A phase 2 trial of flavopiridol (Alvocidib) and cisplatin in platin-resistant ovarian and primary peritoneal carcinoma: MC0261.

PURPOSE: Based upon promising preclinical and phase 1 trial results, combined flavopiridol and cisplatin therapy was evaluated in patients with ovarian and primary peritoneal cancers. METHODS: A two cohort phase 2 trial of cisplatin (60 mg/m2 IV) immediately followed by flavopiridol (100 mg/m2 IV, 24 h infusion; 21 day cycles) was undertaken in patients with recurrent platin-sensitive or platin-resistant disease (progression>vs. ≤6 months following prior platin-based therapy). Measurable disease (RECIST)--or evaluable disease plus CA125>2X post-treatment nadir--and ECOG performance≤2 were required. RESULTS: Forty-five patients were enrolled between December 23, 2004 and February 25, 2010: 40 platin-resistant (Group 1), and 5 platin-sensitive (Group 2). In Group 1, the median number of treatment cycles was 3 (range 2-12). Only 10% of patients incurred grade 4 toxicities, but grade 3 toxicities were common (65%): neutropenia (17.5%); nausea (12.5%); vomiting, fatigue, thrombosis, anemia (10% each). Seven patients (17.5%) achieved a confirmed response (1 CR, 6 PR; median duration 118 days); ten additional patients (25%) attained maintained stable disease. Median time to progression was 4.3 months; overall survival was 16.1 months. Pilot translational studies assessed ascites flavopiridol level; surrogate marker studies were uninformative. In Group 2, although 4 of 5 patients responded (2 confirmed PRs with median time to progression, 10.8 months and median overall survival 20.6 months) the cohort was closed due to poor accrual. CONCLUSIONS: The assessed flavopiridol and cisplatin regimen displayed clinical activity in platin resistant and sensitive ovarian/primary peritoneal cancers, meriting further study.

Relationship of tobacco use to depressive disorders and suicidality among patients treated for alcohol dependence.

This population-based, retrospective cohort study examined the association of tobacco use and diagnosis of a depressive disorder (DD) and suicide attempts (SA) before and after discharge from an inpatient addiction program (IAP). All 813 Olmsted County, Minnesota residents (537 males, 276 females) admitted for the first time to the IAP for treatment of alcoholism during the period 1972-1983 were studied. Tobacco use status at admission was classified as ever (current or former use) (85.5%), never (8.6%), or missing (5.9%). Subjects were followed through 1994. Current or former use of tobacco was markedly lower among those with a prior diagnosis of DD than those without this diagnosis (73.6% vs. 89.3%, p<0.001). Although females were more likely to have a diagnosis of DD and were less likely to have ever used tobacco than males, gender did not explain the relationship between tobacco use and DD. Tobacco use status was unrelated to a DD diagnosis after discharge from the IAP and was not associated with SA.