Irinotecan/Oxaliplatin/5-Fluorouracil/Leucovorin/Cetuximab As First Line Treatment In Colorectal Cancer
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ABSTRACT:
DISEASE(S): Metastatic Colorectal Cancer,Colorectal Cancer,Colorectal Neoplasms
PROVIDER: 2056279 | ecrin-mdr-crc |
REPOSITORIES: ECRIN MDR
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Project description:BackgroundWe assessed the effectiveness of cetuximab plus chronomodulated irinotecan, 5-fluorouracil (5-FU), leucovorin (FA) and oxaliplatin (L-OHP) (chrono-IFLO) administered as neoadjuvant chemotherapy to increase the resectability of colorectal liver metastases.MethodsThis was a phase II prospective trial with rate of liver metastases resection as primary end point. Forty-three patients with unresectable metastases were enroled: 9 with metastases >5 cm; 29 with multinodular (>4) disease; 1 with hilar location; 4 with extrahepatic lung disease. Treatment consisted of cetuximab at day 1 plus chronomodulated irinotecan 5-FU, FA and L-OHP for 2-6 days every 2 weeks. After the first 17 patients, doses were reduced for irinotecan to 110 mg m⁻², 5-FU to 550 mg m⁻² per day and L-OHP to 15 mg m⁻² per day.ResultsMacroscopically complete resections were performed in 26 out of 43 patients (60%) after a median of 6 (range 3-15) cycles. Partial response was noticed in 34 patients (79%). Median overall survival was 37 months (95% CI: 21-53 months), with a 2-year survival of 68% in the entire population, 80.6% in resected patients and 47.1% in unresected patients (P=0.01). Grade 3/4 diarrhoea occurred in 93% and 36% of patients before and after dose reduction.ConclusionCetuximab plus chrono-IFLO achieved 60% complete resectability of colorectal liver metastases.
| S-EPMC2990583 | biostudies-literature
Project description:Biliary tract cancers (BTC) are rare but aggressive. Due to limited anti-tumor effects of current second- and later-line treatment regimens, novel treatment options are required. Nanoliposomal irinotecan in combination with leucovorin and 5-fluorouracil (FOLFnal-IRI) achieved promising results as a second-line treatment in patients with pancreatic cancer, warranting further investigation in BTC. In the present study, a retrospective analysis of patients receiving FOLFnal-IRI after initial platinum-based chemotherapy for advanced BTC between January 2016 and August 2020 at the University Hospital Cologne (Cologne, Germany) was performed. A total of 11 patients were identified who met the inclusion criteria. A total of 4 patients (36.4%) were female and the median age was 54 years. The proportion of patients suffering from gallbladder carcinoma, intrahepatic and extrahepatic cholangiocarcinoma was 18.2, 63.6 and 9.1%, respectively. Furthermore, 7 patients (63.6%) received FOLFnal-IRI as their second-, 3 (27.3%) as third- and one (9.1%) as their fourth-line therapy. The disease control rate was 54.5% and 3 grade III toxicities were recorded. Progression-free survival and overall survival (OS) after initiation of FOLFnal-IRI was 5.1 and 12.4 months, respectively. OS after initial diagnosis was 24.7 months. FOLFnal-IRI demonstrated promising antitumor potential with an acceptable safety profile as a subsequent therapy regimen in advanced biliary tract malignancies. Further randomized controlled trials of its value as a treatment option for BTC appear justified.
| S-EPMC8764657 | biostudies-literature
Project description:In patients with advanced colorectal cancer, leucovorin, fluorouracil, and irinotecan (FOLFIRI) is considered as one of the reference first-line treatments. However, only about half of treated patients respond to this regimen, and there is no clinically useful marker that predicts response. A major clinical challenge is to identify the subset of patients who could benefit from this chemotherapy. We aimed to identify a gene expression profile in primary colon cancer tissue that could predict chemotherapy response. Patients and Methods:- Tumor colon samples from 21 patients with advanced colorectal cancer were analyzed for gene expression profiling using Human Genome GeneChip arrays U133. At the end of the first-line treatment, the best observed response, according to WHO criteria, was used to define the responders and nonresponders. Discriminatory genes were first selected by the significance analysis of microarrays algorithm and the area under the receiver operating characteristic curve. A predictor classifier was then constructed using support vector machines. Finally, leave-one-out cross validation was used to estimate the performance and the accuracy of the output class prediction rule. Results:- We determined a set of 14 predictor genes of response to FOLFIRI. Nine of nine responders (100% specificity) and 11 of 12 nonresponders (92% sensitivity) were classified correctly, for an overall accuracy of 95%. Conclusion:- After validation in an independent cohort of patients, our gene signature could be used as a decision tool to assist oncologists in selecting colorectal cancer patients who could benefit from FOLFIRI chemotherapy, both in the adjuvant and the first-line metastatic setting.
2014-10-06 | GSE62080 | GEO
Project description:Cetuximab enhances the efficacy of chemotherapy in several cancer types. This trial assessed the activity of cetuximab and chemotherapy in advanced gastric cancer.Patients with previously untreated, metastatic, gastric cancer received cetuximab 400 mg m(-2) at first infusion followed by weekly infusions of 250 mg m(-2) combined with FUFOX (oxaliplatin 50 mg m(-2), 5-FU 2000 mg m(-2), and DL-folinic acid 200 mg m(-2) d1, 8, 15 and 22 qd36). The primary endpoint was tumour response.Overall, 52 patients were enrolled. The most common grade 3/4 toxicities were diarrhoea (33%), and skin toxicity (24%). Efficacy was evaluable in 46 patients who showed a response rate of 65% (CI 95%: 50-79%) including four complete responses. Time to progression (TTP) was 7.6 months (CI 95%: 5.0-10.1 months) and overall survival (OS) was 9.5 months (CI 95%: 7.9-11.1 months). Epidermal growth factor receptor (EGFR) was detectable in 60% of tumours but showed no correlation with treatment outcome. A KRAS mutation was found in only 1 of 32 (3%) tumour samples analysed.Cetuximab plus FUFOX showed an interesting high response rate in metastatic gastric cancer. Cetuximab plus platinum-fluoropyrimidine chemotherapy is at present being investigated in a phase III randomised controlled trial.
| S-EPMC2822949 | biostudies-literature
Project description:IntroductionLiposomal irinotecan (nal-IRI) plus fluorouracil/leucovorin (5-FU/LV) has shown clinical benefit in patients with metastatic pancreatic adenocarcinoma (mPAC) who progressed on gemcitabine-based chemotherapy. However, its role in patients with mPAC previously treated with conventional irinotecan-containing chemotherapy has not been appropriately investigated.MethodsIn this retrospective analysis, patients with mPAC who received nal-IRI plus 5-FU/LV after conventional irinotecan-containing regimen between January 2017 and March 2020, were identified from two referral cancer centers in South Korea. The ratio of time to progression (TTP) with nal-IRI plus 5-FU/LV to TTP with conventional irinotecan (TTPr) was analyzed with respect to the duration and cumulative dose of conventional irinotecan treatment.ResultsIn total, 35 patients treated with nal-IRI plus 5-FU/LV after the irinotecan-containing regimen were analyzed. The median age was 58 years and 16 (46%) patients were male. The median duration of conventional irinotecan therapy was 4.6 months at a median cumulative dose of 1230 mg. The objective response rate of nal-IRI plus 5-FU/LV was 2.9%, and stable disease was achieved in 11 (31.4%) patients. During the median follow-up of 9.2 [95% confidence interval (CI): 7.8-10.5] months, the median progression-free survival (PFS) and overall survival (OS) were 2.0 (95% CI: 1.4-2.6) months and 4.4 (95% CI: 3.6-5.7) months, respectively. The 6-month PFS and OS rates were 16.3% and 37.5%, respectively. The median TTPr was 0.41 (range, 0.07-2.07), showing a negative correlation with the cumulative dose of prior irinotecan therapy (R = -0.37, p = 0.041). A tentative negative correlation between TTPr and duration of prior irinotecan therapy was observed (R = -0.35, p = 0.062). The most common grade 3-4 toxicities were neutropenia (20%) and fatigue (8.6%).ConclusionNal-IRI plus 5-FU/LV showed modest effectiveness and manageable toxicities for patients with mPAC previously treated with conventional irinotecan-containing chemotherapy. The cumulative dose of prior conventional irinotecan therapy may be inversely correlated with the effectiveness of nal-IRI plus 5-FU/LV.
| S-EPMC7983461 | biostudies-literature
Project description:To estimate progression-free survival at one year in elderly patients with RAS/BRAF wild-type unresectable mCRC and good performance status treated with FOLFIRI + panitumumab as first-line therapy.
The clinical hypothesis of this study is that the combination of panitumumab and FOLFIRI is a good treatment option in elderly patients with good performance status and RAS/BRAF wild-type unresectable mCRC. Another purpose of this clinical trial is to determine the RAS/BRAF mutation status in liquid biopsies at baseline and at the time of disease progression.
| 2243561 | ecrin-mdr-crc
Project description:Infusional fluorouracil/leucovorin (FU/LV) plus irinotecan (FOLFIRI) is one of the standard first-line options for patients with metastatic colorectal cancer (mCRC). Irinotecan is converted into 7-ethyl-10-hydroxycamptothecin (SN-38) by a carboxylsterase and metabolised through uridine diphosphate glucuronosyl transferase (UGT1A1). The UGT1A1*28 allele has been associated with the risk of developing severe toxicities. The present trial was designed to define the maximum tolerated dose according to UGT1A1 genotype. This report focuses on the results of tolerance to different escalated doses of FOLFIRI first-line of chemotherapy.Patients undergoing first-line treatment for mCRC and eligible for treatment with FOLFIRI were classified according to UGT1A1 genotype. A total of 94 patients were eligible for dose escalation of irinotecan. The starting dose of biweekly irinotecan was 180 mg m(-2) for the *1/*1, 110 mg m(-2) for the *1/*28 and 90 mg m(-2) for the *28/*28 genotypes.The dose of irinotecan was escalated to 450 mg m(-2) in patients with the *1/*1 genotype, to 390 mg m(-2) in those with the *1/*28 genotype and to 150 mg m(-2) in those with the *28/*28 genotype. Neutropenia and diarrhoea were the most common grade 3 or 4 toxicities.Our results demonstrated that the recommended dose of 180 mg m(-2) for irinotecan in FOLFIRI is considerably lower than the dose that can be tolerated for patients with the UGT1A1 *1/*1 and *1/*28 genotypes. The maximum tolerable dose (MTD) in patients with a high-risk UGT1A1 *28/*28 genotype is 30% lower than the standard dose of 180 mg m(-2).
| S-EPMC3137420 | biostudies-literature
Project description:PurposeThe primary goal of this multicenter phase III trial was to determine whether overall survival (OS) of fluorouracil (FU) -refractory patients was noninferior when treated with second-line infusional fluorouracil, leucovorin, and oxaliplatin (FOLFOX4; arm B) versus irinotecan (arm A). Cross-over to the other treatment on disease progression was mandated.Patients and methodsPatients who experienced treatment failure with one prior FU-based therapy and had not received prior irinotecan or oxaliplatin, either for metastatic disease or within 6 months of adjuvant FU therapy, were randomly assigned to arm A (irinotecan 350 or 300 mg/m(2) every 3 weeks) or arm B (FOLFOX4).ResultsA total of 491 patients were randomly assigned (arm A, n = 245; arm B, n = 246); 288 (59%) had experienced treatment failure with FU for metastatic colorectal cancer. Two hundred twenty-seven patients (46%) received protocol-mandated third-line therapy (arm A, 43%; arm B, 57%). Median survival was 13.8 months (95% CI, 12.2 to 15.0 months) for initial treatment with FOLFOX4 and 14.3 months (95% CI, 12.0 to 15.9 months) for irinotecan (P = .38; hazard ratio = 0.92; 95% CI, 0.8 to 1.1). Response rates (RR; 28% v 15.5%; P = .0009) and time to progression (TTP; 6.2 v 4.4 months; P = .0009) were significantly superior with FOLFOX4. In the nonrandom subset of patients who crossed over, RR and TTP improvements with FOLFOX4 continued into third-line treatment. Irinotecan therapy was associated with more grade 3 nausea, vomiting, diarrhea, and febrile neutropenia; FOLFOX4 was associated with more neutropenia and paresthesias.ConclusionIn patients who experienced treatment failure with front-line FU therapy, OS does not significantly differ whether second-line therapy begins with irinotecan or FOLFOX4. FOLFOX4 produces higher RR and longer TTP. Both arms had notable OS in patients who experienced treatment failure with first-line FU therapy.
| S-EPMC2698019 | biostudies-literature
Project description:PurposeIrinotecan, in combination with leucovorin/5-fluorouracil (FU) or with cisplatin, is known to be active for treating advanced gastric cancer (AGC). This pilot study evaluated a novel three-drug combination of irinotecan, leucovorin/FU and cisplatin as a first-line treatment of AGC. The primary endpoint was to assess the feasibility in anticipation of conducting a larger phase II study.Materials and methodsChemotherapy-naive AGC patients received irinotecan 150 mg/m(2) on day 1, and leucovorin 200 mg/m(2) and a 22-h infusion of FU 1000 mg/m(2) on days 1 and 2. Cisplatin 30 mg/m(2) was administered on day 2. Treatment was repeated every 2 weeks until disease progression or unacceptable toxicity.ResultsOf the 17 eligible patients, two patients had an ECOG performance status of 2 and their median age was 48 years (range: 31 to 69). A total of 117 chemotherapy cycles were delivered (median: 6, range: 1 to 12). The causes of treatment discontinuation were disease progression in 9 patients (53%), refusal (35%) and toxicity (12%). Although grade 3 or 4 neutropenia (41% of patients) was the major toxicity that required dose adjustments, only one episode of febrile neutropenia occurred. Grade 3 or 4 nausea and vomiting, diarrhea and fatigue were observed in 35%, 35% and 29% of patients, respectively. None of the patients died of toxicity during treatment. Of the 16 patients who were evaluable for response, 7 (44%) experienced a partial response.ConclusionThis novel multi-drug combination was tolerated well in patients with AGC. Based on the encouraging efficacy and tolerability, a randomized phase II study is ongoing in this disease setting.
| S-EPMC2741674 | biostudies-literature
Project description:In patients with advanced colorectal cancer, leucovorin, fluorouracil, and irinotecan (FOLFIRI) is considered as one of the reference first-line treatments. However, only about half of treated patients respond to this regimen, and there is no clinically useful marker that predicts response. A major clinical challenge is to identify the subset of patients who could benefit from this chemotherapy. We aimed to identify a gene expression profile in primary colon cancer tissue that could predict chemotherapy response. Patients and Methods:- Tumor colon samples from 21 patients with advanced colorectal cancer were analyzed for gene expression profiling using Human Genome GeneChip arrays U133. At the end of the first-line treatment, the best observed response, according to WHO criteria, was used to define the responders and nonresponders. Discriminatory genes were first selected by the significance analysis of microarrays algorithm and the area under the receiver operating characteristic curve. A predictor classifier was then constructed using support vector machines. Finally, leave-one-out cross validation was used to estimate the performance and the accuracy of the output class prediction rule. Results:- We determined a set of 14 predictor genes of response to FOLFIRI. Nine of nine responders (100% specificity) and 11 of 12 nonresponders (92% sensitivity) were classified correctly, for an overall accuracy of 95%. Conclusion:- After validation in an independent cohort of patients, our gene signature could be used as a decision tool to assist oncologists in selecting colorectal cancer patients who could benefit from FOLFIRI chemotherapy, both in the adjuvant and the first-line metastatic setting. All tissue samples were maintained at −180°C (liquid nitrogen) until RNA extraction and were weighed before homogenization. Tissue samples were then disrupted directly into a lysis buffer using Mixer Mill MM 300 (Qiagen, Valencia, CA). Total RNA was isolated from tissue lysates using the RNeasy Mini Kit (Qiagen), and additional DNAse digestion was performed on all samples during the extraction process (RNase-Free DNase Set Protocol for DNase treatment on RNeasy Mini Spin Columns; Qiagen). After each extraction, a small fraction of the total RNA preparation was taken to determine the quality of the sample and the yield of total RNA. Controls analyses were performed by UV spectroscopy and analysis of total RNA profile using the Agilent RNA 6000 Nano LabChip Kit with the Agilent 2100 Bioanalyser (Agilent Technologies, Palo Alto, CA) to determine RNA purity, quantity, and integrity.
2014-10-06 | E-GEOD-62080 | biostudies-arrayexpress