A randomized two-arm phase III study to investigate bevacizumab in combination with capecitabine plus oxaliplatin (CAPOX) versus CAPOX alone in post radical resection of patients with liver metastases of colorectal cancer.

Voest, Emile E.; Snoeren, Nikol; Schouten, Sander B; Bergman, Andries M.; Werkhoven, Erik van; Loosveld, Olaf; Gulik, T.M. van; Smit, J. M.; Cats, Annemieke; Boven, Epie; Hesselink, E. J.; Rijken, Anouk; Tol, M. Petrousjka van den; Dalesio, O.; Verheul, Henk M.W.; Tollenaar, R.A.E.M.; Sijp, Joost van der; Rinkes, Ihm Borel; Hillegersberg, Richard van

doi:10.1200/jco.2011.29.15_suppl.3565

Cited by 12 publications

(6 citation statements)

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“…The analysis of the 79 patients included showed a favorable but not a significant improvement in DFS at 2 years for bevacizumab (52% vs 72%, P = 0.074). 37 However, the addition of bevacizumab or cetuximab to FOLFOX recently failed to increase DFS in the adjuvant setting after resection of primary colon cancer in 3 phase 3 trials. 38,39 In a recent randomized phase 2 trial, the addition of bevacizumab to adjuvant HAI floxuridine (FUDR) plus IV chemotherapy after resection of CRLM did not seem to increase DFS or OS.…”

Section: Discussionmentioning

confidence: 99%

Adjuvant Chemotherapy After Resection of Colorectal Liver Metastases in Patients at High Risk of Hepatic Recurrence

Goèré

Benhaïm²,

Bonnet³

et al. 2013

Annals of Surgery

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Section: Discussionmentioning

confidence: 99%

Adjuvant Chemotherapy After Resection of Colorectal Liver Metastases in Patients at High Risk of Hepatic Recurrence

Goèré

Benhaïm²,

Bonnet³

et al. 2013

Annals of Surgery

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“…EORTC 40983 (PFS), and to gain information about tolerability and QoL with the four-drug regimen secondary endpoints include these parameters. Perioperative treatment was limited to 6 months, as no conclusive data about prolonged treatment is currently available [ 30 ]. The trial also offers the unique opportunity of collecting tissue from liver metastases and primary tumours either untreated or treated.…”

Section: Discussionmentioning

confidence: 99%

Treatment with bevacizumab and FOLFOXIRI in patients with advanced colorectal cancer: presentation of two novel trials (CHARTA and PERIMAX) and review of the literature

Stein

Glockzin²,

Wienke

et al. 2012

BMC Cancer

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BackgroundMore than half of patients with colorectal cancer will develop metastatic disease either evident at the time of initial diagnosis or during their course of disease. Besides multidisciplinary management further treatment intensification is warranted to improve the still limited prognosis.Methods/designIn these two multi-centre, randomized phase II trials, conducted in Germany, 380 patients with R0-resectable colorectal liver metastases (PERIMAX) and with unresectable, metastatic colorectal cancer (CHARTA) will be recruited. Patients previously untreated for metastatic disease with either synchronous or metachronous metastases are randomly assigned in a 1:1 ratio to resection of colorectal liver metastases followed by postoperative FOLFOX for 6 months or perioperative FOLFOXIRI and bevacizumab for 3 months pre- and postoperative and resection (PERIMAX), or to induction chemotherapy with FOLFOX and bevacizumab +/− irinotecan for a maximum of 6 months followed by maintenance treatment with fluoropyrimidine and bevacizumab. The primary objective of these trials is to evaluate the feasibility and efficacy of FOLFOXIRI and bevacizumab in metastatic colorectal cancer. Primary endpoint is failure free survival rate at 18 months in the PERIMAX trial and progression free survival rate at 9 months in CHARTA. Secondary objectives include efficacy, safety and tolerability.DiscussionThe CHARTA and PERIMAX trials are designed to evaluate the benefits and limitations of a highly active four-drug regimen in distinct treatment situations of metastatic CRC. Eligible patients are classified into resectable liver metastases to be randomized to perioperative treatment with FOLFOXIRI and bevacizumab or postoperative FOLFOX in the PERIMAX, or unresectable metastatic CRC to be randomized between FOLFOX and bevacizumab with or without irinotecan, stratified for clinical groups according to disease and patients’ characteristics in the CHARTA trial.Trial registrationClinical trial identifier CHARTA: NCT01321957, PERIMAX: NCT01540435

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“…However, postoperative chemotherapy with FOLFOX plus bevacizumab is often administered despite the lack of data supporting this regimen. In the interim analysis of the Dutch HEPATICA trial [66] reported at the 2011 ASCO Annual Meeting, bevacizumab plus capecitabine and oxaliplatin (CAPOX) as postoperative adjuvant chemotherapy provided no significant benefit compared with CAPOX alone in 2-year DFS rate (70% vs 52%, P = 0.074), and exhibited no significant differences in toxicity. For patients who received targeted therapy and responded before surgery, it is reasonable to continue targeted therapy as a postoperative adjuvant treatment.…”

Section: Adjuvant Treatmentmentioning

confidence: 95%

“…Then in the NORDIC-Ⅶ trial [29] , patients with wild type KRAS derived no benefit from cetuximab plus FLOX (fluorouracil, leucovorin, and oxaliplatin) in the primary end point PFS (median PFS, 8.7 mo vs 7.9 mo, P = 0. 66 …”

Section: First-line Treatmentmentioning

confidence: 97%

Anti-EGFR and anti-VEGF agents: Important targeted therapies of colorectal liver metastases

Feng

Chen

et al. 2014

WJG

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Colorectal liver metastasis (CLM) is common worldwide. Targeted therapies with monoclonal antibodies have been proven effective in numerous clinical trials, and are now becoming standards for patients with CLM. The development and application of anti-epidermal growth factor receptor (anti-EGFR) and anti-vascular endothelial growth factor (anti-VEGF) antibodies represents significant advances in the treatment of this disease. However, new findings continue to emerge casting doubt on the efficacy of this approach. The Kirsten rat sarcoma viral oncogene (KRAS) has been proven to be a crucial predictor of the success of anti-EGFR treatment in CLM. Whereas a recent study summarized several randomized controlled trials, and showed that patients with the KRAS G13D mutation significantly benefited from the addition of cetuximab in terms of progress-free survival (PFS, 4.0 mo vs 1.9 mo, HR = 0.51, P = 0.004) and overall survival (OS, 7.6 mo vs 5.7 mo, HR = 0.50, P = 0.005). Some other studies also reported that the KRAS G13D mutation might not be absolutely predictive of non-responsiveness to anti-EGFR therapy. At the same time, "new" RAS mutations, including mutations in neuroblastoma RAS viral (v-ras) oncogene homolog (NRAS) and exons 3 and 4 of KRAS, have been suggested to be predictors of a poor treatment response. This finding was first reported by the update of the PRIME trial. The update showed that for patients with non-mutated KRAS exon 2 but other RAS mutations, panitumumab-fluorouracil, leucovorin, and oxaliplatin (FOLFOX)4 treatment led to inferior PFS (HR = 1.28, 95%CI: 0.79-2.07) and OS (HR = 1.29, 95%CI: 0.79-2.10), which was consistent with the findings in patients with KRAS mutations in exon 2. Then, the update of the PEAK trial and the FIRE-III trial also supported this finding, which would reduce candidates for anti-EGFR therapy but enhance the efficacy. In first-line targeted combination therapy, the regimens of cetuximab plus FOLFOX was called into question because of the inferior prognosis in the COIN trial and the NORDIC-VII trial. Also, bevacizumab plus oxaliplatin-based chemotherapy was questioned because of the NO16966 trial. By the update and further analysis of the COIN trial and the NORDIC-VII trial, cetuximab plus FOLFOX was reported to be reliable again. But bevacizumab plus oxaliplatin-based chemotherapy was still controversial. In addition, some trials have reported that bevacizumab is not suitable for conversion therapy. The results of the FIRE-III trial showed that cetuximab led to a significant advantage over bevacizumab in response rate (72% vs 63%, P = 0.017) for evaluable population. With the balanced allocation of second-line treatment, the FIRE-III trial was expected to provide evidence for selecting following regimens after first-line progression. There is still no strong evidence for the efficacy of targeted therapy as a preoperative treatment for resectable CLM or postoperative treatment for resected CLM, although the combined regimen is often administered based on experience. C...

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A randomized two-arm phase III study to investigate bevacizumab in combination with capecitabine plus oxaliplatin (CAPOX) versus CAPOX alone in post radical resection of patients with liver metastases of colorectal cancer.

Cited by 12 publications

References 0 publications

Adjuvant Chemotherapy After Resection of Colorectal Liver Metastases in Patients at High Risk of Hepatic Recurrence

Adjuvant Chemotherapy After Resection of Colorectal Liver Metastases in Patients at High Risk of Hepatic Recurrence

Treatment with bevacizumab and FOLFOXIRI in patients with advanced colorectal cancer: presentation of two novel trials (CHARTA and PERIMAX) and review of the literature

Anti-EGFR and anti-VEGF agents: Important targeted therapies of colorectal liver metastases

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