Abstract
Objective: In view of concerns about toxicity and deliverability of induction chemotherapy and its impact on subsequent chemoradiotherapy, a retrospective review was carried out with patients treated for locally advanced head and neck cancer (LAHNC) in a single centre between 2007-2017. Patients and Interventions: Patients with LAHNC and good performance status receiving induction chemotherapy with docetaxel, cisplatin and 5-fluorouracil (TPF) followed by chemoradiotherapy to 70Gy in 35 daily fractions with platinum-based chemotherapy. Main Outcome Measures: Overall and cause-specific survival, rates of locoregional recurrence or distant metastasis, treatment-related toxicity. Results: One hundred and eight patients with LAHNC were treated with 1-4 cycles of TPF (95 receiving two cycles) followed by chemoradiotherapy. The mean delivered dose intensity was 97.6% for all TPF cycles. Median interval from the start of the final cycle of TPF to the start of radiotherapy was 24 days, with 92/103 (89%) starting radiotherapy within 28 days. Median radiation treatment time was 47 days. The mean delivered dose intensity for chemotherapy delivered concurrently with radiotherapy was 97%. There were significantly fewer dose reductions in those receiving platinum/5FU combinations than platinum only regimes (P < 0.0001). For those receiving two cycles of TPF, 90% of patients completed the whole course of treatment within 14 weeks (median overall treatment time 13.1 weeks). There were four treatment-related deaths during induction chemotherapy and none during radiotherapy. Twenty-five developed locoregional failure and 13 distant metastases (both in eight). Actuarial overall survival was 60.7% at five years, with progression-free survival of 77.9% at two years and 74.1% at five years. For oropharynx cancers, overall survival was 70.4% and progression-free survival 80.8% at five years. Conclusion: Although significant toxicity from TPF was observed, with appropriate support, it is possible to complete treatment without undue compromise of subsequent treatment.
Highlights
In the search for more effective treatments for locally advanced head and neck cancer (LAHNC), there has been a steady increase in treatment intensity
Induction chemotherapy reduces the risk of distant metastases, given their relatively low incidence in LAHNC, survival is mostly determined by locoregional control [6, 7]
Patients with LAHNC were considered for TPF induction chemotherapy if, in general, they were of excellent performance status (WHO PS0) and age under 70, with tumors staged as T4 and/or N3, or of sufficient tumor bulk to warrant induction chemotherapy or where this might offer a greater possibility of organ preservation
Summary
In the search for more effective treatments for locally advanced head and neck cancer (LAHNC), there has been a steady increase in treatment intensity. The use of induction chemotherapy can produce higher response rates but translating that into improvements in survival has proven more difficult [1]. A meta-analysis of randomized trials conducted between 1965 and 2000 showed a small but not statistically significant survival benefit (2.3% at 5 years) from the addition of induction chemotherapy to locoregional treatment with radiotherapy or Induction TPF in Locally Advanced H&N Cancer chemoradiotherapy (LRT) [2]. In a meta-analysis of five trials (1772 patients), TPF induction produced a 7.4% improvement in overall survival at five years [3]. A subsequent meta-analysis of six trials (1280 patients) of LRT with or without TPF induction found, somewhat paradoxically, no survival advantage with TPF induction, significant improvement in overall and progression-free survival was seen in non-oropharyngeal cancers [6]. Induction chemotherapy reduces the risk of distant metastases, given their relatively low incidence in LAHNC, survival is mostly determined by locoregional control [6, 7]
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