Early tumour shrinkage (ETS) and depth of response (DpR) in the treatment of patients with metastatic colorectal cancer (mCRC)

Abstract

Background: Response evaluation criteria in solid tumours (RECIST) are used to define degrees of response to anti-tumour agents. In retrospective analyses, early tumour shrinkage (ETS) has been investigated as an alternative early-on-treatment predictor of treatment efficacy with regard to progression-free and overall survival. While cut-off based analysis of ETS facilitates the categorisation of patients into responders and non-responders after a defined period of treatment, depth of response (DpR) serves as a continuous measure, which defines the nadir of tumour response.

Methods: A systematic literature search for 'early tumour shrinkage' or 'tumour size decrease' in 'metastatic colorectal cancer' reported from January 2000 to July 2014 was performed. The present review summarises available data concerning ETS and DpR and evaluates their potential as predictive markers for the clinical management of patients with metastatic colorectal cancer (mCRC).

Results: A total of 10 clinical trials investigated the role of ETS as a marker of clinical outcome in patients with mCRC. In addition, DpR was investigated using the efficacy data from three of these trials. Available data show that ETS differentiates patients with high sensitivity to treatment and more favourable prognosis from a heterogeneous group of patients classified as non-ETS patients. ETS is an early indicator of the potentially achievable response. In contrast, DpR estimates the nadir of tumour response as a continuous measure, which may affect the subsequent disease history, thus translating into superior survival.

Conclusions: The concepts of ETS and DpR offer potential as clinical end-points to aid the clinical decision making process and thus further optimise mCRC patient management in the era of tailored therapy approaches.

Keywords: Cetuximab; Chemotherapy; Depth of response; Early tumour shrinkage; Metastatic colorectal cancer; Targeted therapy.