Abstract Purpose: Evaluation the tolerability, toxicity profile, and the outcome of treating locally advanced squamous cell carcinoma of the head and neck with altered cisplatin dose regimen concomitantly with radiotherapy. Materials and methods: This study was based on a retrospective analysis of 48 patients treated with Concomitant Chemoradiotherapy (CCRT) using fractionated cisplatin doses of 20 mg/m2 from days 1 to 5 in the first and fifth weeks of radiotherapy. The follow-up was performed during the treatment and four weeks after the end of radiation in cooperation with the Otorhinolaryngology department. Results: 45 patients (93.8%) out all 48 completed the whole treatment protocol. The incidence of grade II or acute toxicities were: mucositis 64.6%, dysphagia 50% and grade II or III haematological events 14.6%. The late toxicities included: Xerostomia 33.3% dysphagia 29.2% trismus 14.6% deafness 14.6% dysgeusia 16.7%. The median follow-up time was 3.7 years after the treatment. 15 patients (31.3%) experienced recurrences and the 2- year disease free survival (DFS) was 70.8%. The 2-year overall survival (OS) was 85.4% among all patients. Conclusion: The studied altered cisplatin protocol shows higher compliance and tolerability in comparison to the standard high cisplatin schedule and similar to the weekly one. Regarding the OS and DFS, the study shows comparable results with other cisplatin regimens. However, further phase III randomized multicentre studies are required to determine the most effective and least toxic cisplatin regimen in head and neck cancer patients treated with CCRT.

The superiority of Concomitant Chemoradiotherapy (CCRT) over Radiotherapy (RT) alone in the management of locally advanced squamous cell carcinoma of the head and neck is has previously been demonstrated through several randomized trials. It is now considered the standard treatment of locally advanced inoperable head and neck cancers; it is also employed as an adjuvant treatment in high risk patients, improving the local control rate (LCR) by 10% and the overall survival (OS) by 6% compared to RT alone. Various chemotherapeutic agents have been tested in the last six decades with an obvious superiority of platinum based chemotherapy in head and neck cancers. However, whether cisplatin is more effective alone or combined with other agents has not yet been determined. Multiple cisplatin regimens with different dosages and schedules have been studied in order to identify the most effective and least toxic regimen with indefinitely results. The standard high dose cisplatin regimen of 100 mg/m² every 3 weeks (on days 1, 22, and 42 of treatment) is usually accompanied by several acute toxicities which may interrupt the treatment plan, which could lead to reduce the previously prescribed total cisplatin dose. That’s why arises the need of different cisplatin schedule having the same effect and better toxicity profile. One of the most widely used alternatives is a weekly low dose cisplatin schedule (30-50 mg/m²), which was tested in several studies showing higher compliance with an acceptable toxicity profile in comparison to the high dose regimen. Regarding the treatment outcome demonstrates the meta-analysis study by Jacinto et al. that there is no superiority of the weekly protocol over the triweekly standard regimen. Interestingly showed the study that there is no difference in acute toxicity between the two schedules. Several other studies demonstrate the superiority of the high dose cisplatin regimen over the weekly low dose regimen in terms of OS and DFS. This retrospective study was conducted at SRH Wald- Klinikum Gera hospital aiming to evaluate the compliance, toxicity as well as the outcome and efficacy of treating 48 patients in the period from March 2010 to August 2015 and comparing the results with similar, previously conducted studies. The patients were selected with the following inclusion criteria: histopathologically diagnosed squamous cell carcinoma of the oral cavity, oropharynx, hypopharynx or larynx; stage III or IV according to AJCC 7^th Edition; normal haematological, renal and liver functions; performance status Eastern Cooperative Oncology Group (ECOG) ≥ 2; no history of prior chemotherapy or radiotherapy.

The CCRT is the standard treatment of locally advanced head and neck carcinoma in both definitive inoperable sitting and in case of high rick postoperative situations. Cisplatin is one of the most widely accepted chemotherapeutic agents in the CCRT, either alone or in combination with other agents aiming to reduce the toxicity and overcoming the resistance. Cisplatin is cleared majorly through the kidney and accumulated in the proximal renal tubules causing nephrotoxicity other known toxicities are ototoxicity and haematological toxicities. The half-life of cisplatin is 20-30 mints following bolus administration. Platinum and not cisplatin itself remain present in the tissues for as long as 180 days after the last administration. The concentration of cisplatin in tumour is more than in other tissues. This study showed that a fractioned cisplatin program (20 mg/m² ) over 5 days in the first and fifth radiotherapy weeks achieve higher compliance and tolerability in comparison to the standard highly cisplatin regimen (100 mg/m² every 3 weeks) and similar toxicity profile to the weekly cisplatin schedule ( 30-50 mg/m² once weekly). In comparison to other cisplatin regimen in the previously conducted studies were the OS and DFS in our study similar in patients treated with definitive intent and higher in those treated adjuvant. Further prospective randomized multicenter studies are required to determine the most effective and least toxic cisplatin regimen in the head and cancer patients treated with concomitant chemo radiation.

With Regards,
Joseph Kent
Journal Manager
Journal of Brain Behaviour & Cognitive Sciences