title: Dihydropyrimidine dehydrogenase mutation in neoadjuvant chemotherapy in head and neck cancers: Myth or reality?
abstract: OBJECTIVE
  The docetaxel, 5-fluorouracil (5-FU), and cisplatin (TPF) regimen in India is associated with high percentages of Grade 3-4 toxicity. This analysis was planned to evaluate the incidence of dihydropyrimidine dehydrogenase (DPD) mutation in patients with severe gastrointestinal toxicity, to assess whether the mutation could be predicted by a set of clinical criteria and whether it has any impact on postneoadjuvant chemotherapy response.
  
  
  METHODS
  All consecutive patients who received TPF regimen in head and neck cancers between January 2015 and April 2015 were selected. Patients who had predefined set of toxicities in Cycle 1 were selected for DPD mutation testing. Depending on the results, C2 doses were modified. Postcompletion of two cycles, patients underwent radiological response assessment. Descriptive statistics has been performed. The normally distributed continuous variables were compared by unpaired Student'st-test, whereas variables which were not normally distributed by Wilcoxon sum rank test. For noncontinuous variables, comparison was performed by Fisher's exact test.
  
  
  RESULTS
  Out of 34 patients, who received TPF, 12 were selected for DPD testing, and 11 (32.4%, 95% confidence interval [95% CI]: 19.1-49.3%) had DPD mutation. The predictive accuracy of the criteria for the tested DPD mutations was 81.3% (95% CI: 62.1-100%). Of the 11 DPD mutation positive patients, except for one patient, all others received the second cycle of TPF. The dose adjustments done in 5-FU were 50% dose reduction in 9 patients and no dose reduction in one patient. The response rate in DPD mutated patients was 27.3% (3/11) and that in DPD nonmutated/nontested was 39.1% (9/23) (P= 0.70).
  
  
  CONCLUSIONS
  In this small study, it seems that the incidence of DPD mutation is more common in Indian then it's in the Caucasian population. Clinical toxicity criteria can accurately predict for DPD mutation. Postdose adjustments of 5-FU from C2 onward, TPF can safely be delivered in the majority of patients with DPD heterozygous mutations without decrement in efficacy.
authors.affiliation: Department of Medical Oncology, Tata Memorial Hospital, Mumbai, Maharashtra, India.
authors.forename: Vijay M
authors.initials: VM
authors.lastname: Patil
authors.affiliation: Department of Medical Oncology, Tata Memorial Hospital, Mumbai, Maharashtra, India.
authors.forename: Vanita
authors.initials: V
authors.lastname: Noronha
authors.affiliation: Department of Medical Oncology, Tata Memorial Hospital, Mumbai, Maharashtra, India.
authors.forename: Amit
authors.initials: A
authors.lastname: Joshi
authors.affiliation: Department of Medical Oncology, Tata Memorial Hospital, Mumbai, Maharashtra, India.
authors.forename: Saurabh
authors.initials: S
authors.lastname: Zanwar
authors.affiliation: Department of Medical Oncology, Tata Memorial Hospital, Mumbai, Maharashtra, India.
authors.forename: Anant
authors.initials: A
authors.lastname: Ramaswamy
authors.affiliation: Department of Radiodiagnosis, Tata Memorial Hospital, Mumbai, Maharashtra, India.
authors.forename: Supreeta
authors.initials: S
authors.lastname: Arya
authors.affiliation: Department of Radiodiagnosis, Tata Memorial Hospital, Mumbai, Maharashtra, India.
authors.forename: Abhishek
authors.initials: A
authors.lastname: Mahajan
authors.affiliation: Division of Clinical Research and Biostatistics, Malabar Cancer Centre, Kannur, Kerala, India.
authors.forename: Atanu
authors.initials: A
authors.lastname: Bhattacharjee
authors.affiliation: Department of Medical Oncology, Tata Memorial Hospital, Mumbai, Maharashtra, India.
authors.forename: Kumar
authors.initials: K
authors.lastname: Prabhash
keywords: 5-fluorouracil; dihydropyrimidine dehydrogenase mutation; head and neck cancers; neoadjuvant chemotherapy; toxicity