Petr Szturz1, Kristien Wouters2, Naomi Kiyota3, Makoto Tahara4, Kumar Prabhash5, Vanita Noronha5, David Adelstein6, Jan B Vermorken7. 1. Department of Internal Medicine, Hematology, and Oncology, University Hospital Brno, Brno, Czech Republic; School of Medicine, Masaryk University, Brno, Czech Republic. Electronic address: szturz@gmail.com. 2. Scientific Coordination and Biostatistics, Antwerp University Hospital, Edegem, Belgium; Faculty of Medicine and Health Sciences, University of Antwerp, Antwerp, Belgium. 3. Kobe University Hospital Cancer Center, Kobe, Hyogo, Japan. 4. Department of Head and Neck Medical Oncology, National Cancer Center Hospital East, Chiba, Japan. 5. Department of Medical Oncology, Tata Memorial Hospital, Mumbai, Maharashtra, India. 6. Department of Hematology and Medical Oncology, Taussig Cancer Institute, Cleveland Clinic, Cleveland, OH, United States. 7. Faculty of Medicine and Health Sciences, University of Antwerp, Antwerp, Belgium; Department of Medical Oncology, Antwerp University Hospital, Edegem, Belgium.
Abstract
OBJECTIVES: Altered fractionation radiotherapy and concomitant chemoradiotherapy represent commonly used intensification strategies in the management of locally advanced squamous cell carcinoma of the head and neck (LA-SCCHN). This meta-analysis compares compliance, safety, and efficacy between two single-agent cisplatin schedules given concurrently with altered fractionation radiotherapy. METHODS: We systematically searched for prospective trials of patients with LA-SCCHN who received post-operative or definitive altered fractionation concurrent chemoradiotherapy. High-dose cisplatin once every three to four weeks (100 mg/m2, 2 doses) was compared with a weekly low-dose protocol (≤50 mg/m2, ≥4 doses). The primary outcome was overall survival. The secondary endpoints comprised treatment adherence, acute and late toxicities, and objective response rate. RESULTS: Twelve studies with 1373 patients treated with definitive chemoradiotherapy were included. Compared to the weekly low-dose cisplatin regimen, the three- to four-weekly high-dose cisplatin regimen improved overall survival (p=.0185), was more compliant with respect to receiving all planned cycles of cisplatin (71% versus 95%, p=.0353), and demonstrated less complications in terms of severe (grade 3-4) acute mucositis and/or stomatitis (75% versus 40%, p=.0202) and constipation (8% versus 1%, p=.0066), toxic deaths (4%, versus 1%, p=.0168), 30-day mortality (8% versus 3%, p=.0154), and severe late subcutaneous fibrosis (21% versus 2%, p<.0001). Overall and complete response rates were similar between both chemotherapy schedules. CONCLUSION: In chemoradiotherapy incorporating altered fractionation, two cycles of high-dose cisplatin with a three to four week interval are superior to weekly low-dose schedules. Further studies should identify those who might derive the greatest benefit from this intensified approach.
OBJECTIVES: Altered fractionation radiotherapy and concomitant chemoradiotherapy represent commonly used intensification strategies in the management of locally advanced squamous cell carcinoma of the head and neck (LA-SCCHN). This meta-analysis compares compliance, safety, and efficacy between two single-agent cisplatin schedules given concurrently with altered fractionation radiotherapy. METHODS: We systematically searched for prospective trials of patients with LA-SCCHN who received post-operative or definitive altered fractionation concurrent chemoradiotherapy. High-dose cisplatin once every three to four weeks (100 mg/m2, 2 doses) was compared with a weekly low-dose protocol (≤50 mg/m2, ≥4 doses). The primary outcome was overall survival. The secondary endpoints comprised treatment adherence, acute and late toxicities, and objective response rate. RESULTS: Twelve studies with 1373 patients treated with definitive chemoradiotherapy were included. Compared to the weekly low-dose cisplatin regimen, the three- to four-weekly high-dose cisplatin regimen improved overall survival (p=.0185), was more compliant with respect to receiving all planned cycles of cisplatin (71% versus 95%, p=.0353), and demonstrated less complications in terms of severe (grade 3-4) acute mucositis and/or stomatitis (75% versus 40%, p=.0202) and constipation (8% versus 1%, p=.0066), toxic deaths (4%, versus 1%, p=.0168), 30-day mortality (8% versus 3%, p=.0154), and severe late subcutaneous fibrosis (21% versus 2%, p<.0001). Overall and complete response rates were similar between both chemotherapy schedules. CONCLUSION: In chemoradiotherapy incorporating altered fractionation, two cycles of high-dose cisplatin with a three to four week interval are superior to weekly low-dose schedules. Further studies should identify those who might derive the greatest benefit from this intensified approach.
Authors: Brandon C Leonard; Eliot D Lee; Neil E Bhola; Hua Li; Kristian K Sogaard; Christopher J Bakkenist; Jennifer R Grandis; Daniel E Johnson Journal: Oral Oncol Date: 2019-06-06 Impact factor: 5.337
Authors: Petr Szturz; Kristien Wouters; Naomi Kiyota; Makoto Tahara; Kumar Prabhash; Vanita Noronha; David Adelstein; Dirk Van Gestel; Jan B Vermorken Journal: Front Oncol Date: 2019-02-21 Impact factor: 6.244
Authors: Marco Siano; Pavel Dulguerov; Martina A Broglie; Guido Henke; Paul Martin Putora; Christian Simon; Daniel Zwahlen; Gerhard F Huber; Giorgio Ballerini; Lorenza Beffa; Roland Giger; Sacha Rothschild; Sandro V Negri; Olgun Elicin Journal: Front Oncol Date: 2019-10-24 Impact factor: 6.244