Cost-effectiveness of ravulizumab compared with eculizumab for the treatment of paroxysmal nocturnal hemoglobinuria in the Netherlands.

OBJECTIVES: The aim of this study was to evaluate the cost-effectiveness of ravulizumab compared with eculizumab for the treatment of adult patients with paroxysmal nocturnal hemoglobinuria (PNH) in the Netherlands. METHODS: A cost-effectiveness analysis was conducted based on a Markov cohort model simulating the course of patients with PNH with clinical symptom(s) indicative of high disease activity, or who are clinically stable after having been treated with eculizumab for at least the past six months. Costs, quality of life, and the incremental cost-effectiveness ratio (ICER) were estimated over a lifetime horizon from a Dutch societal perspective. Several additional analyses were performed, including a one-way sensitivity analysis, a probabilistic sensitivity analysis, and scenario analysis. RESULTS: When compared with eculizumab, ravulizumab saves €266,833 and 1.57 quality adjusted life years (QALYs) are gained, resulting in a dominant ICER. Drug costs account for the majority of the total costs in both intervention groups. Cost savings were driven by the difference in total treatment costs of ravulizumab compared with eculizumab caused by the reduced administration frequency, accounting for 98% of the total cost savings. The QALY gain with ravulizumab is largely attributable to the improved quality of life associated with less frequent infusions and BTH events. At a willingness-to-pay threshold of €20,000/QALY, there is a 76.6% probability that ravulizumab would be cost-effective. CONCLUSIONS: The cost reduction and QALY gain associated with the lower rates of BTH and less frequent administration make ravulizumab a cost-saving and clinically beneficial substitute for eculizumab for adults with PNH in the Netherlands.

Feasibility, toxicity, and preliminary results of weekly loco-regional hyperthermia and cisplatin in patients with previously irradiated recurrent cervical carcinoma or locally advanced bladder cancer.

PURPOSE: The biological rationale for combining locoregional hyperthermia (HT) with cisplatin (CDDP) is the potentiating effect of HT on CDDP uptake and cytotoxicity. Feasibility, toxicity, and preliminary results of a clinical trial of weekly loco-regional HT in combination with cisplatin are described in this article. METHODS AND MATERIALS: Patients with previously irradiated unresectable local recurrent cervical carcinoma or locally advanced bladder carcinoma were treated with weekly cycles of locoregional HT (70 MHz four antenna phased array system) for 1 h and CDDP 50 mg/m(2) IV for a maximum of 12 courses. RESULTS: Fourteen patients, 10 patients with recurrent cervical carcinoma and 4 with locally advanced bladder carcinoma, were entered in this study. A total of 100 cycles were given. Overall toxicity was acceptable; Grade 3 (WHO) toxicity (gastrointestinal, hematological, and neurotoxicity) was observed in 5 out of 14 patients. No Grade 4 toxicity was seen. Subcutaneously fatty necrosis due to HT occurred in 11% of the cycles, while two patients developed skin burns. Two out of 10 patients with recurrent cervical carcinoma were not evaluable for response. Four out of eight evaluable cervical carcinoma patients responded (two pathologic complete responses, one pathologic confirmed partial response, one partial response): response rate 50% (95% confidence interval 15.7-84.3%). Salvage surgery became possible in three out of four responding patients, whose tumors were previously considered unresectable. Two out of the four evaluable patients with locally advanced bladder carcinoma responded (two partial responses). CONCLUSIONS: Weekly loco-regional HT and CDDP 50 mg/m(2)/week for a maximum of 12 courses is feasible with an acceptable toxicity, which seems not to be enhanced by the addition of loco-regional HT. The encouraging preliminary results of this treatment schedule warrant further study, especially in patients with previously irradiated recurrent cervical carcinomas.

Phase II trial of weekly locoregional hyperthermia and cisplatin in patients with a previously irradiated recurrent carcinoma of the uterine cervix.

BACKGROUND: The biologic rationale for combining cisplatin with locoregional hyperthermia (HT) relates to the potentiating effect of HT on cisplatin cytotoxicity. METHODS: Patients with recurrent cervical carcinoma, who had a pelvic recurrence after radiotherapy, were treated with weekly cycles of locoregional HT (using the 70-megahertz, 4 antenna-phased array system for 1 hour and cisplatin, 50 mg/m2 intravenously [i.v.], for a maximum of 12 cycles.) RESULTS: Twenty-three patients were entered in this study. A total of 169 cycles were given. Responses were observed in 12 of 23 patients, a response rate of 52% (95% confidence interval, 31-73%). Salvage surgery became possible in 3 of 12 responding patients, whose tumors were previously considered unresectable. The median duration of response was 9.5+ months, the median overall survival was 8+ months, and the 1-year survival was 42%. No correlation was found between treatment outcome and clinical parameters such as age, weight, performance status, and histology. Thermal parameters such as T20, T50, and T90 were higher in responding patients, but were not significantly different from nonresponding patients. Overall toxicity was moderate. Subcutaneous fatty necrosis due to HT occurred in 10% of the cycles, whereas 2 patients developed skin burns. Squamous cell carcinoma antigen proved to be a valuable tool for the evaluation of response and detection of progression. CONCLUSIONS: Weekly locoregional HT and cisplatin, 50 mg/ m2 i.v., for a maximum of 12 cycles was effective treatment in patients with a previously irradiated recurrent carcinoma of the uterine cervix.