Comparison of response and acute toxicities of concurrent chemoradiation with weekly cisplatin vs. paclitaxel/carboplatin in locally advanced squamous cell carcinoma of head & neck: Protocol of a short-term phase III trial

Concurrent chemoradiation therapy (CCRT) has become the treatment of choice for locally advanced squamous cell carcinoma of head & neck (SCCHN). Multiple chemoradiation treatment paradigms are existent, but unfortunately the optimum timing, dosing and choice of systemic agents are controversial. Even though the current most widely accepted standard chemotherapy for radiation sensitization remains cisplatin, the toxicities are significant. Carboplatin possesses radiationsensitizing properties as a result of its ability for repairing sublethal damage, binding thiols and inducing chromosomal aberrations. Compared to cisplatin, it is less nephrotoxic, neurotoxic and ototoxic. Paclitaxel is also a potent radiosensitizer, as demonstrated in preclinical and clinical trials, due to its effect of inducing cell cycle arrest in G2/M phase. The combining of carboplatin and paclitaxel with radiation has demonstrated promising clinical activity in respect of efficacy and improved tolerability against newly diagnosed, recurrent and metastatic SCCHN. This study intends to explore the advantage of multiagent CCRT with taxane over single agent cisplatin for patients with locally advanced, non-metastatic SCCHN. Patients with stage-III & IVA/B SCCHN will be randomly enrolled to receive following treatments: CDDP arm-Cisplatin (30mg/m2) weekly plus radiotherapy (RT) (66-70 Gy, 1.8-2 Gy/ fraction); PC arm-weekly paclitaxel (40mg/m2) and carboplatin (AUC-2) plus RT (66-70 Gy, 1.8-2 Gy/ fraction). Patients will be followed-up weekly and six weeks after completion of treatment, and treatment response will be evaluated with RECIST criteria. Toxicities will be assessed by RTOG Acute Radiation Morbidity Criteria. Chi-squared test, Fisher’s exact test and t-test will be employed to compare between two treatment arms. Ethics and dissemination: The study is registered at German Clinical Trials Register (DRKS00012877) and “National Institute of Cancer Research & Hospital Ethics Committee”, Bangladesh (Ethical Clearance Certificate Reference: NICRH/Ethics/2015/185). Results will be disseminated through peer-reviewed international journals and major international conferences. Trial registration number: DRKS00012877. http://www.drks. de/DRKS00012877 *Correspondence to: Md Shuayb, Square Oncology & Radiotherapy Centre, Square Hospitals Ltd., 18/F, West Panthapath, Dhaka 1205, Bangladesh, Tel: +8801553139179; E-mail: m.shuayb@yahoo.co.uk; drshuayb@squarehospital.com Received: April 27, 2018; Accepted: May 23, 2018; Published: May 28, 2018 Abbreviations: AUC: Area Under the Curve; CCRT: Concurrent Chemoradiation Therapy; CT: Computed Tomography; ECOG: Eastern Cooperative Oncology Group; Gy: Gray; LRC: Loco Regional Control; OS: Overall Survival; PFS: Progression Free Survival; RECIST: Response Evaluation Criteria for Solid Tumor; RT: Radiotherapy; RTOG: Radiation Therapy Oncology Group; SCCHN: Squamous Cell Carcinoma of Head and Neck; SPSS: Statistical Package for Social Sciences Article Summary Article focus 1. Our hypothesis is that taxane containing regimen is superior to cisplatin only regimen in combination with radiation therapy for locally advanced SCCHN.