Early tumour response as a survival predictor in previously- treated patients receiving triplet hepatic artery infusion and intravenous cetuximab for unresectable liver metastases from wild-type KRAS colorectal cancer

Abstract

2016) Early tumour response as a survival predictor in previously-treated patients receiving triplet hepatic artery infusion and intravenous cetuximab for unresectable liver metastases from wild-type KRAS colorectal cancer. European Journal of Cancer Care, 68. pp. 163-172 Permanent WRAP URL: http://wrap.warwick.ac.uk/85119 Copyright and reuse:The Warwick Research Archive Portal (WRAP) makes this work by researchers of the University of Warwick available open access under the following conditions. Copyright © and all moral rights to the version of the paper presented here belong to the individual author(s) and/or other copyright owners. To the extent reasonable and practicable the material made available in WRAP has been checked for eligibility before being made available.Copies of full items can be used for personal research or study, educational, or not-for profit purposes without prior permission or charge. Provided that the authors, title and full bibliographic details are credited, a hyperlink and/or URL is given for the original metadata page and the content is not changed in any way. Publisher's statement:"This is the peer reviewed version of the following article: Bouchahda, Mohamed, Boige, Valérie, Smith, Denis, Karaboué, Abdoulaye, Ducreux, Michel, Hebbar, Mohamed, Lepère, Céline, Focan, Christian, Guimbaud, Rosine, Innominato, Pasquale F. et al.. (2016) Early tumour response as a survival predictor in previously-treated patients receiving triplet hepatic artery infusion and intravenous cetuximab for unresectable liver metastases from wild-type KRAS colorectal cancer. European Journal of Cancer Care, 68. pp. 163-172 which has been published in final form at http://dx.doi.org/10.1016/j.ejca.2016.09.011 This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-Archiving." A note on versions:The version presented here may differ from the published version or, version of record, if you wish to cite this item you are advised to consult the publisher's version. Please see the 'permanent WRAP URL' above for details on accessing the published version and note that access may require a subscription. within a multicenter conversion-to-resection medico-surgical strategy. Confirmation is warranted for decision-making. Protocol numbersEUDRACT 2007-004632-24 NCT00852228 KEY WORDS:Early tumor response, colorectal cancer, liver metastases, hepatic artery infusion, triplet chemotherapy. ACKNOWLEDGEMENTS:We sincerely acknowledge the contribution of the patients who participated in this trial and all our colleagues and staff at the participating institutions.

Conversion of Unresectable to Resectable Liver Metastases from Colorectal Carcinoma Using Hepatic Arterial Chronomodulated Chemotherapy: A Case Report and Short Literature Review

“…The main end point was met, achieving a complete macroscopic resection rate of CLM in nearly 30% of all included patients with initially unresectable CLM [14]. Moreover, subgroup analysis suggested that the survival benefit from the liver-targeted chemo-surgery strategy was largely better in the patients receiving irinotecan, oxaliplatin and 5-FU as a chronomodulated hepatic artery infusion [16]. Several recent studies have reported that patients with right-sided primary tumours have worse survival outcomes and it is possible that these patients benefit less from standard therapies [20].…”

Pharmacogenetic determinants of outcomes on triplet hepatic artery infusion and intravenous cetuximab for liver metastases from colorectal cancer (European trial OPTILIV, NCT00852228)

“…All patients received OPTILIV protocol treatment consisting in biweekly administration of hepatic artery infusion of IFO, combined to intravenous infusion of cetuximab. Hepatic artery infusion was administered either as a conventional modality or according to chronomodulated delivery, according to institution experience ( Bouchahda et al , 2016 ; Levi et al , 2016 ).…”

“…Tumour response imaging was obtained every three courses and classified according to RECIST. Patients were assessed for secondary liver surgery at iterative oncosurgical evaluations after three, six or nine cycles ( Bouchahda et al , 2016 ).…”

“…As an example, hepatic artery infusion (HAI) of irinotecan, 5-fluorouracil (F) and oxaliplatin (O) (IFO) was recently combined with intravenous cetuximab in previously treated patients with liver metastases from colorectal cancer (LM-CRC) within European Phase II clinical trial OPTILIV ( Levi et al , 2016 ). The conversion rate of previously unresectable LM to curative intent hepatectomy (R0–R1) reached 30%, and overall median survival was 25 months despite protocol application as median third-line chemotherapy ( Bouchahda et al , 2016 ; Levi et al , 2016 ). Achieving early rather than late tumour shrinkage has indeed become an important goal of chemotherapy of LM-CRC, as it can translate into previously unforeseen surgical resections with prolonged survival or cure ( Bismuth et al , 1996 ; Giacchetti et al , 1999 ; Adam et al , 2004 ).…”

Optimal detection of clinically relevant mutations in colorectal carcinoma: sample pooling overcomes intra-tumoral heterogeneity

“…5,[7][8][9][10]13 Intra-tumoral heterogeneity may cause false negative clinical test results leading to unnecessary treatment with ineffective, costly agents that can cause significant side effects. 9,14 The multi-step model for colorectal carcinogenesis proposed by Fearon and Vogelstien posits that certain gene mutations (eg, APC, KRAS) are early events in the development of colorectal carcinoma; while other gene mutations (eg, TP53) are later events. 15 Based on this wellestablished model, the intra-tumoral heterogeneity of early drivers such as KRAS mutation is expected to be significantly lower than that observed for later secondary alterations such as TP53 or PIK3CA mutation.…”