Low-Dose vs. High-Dose Cisplatin: Lessons Learned From 59 Chemoradiotherapy Trials in Head and Neck Cancer
In locally advanced squamous cell carcinomas of the head and neck (LA-SCCHN), concurrent chemoradiotherapy is an integral part of multimodality management both in the adjuvant and in the definitive settings. Although de-intensification strategies have been propelled to the forefront of clinical rese...
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Frontiers Media S.A.
2019-02-01
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| Series: | Frontiers in Oncology |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fonc.2019.00086/full |
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| author | Petr Szturz Kristien Wouters Kristien Wouters Naomi Kiyota Makoto Tahara Kumar Prabhash Vanita Noronha David Adelstein Dirk Van Gestel Jan B. Vermorken Jan B. Vermorken |
| author_facet | Petr Szturz Kristien Wouters Kristien Wouters Naomi Kiyota Makoto Tahara Kumar Prabhash Vanita Noronha David Adelstein Dirk Van Gestel Jan B. Vermorken Jan B. Vermorken |
| author_sort | Petr Szturz |
| collection | DOAJ |
| description | In locally advanced squamous cell carcinomas of the head and neck (LA-SCCHN), concurrent chemoradiotherapy is an integral part of multimodality management both in the adjuvant and in the definitive settings. Although de-intensification strategies have been propelled to the forefront of clinical research in human papillomavirus (HPV) positive oropharyngeal cancer, three cycles of 100 mg/m2 cisplatin given every 3 weeks concurrently with conventionally fractionated external beam radiotherapy represent a cost-effective and globally accessible treatment option for the majority of LA-SCCHN cases. Based on four large randomized trials, this regimen has become the non-surgical standard of care for cisplatin-eligible patients. Nevertheless, the outcomes in terms of efficacy, toxicity, and compliance have been rather disappointing. Therefore, there is an unmet need to find a better alternative. With limited support from randomized trials, weekly low-dose cisplatin regimens have replaced the standard high-dose schedule at some institutions. Four prospective trials exploring radiotherapy with and without weekly low-dose cisplatin have been published. Two of them were conducted in the 1980s, one of which had a negative outcome, the third study provided insufficient information on toxicity, and the fourth trial had to be prematurely terminated due to poor accrual. Moreover, the findings of two phase III trials comparing the two concurrent cisplatin regimens favored the high-dose protocol. We performed a composite meta-analysis of 59 prospective trials enrolling a total of 5,582 patients. The primary endpoint was overall survival. Reflecting different radiotherapy fractionation schemes and treatment intents, three meta-analyses were carried out, one for postoperative conventional chemoradiotherapy, one for definitive conventional chemoradiotherapy, and one for definitive altered fractionation chemoradiotherapy. In the former two settings, both high- and low-dose regimens yielded similar survival outcomes, thus, the primary objective was not met. When given concurrently with altered fractionation radiotherapy, patients treated with high-dose cisplatin had significantly longer overall survival than those who received low-dose cisplatin. In this article we provide a synthetic view of the results, discuss the issue of cumulative dose, compare two vs. three cycles of high-dose cisplatin, and present our three-step recommendations for use of the current standard of care, high-dose cisplatin, in clinical practice. |
| first_indexed | 2024-12-21T02:29:03Z |
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| id | doaj.art-93af7f93fd554c18b48c977f8ad59a0f |
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| language | English |
| last_indexed | 2024-12-21T02:29:03Z |
| publishDate | 2019-02-01 |
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| series | Frontiers in Oncology |
| spelling | doaj.art-93af7f93fd554c18b48c977f8ad59a0f2022-12-21T19:18:58ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2019-02-01910.3389/fonc.2019.00086442063Low-Dose vs. High-Dose Cisplatin: Lessons Learned From 59 Chemoradiotherapy Trials in Head and Neck CancerPetr Szturz0Kristien Wouters1Kristien Wouters2Naomi Kiyota3Makoto Tahara4Kumar Prabhash5Vanita Noronha6David Adelstein7Dirk Van Gestel8Jan B. Vermorken9Jan B. Vermorken10Department of Oncology, Lausanne University Hospital (CHUV), Lausanne, SwitzerlandScientific Coordination and Biostatistics, Antwerp University Hospital, Edegem, BelgiumFaculty of Medicine and Health Sciences, University of Antwerp, Antwerp, BelgiumKobe University Hospital Cancer CenterKobe, JapanDepartment of Head and Neck Medical Oncology, National Cancer Center Hospital East, Kashiwa, JapanDepartment of Medical Oncology, Tata Memorial Hospital, Mumbai, IndiaDepartment of Medical Oncology, Tata Memorial Hospital, Mumbai, IndiaDepartment of Hematology and Medical Oncology, Taussig Cancer Institute, Cleveland Clinic, Cleveland, OH, United StatesDepartment of Radiotherapy, Institut Jules Bordet, Université Libre de Bruxelles, Brussels, BelgiumFaculty of Medicine and Health Sciences, University of Antwerp, Antwerp, BelgiumDepartment of Medical Oncology, Antwerp University Hospital, Edegem, BelgiumIn locally advanced squamous cell carcinomas of the head and neck (LA-SCCHN), concurrent chemoradiotherapy is an integral part of multimodality management both in the adjuvant and in the definitive settings. Although de-intensification strategies have been propelled to the forefront of clinical research in human papillomavirus (HPV) positive oropharyngeal cancer, three cycles of 100 mg/m2 cisplatin given every 3 weeks concurrently with conventionally fractionated external beam radiotherapy represent a cost-effective and globally accessible treatment option for the majority of LA-SCCHN cases. Based on four large randomized trials, this regimen has become the non-surgical standard of care for cisplatin-eligible patients. Nevertheless, the outcomes in terms of efficacy, toxicity, and compliance have been rather disappointing. Therefore, there is an unmet need to find a better alternative. With limited support from randomized trials, weekly low-dose cisplatin regimens have replaced the standard high-dose schedule at some institutions. Four prospective trials exploring radiotherapy with and without weekly low-dose cisplatin have been published. Two of them were conducted in the 1980s, one of which had a negative outcome, the third study provided insufficient information on toxicity, and the fourth trial had to be prematurely terminated due to poor accrual. Moreover, the findings of two phase III trials comparing the two concurrent cisplatin regimens favored the high-dose protocol. We performed a composite meta-analysis of 59 prospective trials enrolling a total of 5,582 patients. The primary endpoint was overall survival. Reflecting different radiotherapy fractionation schemes and treatment intents, three meta-analyses were carried out, one for postoperative conventional chemoradiotherapy, one for definitive conventional chemoradiotherapy, and one for definitive altered fractionation chemoradiotherapy. In the former two settings, both high- and low-dose regimens yielded similar survival outcomes, thus, the primary objective was not met. When given concurrently with altered fractionation radiotherapy, patients treated with high-dose cisplatin had significantly longer overall survival than those who received low-dose cisplatin. In this article we provide a synthetic view of the results, discuss the issue of cumulative dose, compare two vs. three cycles of high-dose cisplatin, and present our three-step recommendations for use of the current standard of care, high-dose cisplatin, in clinical practice.https://www.frontiersin.org/article/10.3389/fonc.2019.00086/fullhead and neck cancerchemoradiotherapyfractionationcisplatinclinical trialscumulative dose |
| spellingShingle | Petr Szturz Kristien Wouters Kristien Wouters Naomi Kiyota Makoto Tahara Kumar Prabhash Vanita Noronha David Adelstein Dirk Van Gestel Jan B. Vermorken Jan B. Vermorken Low-Dose vs. High-Dose Cisplatin: Lessons Learned From 59 Chemoradiotherapy Trials in Head and Neck Cancer Frontiers in Oncology head and neck cancer chemoradiotherapy fractionation cisplatin clinical trials cumulative dose |
| title | Low-Dose vs. High-Dose Cisplatin: Lessons Learned From 59 Chemoradiotherapy Trials in Head and Neck Cancer |
| title_full | Low-Dose vs. High-Dose Cisplatin: Lessons Learned From 59 Chemoradiotherapy Trials in Head and Neck Cancer |
| title_fullStr | Low-Dose vs. High-Dose Cisplatin: Lessons Learned From 59 Chemoradiotherapy Trials in Head and Neck Cancer |
| title_full_unstemmed | Low-Dose vs. High-Dose Cisplatin: Lessons Learned From 59 Chemoradiotherapy Trials in Head and Neck Cancer |
| title_short | Low-Dose vs. High-Dose Cisplatin: Lessons Learned From 59 Chemoradiotherapy Trials in Head and Neck Cancer |
| title_sort | low dose vs high dose cisplatin lessons learned from 59 chemoradiotherapy trials in head and neck cancer |
| topic | head and neck cancer chemoradiotherapy fractionation cisplatin clinical trials cumulative dose |
| url | https://www.frontiersin.org/article/10.3389/fonc.2019.00086/full |
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