Burden of illness in fibromyalgia patients with comorbid depression.

OBJECTIVES: To assess the burden of fibromyalgia (FM) in patients with FM taking antidepressant medication for comorbid depression. METHODS: Symptom burden, impact on work and activity, and healthcare resource utilisation (HCRU) was examined at randomisation in patients enrolled in a clinical trial. Symptom burden was estimated based on self-reported health status measures. The Work Productivity and Activity Impairment: Specific Health Problem scale adapted to FM and a separate HCRU questionnaire were completed. The relationship between FM severity and burden was evaluated. RESULTS: The total population analysed comprised 193 patients; 71 (36.8%) had moderate FM and 119 (61.7%) severe FM. Patients had moderate pain, severe impairment in functioning due to FM, sleep disruption, mild anxiety, and mild depression. In the 7 days preceding randomisation, an average of 58.0% overall work impairment was reported, with 15.2% of working hours missed and 54.0% productivity while at work. In the 3 months preceding randomisation, on average, 5.0 visits per patient were made to healthcare professionals. Physical treatments were used by 34.7% and supplements by 31.6% of patients. Prescription and non-prescription medications, as well as professional services providing help with activities of daily living (ADL) that are impacted by FM, were used by >75% of patients. In addition, 50.4 hours of unpaid help was provided for ADL assistance. Total out-of-pocket expenditures were US$307.1, €410.4, or C$211.3, depending on location. FM burden worsened with increasing FM severity. CONCLUSIONS: This study demonstrates the significant burden of FM in patients with comorbid depression treated with an antidepressant.

Phase I study of oral CI-994 in combination with carboplatin and paclitaxel in the treatment of patients with advanced solid tumors.

PURPOSE: To determine maximum tolerated dose of CI-994, a novel oral histone deacetylase inhibitor, in combination with carboplatin and paclitaxel in patients with advanced solid tumors. PATIENTS AND METHODS: Patients with advanced solid tumors who had received two or fewer prior chemotherapy regimens were eligible for trial. Five cohorts of patients were treated with escalating doses (4-6 mg/m2) and alternative schedules (7 days or 14 days) of CI-994. Dose escalation of paclitaxel was performed to achieve tolerability of CI-994 with a paclitaxel dose of 225 mg/m2 when administered in combination with carboplatin. Pharmacokinetic assessment of CI-994 was performed by using liquid chromatography/mass spectrometry. Histone deacetylation inhibition was determined by Western blot analysis. RESULTS: A total of 30 patients (median age 58 years) were entered into five treatment cohorts. Maximum tolerated dose of CI-994 was determined to be 4 mg/m2 administered for 7 consecutive days following paclitaxel at a dose of 225 mg/m2 and carboplatin at an area under the curve (AUC) of 6 every 21 days. Neutropenia, thrombocytopenia, and grade 3 respiratory insufficiency limited further dose escalation of CI-994. Pharmacokinetics showed that CI-994 absorption and disposition were unaffected by carboplatin and paclitaxel coadministration. Association between histone H3 acetylation levels and disease response was suggested. A subset of patients with lymphocyte H3 acetylation levels at least 1.5-fold times baseline all achieved either a clinical response or stable disease. All evaluable patients with progressive disease (PD) had H3 acetylation levels <1.5-fold times baseline. Twenty-four of the 30 patients received greater than one cycle of treatment. Five of these patients achieved a partial response (3 nonsmall cell lung cancer, 1 colorectal cancer, and 1 unknown primary) and 2 patients achieved a complete response (esophageal and bladder cancer). CONCLUSION: The combination of CI-994 at a dose of 4 mg/m2 administered orally for 7 consecutive days can be safely coadministered with paclitaxel at a dose of 225 mg/m2 and carboplatin at an AUC of 6 on day 1 of a 21-day cycle. Evidence of antitumor activity is suggested and may correlate with histone modulation.