Phase I trial of the novel taxane BMS-184476 administered in combination with carboplatin every 21 days.

The aim of the study was to determine the maximum-tolerated dose and dose-limiting toxicities for BMS-184476, in combination with carboplatin, in patients with advanced solid tumours and to describe any preliminary antitumour activity associated with this regimen. Patients received combination therapy with BMS-184476 given intravenously over 1 h followed by carboplatin administered over 30 min on day 1 of a 21-day cycle. In all, 28 patients received 146 cycles of BMS-184476 and carboplatin. Patients were enrolled at four dose levels: BMS-184476 (mg m(-2))/carboplatin (mg min ml(-1)): 40/5, 50/5, 50/6 and 60/6. Dose-limiting toxicity at 60/6 was neutropenia. Among 27 evaluable patients, 11 demonstrated stable disease for a median of 8.5 cycles. In 22 patients, the pharmacokinetics of BMS-184476 appeared independent of dose of BMS-184476. The mean+/-s.e.m. values for clearance (Cl), volume of distribution at steady state and apparent terminal half-life of BMS-184476 in the four dose groups during cycle 1 were 192+/-25 ml min m(-2), 377+/-69 l m(-2) and 33.7+/-5.9 h, respectively. An increase in the dose of carboplatin from 5 to 6 mg min ml(-1) may have decreased Cl of BMS-184476. BMS-184476 in combination with carboplatin was well tolerated at a dose of 50/6 and shows evidence of antitumour activity in a pretreated population.

The costs of children with sickle cell anemia: preparing for managed care.

PURPOSE: To anticipate the clinical challenges and financial risks facing physicians and managed care organizations who care for children with chronic illnesses, such as sickle cell anemia (SCA), under capitated managed care arrangements. PATIENTS AND METHODS: A cross-sectional study based on claims data from the Washington State Medicaid Program (WSMP) and the Federal Employees Health Benefits Program (FEP). Expenditure patterns were compared for children 18 years of age or younger for whom a claim with a diagnosis of SCA was submitted and paid in the State of Washington during fiscal year 1993 (FY1993) or by the FEP during FY1992 to expenditure patterns for all children. RESULTS: Children with SCA had mean expenditures 8.8 times the mean expenditures for all children in WSMP. There was wide variation in the annual expenditures among children with SCA; the most expensive 10% of children accounted for 56% of total expenditures. Ninety-seven percent of the expenditures were concentrated in four broad categories: 72% for inpatient care, 11% for outpatient care, 11% for physician payments, and 3% for prescription drugs. Examination of expenditure and utilization patterns for children with sickle cell anemia enrolled in the FEP yielded similar results. CONCLUSIONS: Unless managed care organizations and capitated pediatricians receive payment rates that reflect the higher expected expenditures of caring for these children, access to and quality of care may suffer. Analyses of practice guidelines and utilization patterns suggest that newborn screening, regular access to specialty facilities, and comprehensive education programs are critical areas that are vulnerable to reductions under capitation.

Capitation payment rates and implications for the general pediatrician.

Many pediatricians are beginning to sign capitated contracts that require them to provide services to children on an annual basis for a predetermined price. However, not all children have the same expected cost. Children with chronic illnesses, for example, are much more likely to incur higher costs than their healthy peers. This article summarizes the recent literature on payment systems that have been developed to establish capitated rates. It also summarizes other methods for reducing the risk that pediatricians face when they accept capitated payments. Finally, it discusses physicians'-perceptions of how capitation affects their practice.