Tumour growth rates and RECIST criteria in early drug development
Introduction
RECIST (Response Evaluation Criteria in Solid Tumours) is the standard guideline for assessing tumour response for most clinical trials in oncology.1 Response evaluation is based on a comparison between the measurement of several targets just before the start of the new treatment and measurement of the same targets at specific times during the course of the new treatment.
RECIST evaluations do not take into account tumour growth characteristics and notably its pre-treatment component. Thus, the categorisation of tumour response according to RECIST criteria may not reflect the ability of an anticancer treatment to modify tumour growth by inducing some degree of tumour regression or by slowing down tumour growth.
We evaluated the possible influence of pre-treatment tumour growth characteristics on treatment evaluation according to RECIST and investigated the feasibility and impact of using pre-treatment evaluations of the tumour growth rate to improve the evaluation of treatment efficacy.
Section snippets
Material and methods
All patients included in phase I trials at Institut de cancérologie Gustave Roussy (IGR) between January 2005 and July 2008, who had at least two CT-scan evaluations before the start of an experimental treatment, a baseline CT-scan (D0), and at least one evaluation after D0 were eligible. Seventy-six of 317 patients included in our phase I trials during that time-frame met these criteria. The remaining 241 patients were not included because they had fewer than two pre-treatment CT-scans
Results
Patient characteristics are summarised in Table 1. The median number of previous tumour treatment lines was 3. A total of 370 evaluations were performed: 76 before D0, 76 at D0 and 218 after the initiation of the experimental treatment. The median number of lesions monitored per patient was 3. At week 12, 23 patients were classified in progression, and 54 at week 24.
Discussion
This study aimed at evaluating the feasibility and usefulness of measuring the tumour growth rate during the pre-treatment and experimental period in order to better apprehend treatment efficacy.
As expected, the growth rate measured during the experimental period was significantly correlated with the evaluation of response according to the RECIST criteria. Patients classified with the higher growth rates were those classified as exhibiting progression according to RECIST. This finding mainly
Conclusion
Pre-treatment growth dynamics adds to the RECIST evaluation of tumour response and thus should be carefully documented. Patients with slow growing tumours are likely to be classified as disease control; even if the treatment has a minimal effect. Conversely, evaluation of an active new treatment on patients with fast growing tumours might unduly lead to early termination of a promising compound. The evaluation of response to experimental therapies or to recognised therapies should take into
Funding source
None.
Conflict of interest statement
None declared.
Acknowledgements
We are in debt with Mrs. Lorna Saint-Ange for her invaluable editing assistance.
References (4)
- et al.
New response evaluation criteria in solid tumors: revised RECIST guideline (version 1.1)
Eur J Cancer
(2009) - et al.
New guidelines to evaluate the response to treatment in solid tumors. European Organization for Research and Treatment of Cancer, National Cancer Institute of the United States, National Cancer Institute of Canada
J Natl Cancer Inst
(2000)