Abstract

BackgroundThe rate of toxic deaths related to induction chemotherapy in the treatment of locally advanced head and neck cancers is unacceptable and calls into question this therapeutic strategy, which is however highly effective in terms of rate and speed of response. The purpose of the study was to investigate predictive factors of toxicity of induction chemotherapy with docetaxel, cisplatin, and 5-fluorouracil (TPF) in locally advanced head and neck cancers (LAHNC).MethodsBetween June 2009 and December 2017, 113 patients treated consecutively with TPF were included retrospectively. Patients were receiving induction chemotherapy for either an inoperable cancer or laryngeal preservation. For inoperable cancer, induction chemotherapy was proposed to patients presenting either a large tumor with strong symptoms (dyspnea, dysphagia, pain) or a tumor with rapid progression. Risk factors were chosen among the initial patient and tumour characteristics and chemotherapy modalities.ResultsEighty-nine patients (79%) were male; the median age was 58 years [32–71]. Sixty-nine (61%) patients were treated for inoperable cancer and 44 (39%) for laryngeal preservation. 45% had stage IVa cancer, 28% stage III and 25% stage IVb. Sixty percent of patients had a partial response after TPF, 22% had a complete response, 12% were stable, 5% were progressing, and 1% had a discordant response. Thirty-four patients (30%) received enteral feeding during induction chemotherapy with TPF. The possibility of oral feeding without a tube was predictive of a better response (p = 0.003). Seven (6%) patients died during TPF. There was an increased risk of death with preexisting liver dysfunction (liver dysmorphia on imaging or decrease prothrombin rate) (p = 0.032). There was an increased risk of grade ≥ 3 infection if an enteral feeding occurred during the period of induction chemotherapy (p = 0.03).ConclusionsTPF induction chemotherapy had an 82% objective response rate with 6% toxic deaths. Nutritional status and the presence of hepatic dysfunction are significant risk factors to be taken into account in therapeutic decisions.

Highlights

  • The rate of toxic deaths related to induction chemotherapy in the treatment of locally advanced head and neck cancers is unacceptable and calls into question this therapeutic strategy, which is highly effective in terms of rate and speed of response

  • The main aim of this study was to identify predictive factors of toxicity of docetaxel, cisplatin, and 5fluorouracil (TPF) in locally advanced head and neck cancers (LAHNC), in order to better select patients likely to benefit from this treatment

  • The median age was 58 years [32– 71]. 96% of patients had a World Health Organization (WHO) performance status of 0 or 1. 70% of patients had a history of alcohol and tobacco intoxication

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Summary

Introduction

The rate of toxic deaths related to induction chemotherapy in the treatment of locally advanced head and neck cancers is unacceptable and calls into question this therapeutic strategy, which is highly effective in terms of rate and speed of response. To improve cure rates and functional outcomes, chemotherapy has been integrated into various strategies (concurrent radiochemotherapy, induction chemotherapy and a combination of both) [6,7,8,9,10,11,12,13] These strategies have been applied in patients with nonoperable cancers [6,7,8,9,10,11, 14] and in patients with resectable disease who are candidates for organ preservation [9, 12, 13, 15,16,17]. TPF induction chemotherapy, already used in laryngeal preservation strategies, has been extended to all inoperable LAHNSCC with large tumour (T3 - T4) or lymph node extension (N2c - N3) with high risk of micro-metastases, without any formal proof of its superiority or non-inferiority compared to the standard treatment of concomitant radiochemotherapy

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