Different strategies of sequential and combination chemotherapy for patients with poor prognosis advanced colorectal cancer (MRC FOCUS): a randomised controlled trial

Seymour, Michel; Maughan, T; Ledermann, Jonathan A.; Topham, C.; James, Roger D; Gwyther, Stephen J.; Smith, David B.; Shepherd, S.F.; Maraveyas, Anthony; Ferry, David; Meade, Angela; Thompson, Lindsay C; Griffiths, Gareth; Parmar, Mahesh; Stephens, Richard

doi:10.1016/s0140-6736(07)61087-3

Cited by 509 publications

(314 citation statements)

References 26 publications

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“…Individual patient data were obtained from selected arms of three large randomised trials (FOCUS [ISRCTN 79877428], [13] COIN [ISRCTN 27286448], [14,15] PICCOLO [ISRCTN 93248876] [16,17] to reflect different clinical uses of standard cytotoxic chemotherapy (without targeted therapy) in aCRC (Supplementary Figure 1).…”

Section: Introductionmentioning

confidence: 99%

Investigating the poor outcomes ofBRAF-mutant advanced colorectal cancer: analysis from 2530 patients in randomised clinical trials

et al. 2017

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Section: Introductionmentioning

confidence: 99%

Investigating the poor outcomes ofBRAF-mutant advanced colorectal cancer: analysis from 2530 patients in randomised clinical trials

et al. 2017

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“…This finding had been observed in an earlier IDMC report and the TMG had, on the instruction of the IDMC, improved the patient information cards and fed back the data to investigators so that they include this information in their discussions with patients regarding selection of capecitabine-or 5FU-based treatment. Despite this, the rate of diarrhoea was gradually increasing: for those patients receiving oxaliplatin, capecitabine and cetuximab, a grade 3/4 diarrhoea rate of 23% was reported in the ASCO abstract (Maughan, 2007) submitted in December 2006 and this had reached 30% (on the data set from the March IDMC, released to the TMG as of July 2007). Thus, there was no sign of an improvement with greater experience of the regime by investigators despite information to investigators and improved patient information.…”

Section: Discussionmentioning

confidence: 99%

Toxicity associated with combination oxaliplatin plus fluoropyrimidine with or without cetuximab in the MRC COIN trial experience

et al. 2009

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We present the preliminary toxicity data from the MRC COIN trial, a phase III randomised controlled trial of first-line therapy in advanced colorectal cancer, with particular reference to the addition of cetuximab to an oxaliplatin -fluoropyrimidine combination. A total of 804 patients were randomised between March 2005 and July 2006 from 78 centres throughout the United Kingdom. Patients were allocated to oxaliplatin plus fluoropyrimidine chemotherapy with or without the addition of weekly cetuximab. The choice of fluoropyrimidine (either 5-fluorouracil (5FU) or capecitabine) was decided by the treating physician and patient before randomisation. Toxicity data were collected from all patients. Two hundred and three patients received 5FU plus oxaliplatin (OxMdG, 25%), 333 oxaliplatin þ capecitabine (Xelox, 41%), 102 received OxMdG þ cetuximab (OxMdG þ C, 13%) and 166 Xelox þ cetuximab (21%). Percent grade 3/4 toxicities included diarrhoea 6, 15, 13 and 25%, nausea/vomiting 3, 7, 7 and 14% for OxMdG, Xelox, OxMdG þ C and Xelox þ C, respectively. Sixty-day all-cause mortality was 6, 5, 5 and 7%. Statistically significant differences were evident for patients receiving Xelox þ cetuximab vs Xelox alone: diarrhoea relative risk (RR) 1.69 (1.17, 2.43, P ¼ 0.005) and nausea/vomiting RR 2.01 (1.16, 3.47, P ¼ 0.012). The excess toxicity observed in the oxaliplatin-, capecitabine-, cetuximab-treated patients led the trial management group to conclude that a capecitabine dose adjustment was required to maintain safety levels when using this regimen.

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“…Recently, the largest published RCT in advanced CRC, FOCUS (Seymour et al, 2007a), reported the first results of a nested prospective search for biomarkers within the FOCUS study (Braun et al, 2008). Topo 1, a molecular target of SN38 (active metabolite of irinotecan) was found to be a predictive biomarker to irinotecan therapy in the assessable 1313 patients.…”

Section: Biomarkers For Efficacy and Toxicitymentioning

confidence: 99%

Treatment in advanced colorectal cancer: what, when and how?

Chau

Cunningham

2009

Br J Cancer

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Treatment of advanced colorectal cancer (CRC) increasingly requires a multidisciplinary approach and multiple treatment options add to the complexity of clinical decision-making. Recently novel targeted therapy against angiogenesis and epidermal growth factor receptor completed a plethora of phase III studies. The addition of bevacizumab to chemotherapy improved the efficacy over chemotherapy alone in both first and second line settings, although the magnitude of benefit may not be as great when a more optimal chemotherapy platform is used. Studies performed thus far did not address conclusively whether bevacizumab should be continued in subsequent lines of treatment. Anti-angiogenesis tyrosine kinase inhibitors have not shown any additional benefit over chemotherapy alone so far. Although some benefits were seen with cetuximab in all settings of treating advanced CRC, K-ras mutation status provides an important determinant of who would not benefit from such a treatment. Caution should be exercised in combining anti-angiogenesis with anti-EGFR strategy until further randomised data become available. In this review, we have focused on the implications of these trial results on the everyday management decisions of treating advanced CRC.

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Different strategies of sequential and combination chemotherapy for patients with poor prognosis advanced colorectal cancer (MRC FOCUS): a randomised controlled trial

Cited by 509 publications

References 26 publications

Investigating the poor outcomes ofBRAF-mutant advanced colorectal cancer: analysis from 2530 patients in randomised clinical trials

Investigating the poor outcomes ofBRAF-mutant advanced colorectal cancer: analysis from 2530 patients in randomised clinical trials

Toxicity associated with combination oxaliplatin plus fluoropyrimidine with or without cetuximab in the MRC COIN trial experience

Treatment in advanced colorectal cancer: what, when and how?

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