Combination of Irinotecan, Oxaliplatin and 5-Fluorouracil as a Rechallenge Regimen for Heavily Pretreated Metastatic Colorectal Cancer Patients

Fernandes, Gustavo dos Santos; Braghiroli, Maria Ignez; Artioli, M; Paterlini, Ana Carolina Carvalho Rocha; Teixeira, Marcela Crosara; Gumz, Brenda Pires; Girardi, Daniel M.; Braghiroli, Oddone Freitas Melro; Costa, Frederico; Hoff, Paulo M.

doi:10.1007/s12029-017-0001-3

Cited by 13 publications

(7 citation statements)

References 20 publications

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“…Based on intent-to-treat analysis, the STEAM trial reported TEAE leading to withdrawal with 41% and 38% for the 3-drug plus Bev and 2-drug plus Bev, respectively. However, several trials and reviews, including the RCTs included in this meta-analysis, suggested that the toxicity from FOLFOXIRI-Bev is tolerable and manageable [15,35,36] of adverse events of FOLFOXIRI-Bev was summarized in a review [37]. For diarrhea, loperamide, probiotics, octreotide or tincture of opium may be effective prevention agents.…”

Section: Cellular Physiology and Biochemistrymentioning

confidence: 99%

Triplet Chemotherapy (FOLFOXIRI) Plus Bevacizumab Versus Doublet Chemotherapy (FOLFOX/FOLFIRI) Plus Bevacizumab in Conversion Therapy for Metastatic Colorectal Cancer: a Meta-Analysis

Lin

et al. 2018

Cell Physiol Biochem

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Background/Aims: Conversion therapy can convert unresectable metastatic colorectal cancer (mCRC) into resectable. However, the optimal conversion regimen was not yet defined. This meta-analysis aimed to compare the efficacy and safety of the triplet chemotherapy (FOLFOXIRI) plus bevacizumab (Bev) with doublet chemotherapy (FOLFOX/FOLFIRI) plus Bev in conversion therapy. Methods: Randomized controlled trials (RCTs) from databases, including Pubmed, EMBASE, Cochrane clinical trials, clinicaltrial.gov and some conferences, were searched from the inception to November 2017. The R0 resection, objective response rate (ORR), progression-free survival (PFS), overall survival (OS) and the incidence of adverse events were pooled with the use of hazard ratio (HR) or risk ratio (RR). Results: Four RCTs with 1013 patients were included. FOLFOXIRI plus Bev regimen significantly improved the overall R0 resection rate (RR 1.41, 95% confidence interval (CI) 1.07-1.85, I²=37%), liver R0 resection rate (RR 2.28, 95% CI 1.34-3.89, I²=0%), ORR (RR 1.20, 95% CI 1.09-1.32, I²=0%), PFS (HR 0.72, 95% CI 0.62-0.84, I²=36%) and OS (HR 0.80, 95% CI 0.66-0.97, I²=0%). There was no significant difference in any Grade≥3 adverse event (RR 1.08, 95% CI 0.99-1.17, I²=0%) between two regimens. FOLFOXIRI-Bev was associated with a higher risk of neutropenia (RR 1.77, 95% CI 1.13-2.79, I²=68%) and diarrhea (RR 1.65, 95% CI 1.17-2.32, I²=0%). Conclusions: Triplet chemotherapy plus Bev significantly improved the R0 resection rates, ORR, PFS and OS in comparison with doublet chemotherapy plus Bev in conversion therapy for mCRC patients, with a higher risk of neutropenia and diarrhea.

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Section: Cellular Physiology and Biochemistrymentioning

confidence: 99%

Triplet Chemotherapy (FOLFOXIRI) Plus Bevacizumab Versus Doublet Chemotherapy (FOLFOX/FOLFIRI) Plus Bevacizumab in Conversion Therapy for Metastatic Colorectal Cancer: a Meta-Analysis

Lin

et al. 2018

Cell Physiol Biochem

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“…5b). 5-FU, irinotecan (topoisomerase I inhibitor (TOP1)), and oxaliplatin (new-generation platinum compound) are currently used as first-line active chemotherapy options individually or in combination for patients with metastatic disease 4,43,44 . We did not see a significant effect of cell viability for irinotecan or oxaliplatin using our HT29 RAMS11 overexpressing cells or LoVo RAMS11 CRISPR KO cells (Supplementary Data 3, Supplementary Fig 5c-e).…”

mentioning

confidence: 99%

Long non-coding RNA RAMS11 promotes metastatic colorectal cancer progression

et al. 2020

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Colorectal cancer (CRC) is the most common gastrointestinal malignancy in the U.S.A. and approximately 50% of patients develop metastatic disease (mCRC). Despite our understanding of long non-coding RNAs (lncRNAs) in primary colon cancer, their role in mCRC and treatment resistance remains poorly characterized. Therefore, through transcriptome sequencing of normal, primary, and distant mCRC tissues we find 148 differentially expressed RNAs Associated with Metastasis (RAMS). We prioritize RAMS11 due to its association with poor diseasefree survival and promotion of aggressive phenotypes in vitro and in vivo. A FDA-approved drug high-throughput viability assay shows that elevated RAMS11 expression increases resistance to topoisomerase inhibitors. Subsequent experiments demonstrate RAMS11-dependent recruitment of Chromobox protein 4 (CBX4) transcriptionally activates Topoisomerase II alpha (TOP2α). Overall, recent clinical trials using topoisomerase inhibitors coupled with our findings of RAMS11-dependent regulation of TOP2α supports the potential use of RAMS11 as a biomarker and therapeutic target for mCRC.

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“…or without targeted therapy [3][4][5][6][7] . Unfortunately, despite these treatments, overall survival (OS) of this population is poor with a <12% survival rate at 5 years 2 .…”

mentioning

confidence: 99%

“…A substantial proportion of patients have been noted to retain a relatively good performance status after previous standard chemotherapy, which motivates them to undergo further therapy. Because of the unavailability of regorafenib and TAS102 in China at a certain time, numerous exploratory trials have evaluated oxaliplatin-reinduction chemotherapy and salvage chemotherapy with new combinations [3][4][5][6] . However, the efficacy of subsequent chemotherapies has been discouraging.…”

mentioning

confidence: 99%

Apatinib Monotherapy for Chemotherapy-Refractory Metastatic Colorectal Cancer: A Multi-centre, Single-Arm, Prospective Study

Wang

Yuan

Jia

et al. 2020

Sci Rep

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Angiogenesis inhibitors are of considerable interest for treating metastatic colorectal cancer (mcRc). This trial evaluated the efficacy and safety of apatinib in chemotherapy-refractory mCRC. Apatinib 500 mg was administered daily to patients who had progressed after two or more lines of standard fluorouracil-based chemotherapy. Primary endpoint was progression-free survival (PFS). Secondary endpoints were objective response rate (ORR), disease control rate (DCR), overall survival (OS), and toxicity. Overall, 48 patients were enrolled. ORR and DCR were 8.3% (4/48) and 68.8% (33/48), respectively. Median PFS and OS were 4.8 (95% confidence interval [CI], 3.653-5.887) and 9.1 months (95% CI, 5.155-13.045), respectively, and did not differ between subgroups stratified by previous anti-angiogenic therapies. The most prevalent grade 3-4 adverse events were hypertension (12.5%), hand-foot syndrome (HFS, 10.4%), thrombocytopenia (10.4%), and proteinuria (8.3%). Low baseline neutrophil/lymphocyte ratio (NLR, hazard ratios [HR], 0.619; P = 0.027), early carbohydrate antigen 19-9 (CA19-9) decrease (HR, 1.654; P = 0.016), and HFS (HR, 2.087; P = 0.007) were associated with improved PFS. In conclusion, apatinib monotherapy demonstrated encouraging efficacy with manageable toxicities in chemotherapy-refractory mcRc. previous anti-angiogenic therapies did not influence outcomes. Baseline NLR, early CA19-9 decrease, and HFS could predict the efficacy of apatinib. Colorectal cancer (CRC) remains the third leading cancer globally 1 , and approximately 40-50% patients present with advanced disease at diagnosis 2. Until recently, the standard of care for patients in this setting has been regorafenib or trifluridine/tipiracil (TAS102) after the progression of fluoropyrimidine-based chemotherapy with

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Combination of Irinotecan, Oxaliplatin and 5-Fluorouracil as a Rechallenge Regimen for Heavily Pretreated Metastatic Colorectal Cancer Patients

Abstract: Both FOLFIRINOX and FOLFOXIRI are active and potentially feasible rechallenge treatment options for heavily pretreated patients with good performance status. With dose reduction and close monitoring for toxicity, the risk of serious adverse events can be minimised.

Cited by 13 publications

References 20 publications

Triplet Chemotherapy (FOLFOXIRI) Plus Bevacizumab Versus Doublet Chemotherapy (FOLFOX/FOLFIRI) Plus Bevacizumab in Conversion Therapy for Metastatic Colorectal Cancer: a Meta-Analysis

Triplet Chemotherapy (FOLFOXIRI) Plus Bevacizumab Versus Doublet Chemotherapy (FOLFOX/FOLFIRI) Plus Bevacizumab in Conversion Therapy for Metastatic Colorectal Cancer: a Meta-Analysis

Long non-coding RNA RAMS11 promotes metastatic colorectal cancer progression

Apatinib Monotherapy for Chemotherapy-Refractory Metastatic Colorectal Cancer: A Multi-centre, Single-Arm, Prospective Study

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