A triplet combination with irinotecan (CPT-11), oxaliplatin (LOHP), continuous infusion 5-fluorouracil and leucovorin (FOLFOXIRI) plus cetuximab as first-line treatment in KRAS wt, metastatic colorectal cancer: a pilot phase II trial

Saridaki, Zenia; Androulakis, N.; Vardakis, N.; Vamvakas, L.; Kabouraki, E.; Kalbakis, Kostas; Hatzidaki, Dora; Voutsina, Alexandra; Mavroudis, Dimitris; Georgoulias, Vassilis; Souglakos, John

doi:10.1038/bjc.2012.509

Cited by 51 publications

(44 citation statements)

References 20 publications

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“…Promising evidence of the clinical activity of three-drug chemo therapy plus cetuximab regimens was initially observed in mol ecularly unselected populations in the POCHER, ERBIRINOX and COFI trials (ORR of 79%, 81%, and 75%, respectively), [61][62][63] and then replicated in patients with wild-type KRAS exon 2. 64,65 For example, the phase II trial by Saridaki and colleagues, 64 which evaluated a modified FOLFOXIRI regimen plus cetuximab in 30 patients with KRAS-exon-2-wild-type mCRC, reported an ORR and a radical resection rate of 70% and 37%, respectively. Remarkable therapeutic activity was also demonstrated in the phase II TRIP study, 65 in which the combination of FOLFOXIRI with panitumumab was investi gated in a highly molecularly selected population of 37 patients with unresectable KRAS/NRAS/HRAS/BRAF-wild-type disease; 33 patients (89%) had an objective res ponse and 13 (35%) subsequently underwent radical secondary resection of metastases.…”

Section: Combination With Anti-egfr Agentsmentioning

confidence: 98%

First-line chemotherapy for mCRC—a review and evidence-based algorithm

et al. 2015

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The response to first-line therapy is a primary determinant of outcome in patients with metastatic colorectal cancer (mCRC), for three main reasons: effective upfront therapy provides a unique opportunity to cure some patients; can be crucial in delaying disease progression and achieving symptom relief; and can improve patient eligibility for, and the effectiveness of, further treatments. In the past decade, decision-making regarding the choice of first-line therapy for mCRC has been complicated by the availability of many different options without a definitive consensus on a specific standard of care (despite major advances in categorizing predictive molecular disease subtypes). Most of the efforts of the scientific community have been directed at establishing the best biologic agent to be combined with a chemotherapy doublet, although a different branch of research has produced new data that underscore the importance of defining the optimal chemotherapy backbone. Herein, we review the key clinical trials completed in the past 10 years that have investigated and compared the use of chemotherapy doublets, triplets, and monotherapies, with or without molecularly targeted biologic agents, in the first-line treatment of patients with mCRC. Our examination of the literature led us to propose a new patient-oriented algorithm to guide clinicians' decisions on the best choice of upfront therapy for mCRC.

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Section: Combination With Anti-egfr Agentsmentioning

confidence: 98%

First-line chemotherapy for mCRC—a review and evidence-based algorithm

et al. 2015

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“…Lastly, cetuximab was also evaluated in combination with the triplet FOLFOXIRI in a Phase II trial of patients with wt KRAS mCRC who were younger than 70 years and with 0-1 performance status. 125 The overall RR was 70%, and secondary R0 resections were performed in 37% of patients. In the final report of the PRIME trial, overall RR favored panitumumab plus FOLFOX4 (57% versus 48%, P=0.02) compared to chemotherapy alone in patients with the wt KRAS gene.…”

Section: Secondary Resectabilitymentioning

confidence: 99%

EGFR signaling in colorectal cancer: a clinical perspective

Saletti¹,

Molinari²,

Dosso³

et al. 2015

GICTT

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Colorectal cancer (CRC) remains a formidable health burden worldwide, with up to 50% of patients developing metastases during the course of their disease. This group of CRC patients, characterized by the worst prognosis, has been extensively investigated to improve their life expectancy. Main efforts, focused on the epidermal growth-factor receptor (EGFR), which plays a pivotal role in CRC pathogenesis, have led to the development and introduction in clinical practice of specific targeted therapies (ie, monoclonal antibodies). Subsequently, the scientific community has tried to identify molecular predictors of the efficacy of such therapies. However, it has become clear that EGFR alterations occurring in CRC are difficult to investigate, and therefore their predictive role is unclear. In contrast, the clinical role of two downstream members (KRAS and NRAS) has been clearly demonstrated. Currently, EGFRtargeted therapies can be administered only to patients with wild-type KRAS and NRAS genes. Our review addresses the medical management of metastatic CRC. Specifically, we describe in detail the molecular biology of metastatic CRC, focusing on the EGFR signaling pathway, and we discuss the role of current and emerging related biomarkers and therapies in this field. We also summarize the clinical evidence regarding anti-EGFR monoclonal antibodies and examine potential future perspectives.

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“…The metastasis resection and conversion rates were then evaluated retrospectively and no clear definition of resectability was provided. The efficacy of chemotherapeutic associations in doublets or triplets has been established [ [15], [16], [17], [18], [19], [20], [21]] and afterwards, also the association between chemotherapy and monoclonal antibodies has proven to be effective [ [13], [22], [23], [24], [25], [26], [27], [28], [29], [30], [31], [32], [33], [34], [35], [36]]. The results in terms of OS and overall response rate (ORR) of the main phase II and III studies are summarized in Table 1.…”

Section: Conversion Therapymentioning

confidence: 99%