1057 - Pharmacokinetic and pharmacodynamic analysis of 5-fluorouracil in Chinese head and neck cancer (HNC) patients

Date 28 September 2012
Event ESMO Congress 2012
Session Publication Only
Topics Anticancer Agents
Head and Neck Cancers
Biological Therapy
Presenter Liping Zhao
Authors L. Zhao1, W. Liu2, X. Guo2, C. Zhao2, Y. Huang2, F. Xu2, L. Zhang2
  • 1Medical Oncology Dept., Cancer Center of Sun Yat-Sen University, 510060 - Guangzhou/CN
  • 2Medical Oncology, Sun Yat-Sen University Cancer Center, 510060 - Guangzhou/CN



Pharmacokinetic (PK) variability of 5-fluorouracil (5-FU) has been demonstrated for +30 years and a significant link between exposure and therapeutic response has been identified. A maximum tolerated exposure (MTE) from the area under curve (AUC) has been characterized for various regimens and therapeutic dose management (TDM) has been used to optimize dosing.


The objective of this study was to characterize the PK variability of 5-FU in the Chinese HNC population and examine the relationship between AUC, toxicity and efficacy. The 5-FU MTE in this population was compared with MTE identified for European HNC patients.


89 treatment naïve patients with HNC were administered cisplatin (80mg/m2, d1) and 5-FU (4g/m2, 120h IV). Blood samples were collected at steady state after the first 18h of 5-FU infusion. Plasma was analyzed by a 5-FU immunoassay and AUC was calculated. Relationship between 5-FU AUC and 5-FU related toxicities was examined. Preliminary efficacy results were evaluated for 5-FU related toxicity.


The patient 5-FU AUC values varied widely: from 15 to 103 mg · h/L. 33% of patients were within the target range of 25-35 mg· h/L; 18% were below and 49% were above . Toxicity was recorded for 89 patients. Among the 44 patients with AUC above the target range, severe mucositis or mylesupression was experienced by 32 patients. By comparison, among the 45 patients within or below target range, only 3 experienced severe toxicities. ROC analysis for 5-FU AUC and severe mucositis identified a cut-point of 36 mg· h/L (p < 0.0001). These results are listed in the table below.

Incidence of severe mucositis and myelosuppression with 5-FU AUC
AUC ≤35 mghr/L >35 mghr/L
Grade 3 3% 36%
Grade 0 - 2 47% 13%


Results of this study demonstrate wide PK-variability of 5-FU exposure and a significant relationship between severe toxicity and AUC in HNC cancer patients. The study confirms that the MTE in this population is similar to a European HNC population treated with cisplatin/5-FU. TDM using the target range of 25-35 mg· h/L may have benefit in lowering toxicity in HNC patients.


All authors have declared no conflicts of interest.