A systematic methodology review of phase I radiation dose escalation trials

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• 作者：Madelon Pijls-Johannesma ; Ghislaine van Mastrigt ; Steve M. Hahn ; Dirk De Ruysscher ; Brigitta G. Baumert ; Guido Lammering ; Jeroen Buijsen ; Soren M. Bentzen ; Yol ; e Lievens ; Andrew Kramar ; Philippe Lambi
• 关键词：Systematic review ; Radiotherapy and clinical trial phase I
• 刊名：Radiotherapy and Oncology
• 出版年：2010
• 出版时间：May 2010
• 年：2010
• 卷：95
• 期：2
• 页码：135-141
• 全文大小：201 K

文摘

Background and purpose

The purpose of this review is to evaluate the methodology used in published phase I radiotherapy (RT) dose escalation trials. A specific emphasis was placed on the frequency of reporting late complications as endpoint.

Materials and methods

We performed a systematic literature review using a predefined search strategy to identify all phase I trials reporting on external radiotherapy dose escalation in cancer patients.

Results

Fifty-three trials (phase I: n = 36, phase I–II: n = 17) fulfilled the inclusion criteria. Of these, 20 used a modified Fibonacci design for the RT dose escalation, but 32 did not specify a design. Late toxicity was variously defined as >3 months (n = 43) or > 6 months (n = 3) after RT, or not defined (n = 7). In only nine studies the maximum tolerated dose (MTD) was related to late toxicity, while only half the studies reported the minimum follow-up period for dose escalation (n = 26).

Conclusion

In phase I RT trials, late complications are often not taken into account and there is currently no consensus on the methodology used for radiation dose escalation studies. We therefore propose a decision-tree algorithm which depends on the endpoint selected and whether a validated early surrogate endpoint is available, in order to choose the most appropriate study design.