Abstract
Introduction: Docetaxel, Cisplatin and 5-Fluorouracil (DPF) became the standard induction chemotherapy in advanced Head and Neck Cancer (HNC) but associated with high toxicity rate. Several studies reported higher response rates with better tolerability when chemotherapy dose is calculated based on Pharmacokinetics (PK) versus conventional Body Surface Area (BSA). Patients and Methods: Thirty nine patients with stage III and IV HNC who received induction DPF were included in the study. Dose of cycle 1 was BSA-based then Docetaxel and 5-FU doses were PK-adjusted starting from cycle 2 whereas Cisplatin dose was BSA-based throughout the study. Results: After median follow up period of 14 months the median overall survival (OS) and progression free survival (PFS) were 15.1 and 10.6 months respectively. Twenty nine patients were available for response assessment. Seven patients (24.1%) achieved complete response while partial response encountered in 19 patients (65.5%) with and Overall response rate of 89.6%. Both treatment related side effects and mortality significantly decreased after the application of PK dose adjustments (p-value 0.007 and 0.01 respectively). Conclusion: PK-guided dose adjustments of 5-FU and Docetaxel in DPF regimen can significantly decrease the treatment related side effects and mortality without compromising the tumor response rate. A randomized clinical trial is needed to compare the PK-guided dose adjustment with the standard BSA based protocol.
Highlights
Head and Neck Cancers (HNCs) are heterogeneous group of cancers
We proposed this study aiming to investigate the application of PKguided 5-FU and Docetaxe l dosing and to evaluate its effect on treatment outcome and toxicity profile
Docetaxe l and 5-FU continuous intravenous infusion (CIVI) doses were adjusted starting from the second cycle and onwards using a PK-guided dose-adjustment algorithm based on plasma concentration results of the preceding cycle that was expressed as area under the concentration-time curve (AUC) dose /h/L (Tabl e 1)
Summary
Head and Neck Cancers (HNCs) are heterogeneous group of cancers. That may differ in location, pathogenesis, tumor biology, treatment, prognosis and effect on quality of life [1]. The BSA-based dose for any drug is recommended by the manufacturer according to the maximum tolerated dose (MTD) achieved during phase I studies. BSA-based dosing is associated with drug plasma leve l variability up to 30-fold. Former studies reported that 20% - 30% of patients treated with BSA-based 5-FU dosing have drug exposure levels within a previously established therapeutic range [area under the concentration-time curve (AUC) 20 - 25 mg/h/L], whereas approximately 40% - 60% and 10% - 20% are under and over this therapeutic AUC threshold respectively. There is lack of prospective studies that clarify the concept of modifying the Docetaxel dose based on drug PKs to achieve the target AUC. We proposed this study aiming to investigate the application of PKguided 5-FU and Docetaxe l dosing and to evaluate its effect on treatment outcome and toxicity profile
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