic carcinoma. Median survival time was 20.0 months (95% CI, 5.0 to 43.6 months) for patients with thymic carcinoma, but it has not been reached for patients with thymoma. ConclusionCarboplatin plus paclitaxel has moderate clinical activity for patients with thymic malignancies, but this seems less than expected with anthracycline-based therapy. Patients with thymic carcinoma have poorer PFS and overall survival than patients with thymoma.

Verapamil inhibited CYP3A activity, with a maximum effect occurring within 10 days. Short-term administration of verapamil caused net inhibition of intestinal P-gp, whereas long-term administration of verapamil induced P-gp activity.

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Clinical Pharmacology & Therapeutics (2003) 73, P16–P16; doi:

Clinical Pharmacology & Therapeutics (2003) 73, P16–P16; doi:

Chloroquine causes pruritus similar to that seen with opiates. It has been suggested that chloroquine (C) induced pruritus may be caused by mu opiate receptor activation. We therefore examined the effect of chloroquine on pupillary size as a marker of central mu opiate receptor activation in 12 healthy subjects of African descent with prior exposure to C, 6 with and 6 without history of chloroquine‐induced pruritus. In a single blind, sequential dosing design, subjects received a single oral dose of morphine sulphate (M, 10mg), placebo (P) pills and C (600mg base). Pupillary size was evaluated before and 0.5, 1, 2, 4, 8,12 and 24 hours after dosing. Pruritus and DSST were assessed before and 0, 4, 8, 12 and 24 hours after dosing. The patients were aged 30(±4) years and had a BMI of 24(±2) kgm‐2. Historical itchers to chloroquine (H+) and historical non‐itchers (H‐) were well matched for age, BMI, liver and renal function. When the whole group (H+ and H−) was analyzed (n=12), M caused significant pupillary constriction compared to C or P (p<0.001, T test for linear mixed model). There is no significant difference when C is compared to P. Chloroquine caused itching in 66% of historical itchers (4/6) compared to 0% of non‐itchers (p<0.05, fishers exact test). We conclude that chloroquine does not cause miosis in man and direct mu opiate activation is not a likely mechanism for chloroquine‐induced pruritus. Clinical Pharmacology & Therapeutics (2004) 75, P64–P64; doi: