title: Thirty years of phase I radiochemotherapy trials: Latest development.
abstract: Radiochemotherapy is undergoing a complete expansion. Currently, possibilities of treatment combination are skyrocketting, with different anticancer and targeted molecules, different radiotherapy techniques, and dose escalation with each therapy. The development of a modern phase I radiochemotherapy trial becomes more and more complex and should be fully investigated. In the literature, there are no exhaustive reviews describing the necessity of their characteristics. The present article explores historical and current phase I clinical trials involving a combination of radiation therapy and anticancer therapies. Selected trials were identified by searching in PubMed databases. A total of 228 studies were identified in the last three decades, and a portrait of their characteristics is presented. As expected, most frequently studied malignancies were head and neck cancers, followed by non-small cell lung cancer and brain cancer. Toxicity is reported in more than 90% of the studies. Most studies were published since 2010, at the area of targeted therapies, but mainly concerned classical chemotherapies (cisplatin and 5-fluorouracil). The present review highlights some limits. Indeed, methodology seems not optimised and could be based on more accurate methods of dose-escalation. The present portrait of phase I radiochemotherapy trials suggests that radiochemotherapy notion must be reinvented and trials should be adapted to its complexity. Step by step method does not sound like an option anymore. Let us build the future of radiochemotherapy on past evidences.
authors.affiliation: Department of Medical Oncology, Lucien Neuwirth Cancer Institute, Saint Priest-en-Jarez, France.
authors.forename: Romain
authors.initials: R
authors.lastname: Rivoirard
authors.affiliation: Department of Radiotherapy, Lucien Neuwirth Cancer Institute, Saint Priest-en-Jarez, France.
authors.forename: Alexis
authors.initials: A
authors.lastname: Vallard
authors.affiliation: Department of Radiotherapy, Lucien Neuwirth Cancer Institute, Saint Priest-en-Jarez, France.
authors.forename: Julien
authors.initials: J
authors.lastname: Langrand-Escure
authors.affiliation: Department of Radiotherapy, Lucien Neuwirth Cancer Institute, Saint Priest-en-Jarez, France.
authors.forename: Majed
authors.initials: M
authors.lastname: Ben Mrad
authors.affiliation: Department of Radiotherapy, Lucien Neuwirth Cancer Institute, Saint Priest-en-Jarez, France.
authors.forename: Guoping
authors.initials: G
authors.lastname: Wang
authors.affiliation: Department of Radiotherapy, Lucien Neuwirth Cancer Institute, Saint Priest-en-Jarez, France.
authors.forename: Jean-Baptiste
authors.initials: JB
authors.lastname: Guy
authors.affiliation: Department of Radiotherapy, Lucien Neuwirth Cancer Institute, Saint Priest-en-Jarez, France.
authors.forename: Peng
authors.initials: P
authors.lastname: Diao
authors.affiliation: Department of Radiotherapy, Lucien Neuwirth Cancer Institute, Saint Priest-en-Jarez, France.
authors.forename: Alexandre
authors.initials: A
authors.lastname: Dubanchet
authors.affiliation: Department of Molecular Radiotherapy, Gustave Roussy Cancer Campus, Paris, France.
authors.forename: Eric
authors.initials: E
authors.lastname: Deutsch
authors.affiliation: Department of Radiotherapy, Lucien Neuwirth Cancer Institute, Saint Priest-en-Jarez, France.
authors.forename: Chloe
authors.initials: C
authors.lastname: Rancoule
authors.affiliation: Department of Radiotherapy, Lucien Neuwirth Cancer Institute, Saint Priest-en-Jarez, France. Electronic address: nicolas.magne@icloire.fr.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Magne
mesh_terms: D059248:Chemoradiotherapy / Q000009:adverse effects / Q000266:history / Q000639:trends; D017321:Clinical Trials, Phase I as Topic / Q000266:history; D049673:History, 20th Century; D049674:History, 21st Century; D006801:Humans; D009369:Neoplasms / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D011829:Radiation Dosage; D016896:Treatment Outcome
keywords: Clinical trials, phase I as topic; Concomitant radiochemotherapy; Dose escalation; Maximum tolerated dose; Research design; Review; Targeted therapies