Elsevier

European Journal of Cancer

Volume 47, Issue 17, November 2011, Pages 2512-2516
European Journal of Cancer

Tumour growth rates and RECIST criteria in early drug development

https://doi.org/10.1016/j.ejca.2011.06.012Get rights and content

Abstract

Purpose

The evaluation of treatment efficacy with RECIST criteria does not take into account tumour growth dynamics. We notably investigated the impact of the pre-treatment tumour growth rate (GR) on the evaluation of treatment response.

Patients and methods

Seventy-six patients included in phase I clinical trials had scanographic evaluations before and after starting an experimental treatment. The GR was calculated for the pre-treatment period and for the experimental period (i.e. during the new treatment). Tumour response was evaluated per protocol at week 12 and at week 24 of the experimental period according to RECIST criteria. We studied the relation between pre-treatment and experimental GRs and RECIST tumour response.

Results

On average the tumour GR was decreased by 40% during the experimental period; compared to the pretreatment period (p = 0.03). An increased growth rate (acceleration of GR during experimental treatment compared to pretreatment) was observed in 20 (38%) of the 53 patients considered as non-progressive at week 12 according to RECIST. Conversely a decreased GR was observed in 12 out of 23 (53%) patients classified as progressive according to RECIST. The variation in the GR between the pre-treatment and experimental period was not significantly correlated with response evaluated according to RECIST at week 12 or at week 24 (p = 0.45 and 0.44, respectively).

Conclusions

RECIST evaluation of tumour response depends on the natural history of the tumours and poorly measures the impact of treatment on the kinetics of tumour growth. Integrating pre-treatment GR evaluations could substantially improve the assessment of treatment efficacy in 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.

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