Pharmacoeconomic study in head and neck cancer patients: Impact of prospective DPD deficiency screening with 5-fluorouracil (5-FU) dose tailoring on toxicities-related costs

Abstract

6515 Background: Dihydropyrimidine dehydrogenase (DPD) plays a pivotal role in the detoxification of 5-FU. We studied the impact of screening DPD impairment in head and neck cancer (HNC) patients, both on reduction of drug-related toxicities and as a pharmacoeconomic endpoint. Methods: A total of 148 consecutive patients with HNC treated with 5-FU+platinum were monitored. Seventy-four patients (Arm A - before 2006) were treated with standard dosage, whereas 74 other patients (Arm B - after 2006) had their DPD status phenotypically evaluated prior to receiving 5-FU, with subsequent dose reduction if DPD deficiency were suspected. Severe toxicities and response were compared. Additionally, direct and indirect costs required to manage the treatment-related toxicities and to establish DPD status were calculated. Results: Sepsis was observed in 16.2% of patients treated with standard dosage. In Arm B, DPD deficiency was suspected in 35% of the patients and 5-FU dosage was subsequently reduced. Consequently, only 1.8% of them experienced sepsis. Of note, response rates were comparable between Arm A and B (62 vs 61%, p>0.05), thus demonstrating that 5-FU dose tailoring did not negatively impact on treatment efficacy, while reducing the occurrence of severe toxicities. Managing toxicities required an average 23-days of extra-hospitalization (4–96 days), including an average 1.6-day stay in ICU. No patients from Arm B had to stay in ICU. Drugs required for managing toxicities cost an average of $339 per patient (Arm A) and was reduced down to $38 per patient (Arm B). Similarly, mean extra-hospitalization cost was $5,940/patient in Arm A and $245/patient in Arm B. Testing DPD cost $49/patient in Arm B. Conclusions: Developing an adaptative dosing strategy based upon DPD status evaluation led to a dramatic reduction of the incidence of 5-FU-related severe toxicities, while maintaining optimal efficacy. Subsequently, extra-cost (medication + hospitalization costs) required to manage the toxicities fell down from $6,279 to $294/patient. Overall, this study advocates that systematic screening for DPD deficiency could be cost-efficient in the setting of 5-FU-based chemotherapies, with a reduction of 95% of the extra-costs. No significant financial relationships to disclose.