Durable complete response in a patient with metastatic left-sided colon cancer treated with 5-fluorouracil, folinic acid, and irinotecan (FOLFIRI) and panitumumab: A case report.
Ontology highlight
ABSTRACT:
SUBMITTER: Kim E
PROVIDER: S-EPMC6637324 | biostudies-literature | 2019 Jul
REPOSITORIES: biostudies-literature
Publications
Durable complete response in a patient with metastatic left-sided colon cancer treated with 5-fluorouracil, folinic acid, and irinotecan (FOLFIRI) and panitumumab: A case report.
Kim Esther E Bay Graham H GH Kim Christina A CA
Clinical case reports 20190520 7
There are rare patients with metastatic colon cancer who experience dramatic and durable responses. Primary tumor location is a prognostic and potentially predictive factor and should be taken into consideration when deciding on the optimal first-line therapy to be used in combination with chemotherapy. ...[more]
Similar Datasets
Project description:BackgroundFOLFIRI [irinotecan, folinic acid (CF), and fluorouracil] is considered a standard second-line chemotherapy regimen for patients with metastatic colorectal cancer (mCRC) who failed first-line XELOX/FOLFOX regimens. However, it remains unknown whether fluorouracil is still necessary in this case. This trial was designed to test the superiority of FOLFIRI over single-agent irinotecan as a second-line treatment for patients with mCRC.MethodsThis randomized clinical trial was conducted in five hospitals in China. From 4 November 2016 to 17 January 2020, patients aged 18 years or older with histologically confirmed unresectable mCRC and who had failed first-line XELOX/FOLFOX regimens were screened and enrolled. Patients were randomized to receive either FOLFIRI or irinotecan. The primary endpoint was progression-free survival (PFS). Secondary endpoints included overall survival (OS), objective response rate (ORR), and toxicity. Data were analyzed on an intention-to-treat basis.ResultsA total of 172 patients with mCRC were randomly treated with FOLFIRI (n = 88) or irinotecan (n = 84). The median PFS was 104 and 112 days (3.5 and 3.7 months) in the FOLFIRI and irinotecan groups, respectively [hazard ratio (HR) = 1.084, 95% confidence interval (CI) = 0.7911-1.485; p = 0.6094], and there was also no significant difference in OS and ORR between the two groups. The incidence of the following adverse events (AEs) was significantly higher in the FOLFIRI group than in the irinotecan group: any grade AEs including leucopenia (73.9% versus 55.4%), neutropenia (72.7% versus 56.6%), thrombocytopenia (31.8% versus 18.1%), jaundice (18.2% versus 7.2%), mucositis (40.9% versus 14.5%), vomiting (37.5% versus 21.7%), and fever (19.3% versus 7.2%) and grade 3-4 neutropenia (47.7% versus 21.7%).ConclusionThis is the first head-to-head trial showing that single-agent irinotecan yielded PFS, OS, and ORR similar to FOLFIRI, with a more favorable toxicity profile; therefore, it might be a more favorable standard chemotherapy regimen for mCRC patients who failed first-line XELOX/FOLFOX regimens.Trial registrationThis study is registered with ClinicalTrials.gov, number NCT02935764, registered 17 October 2016, https://clinicaltrials.gov/ct2/show/NCT02935764.
| S-EPMC8771434 | biostudies-literature
Project description:PurposeThe randomized PANAMA trial investigated the efficacy of panitumumab (Pmab) when added to maintenance therapy with fluorouracil and folinic acid (FU/FA) in patients with RAS wild-type metastatic colorectal cancer.MethodsFollowing first-line induction therapy with six cycles of FU/FA and oxaliplatin plus Pmab, responding patients (stable disease or partial or complete remission) were randomly assigned (1:1, open-label) to maintenance treatment with either FU/FA plus Pmab or FU/FA alone. The primary objective was to demonstrate superiority of progression-free survival (PFS, time from random assignment until progression or death) in favor of FU/FA plus Pmab with a hazard ratio (HR) of 0.75, a power of 80%, and a significance level of 10%. Secondary end points included overall survival, objective response rate of maintenance therapy, and toxicity. Survival end points were analyzed by the Kaplan-Meier method and compared by log-rank test and Cox regressions. Dichotomous variables were compared by Fisher's exact test; odds ratios were indicated when appropriate. The trial is registered with ClinicalTrials.gov (NCT01991873).ResultsOverall, 248 patients were randomly assigned and received maintenance therapy with either FU/FA plus Pmab (125 patients) or FU/FA alone (123 patients). At data cutoff, with 218 events (of 218 needed), PFS of maintenance therapy was significantly improved with FU/FA plus Pmab (8.8 months v 5.7 months; HR, 0.72; 80% CI, 0.60 to 0.85; P = .014). Overall survival (event rate 54%) numerically favored the FU/FA plus Pmab arm (28.7 months v 25.7 months; HR, 0.84; 95% CI, 0.60 to 1.18; P = .32). Objective response rates were 40.8% in patients receiving FU/FA plus Pmab versus 26.0% in patients receiving FU/FA alone (odds ratio, 1.96; 95% CI, 1.14 to 3.36; P = .02). The most frequent Common Terminology Criteria for Adverse Event grade ≥ 3 event during maintenance therapy was skin rash (7.2%).ConclusionIn RAS wild-type metastatic colorectal cancer, maintenance therapy with FU/FA plus Pmab induced a significantly superior PFS compared with FU/FA alone. If active maintenance therapy is aspired following induction therapy with FU/FA and oxaliplatin plus Pmab, FU/FA plus Pmab appears to be the most favorable option.
| S-EPMC8683209 | biostudies-literature
Project description:BackgroundThe RAISE phase III clinical trial demonstrated that ramucirumab + FOLFIRI improved overall survival (OS) [hazard ratio (HR) = 0.844, P = 0.0219] and progression-free survival (PFS) (HR = 0.793, P < 0.0005) compared with placebo + FOLFIRI for second-line metastatic colorectal carcinoma (mCRC) patients previously treated with first-line bevacizumab, oxaliplatin, and a fluoropyrimidine. Since some patient or disease characteristics could be associated with differential efficacy or safety, prespecified subgroup analyses were undertaken. This report focuses on three of the most relevant ones: KRAS status (wild-type versus mutant), age (<65 versus ≥65 years), and time to progression (TTP) on first-line therapy (<6 versus ≥6 months).Patients and methodsOS and PFS were evaluated by the Kaplan-Meier analysis, with HR determined by the Cox proportional hazards model. Treatment-by-subgroup interaction was tested to determine whether treatment effect was consistent between subgroup pairs.ResultsPatients with both wild-type and mutant KRAS benefited from ramucirumab + FOLFIRI treatment over placebo + FOLFIRI (interaction P = 0.526); although numerically, wild-type KRAS patients benefited more (wild-type KRAS: median OS = 14.4 versus 11.9 months, HR = 0.82, P = 0.049; mutant KRAS: median OS = 12.7 versus 11.3 months, HR = 0.89, P = 0.263). Patients with both longer and shorter first-line TTP benefited from ramucirumab (interaction P = 0.9434), although TTP <6 months was associated with poorer OS (TTP ≥6 months: median OS = 14.3 versus 12.5 months, HR = 0.86, P = 0.061; TTP <6 months: median OS = 10.4 versus 8.0 months, HR = 0.86, P = 0.276). The subgroups of patients ≥65 versus <65 years also derived a similar ramucirumab survival benefit (interaction P = 0.9521) (≥65 years: median OS = 13.8 versus 11.7 months, HR = 0.85, P = 0.156; <65 years: median OS = 13.1 versus 11.9 months, HR = 0.86, P = 0.098). The safety profile of ramucirumab + FOLFIRI was similar across subgroups.ConclusionsThese analyses revealed similar efficacy and safety among patient subgroups with differing KRAS mutation status, longer or shorter first-line TTP, and age. Ramucirumab is a beneficial addition to second-line FOLFIRI treatment for a wide range of patients with mCRC.Trial registrationClinicalTrials.gov, NCT01183780.
| S-EPMC5091322 | biostudies-literature
Project description:BackgroundTherapeutic options are limited for advanced, metastatic biliary tract cancer. The pivotal NAPOLI-1 trial demonstrated the superior clinical benefit of nanoliposomal irinotecan (Nal-IRI) in gemcitabine-pretreated patients with metastatic pancreatic ductal adenocarcinoma; however, the antitumor activity of Nal-IRI in biliary tract cancer is unknown. This is the first report describing the efficacy of Nal-IRI in biliary tract cancer.MethodsIn this multicenter retrospective cohort analysis, we identified patients with metastatic biliary tract adenocarcinoma who were treated with Nal-IRI in combination with 5-fluorouracil and folinic acid following tumor progression under standard therapy at one of the study centers between May 2016 and January 2019. We assessed disease control rate (DCR), progression-free survival (PFS), and overall survival (OS).ResultsThere were 14 patients; the median age at the time of diagnosis and the median age at the initiation of Nal-IRI were 59.3 and 60.0 years, respectively. Nal-IRI in combination with 5-fluorouracil and folinic acid was administered as second-, third-, fourth-, and fifth-line treatment in 6 (43%), 5 (36%), 2 (14%), and 1 (7%) patient with metastatic disease, respectively. The objective DCR with Nal-IRI was 50% (7/14 patients). Six patients (43%) had partial response, and one patient (7%) had stable disease. Progressive disease was observed in seven patients. The median PFS and median OS following Nal-IRI initiation were 10.6 and 24.1 months, respectively.ConclusionsThis retrospective analysis provides the first evidence that Nal-IRI might exhibit a clinical meaningful antitumor activity in metastatic biliary tract cancer.
| S-EPMC7338813 | biostudies-literature
Project description:5-Fluorouracil (5-FU)-based adjuvant chemotherapy (ACT) is widely used for the treatment of colon cancer. Colon cancers with different primary tumor locations are clinically and molecularly distinct, implied through their response to 5-FU-based ACT. In this work, using 69 and 133 samples of patients with stage II-III right-sided and left-sided colon cancer (RCC and LCC) treated with post-surgery 5-FU-based ACT, we preselected gene pairs whose relative expression orderings were significantly correlated with the disease-free survival of patients by univariate Cox proportional hazards model. Then, from the identified prognostic-related gene pairs, a forward-stepwise selection algorithm was formulated to search for an optimal subset of gene pairs that resulted in the highest concordance index, referred to as the gene pair signature (GPS). We identified prognostic signatures, 3-GPS and 5-GPS, for predicting response to 5-FU-based ACT of patients with RCC and LCC, respectively, which were validated in independent datasets of GSE14333 and GSE72970. With the aid of the signatures, the transcriptional and genomic characteristics between the predicted responders and non-responders were explored. Notably, both in RCC and LCC, the predicted responders to 5-FU-based ACT were characterized by hypermutation, whereas the predicted non-responders were characterized by frequent copy number alternations. Finally, in comparison with the established relative expression ordering-based signature, which was developed without considering the differences between RCC and LCC, the newly proposed signatures had a better predictive performance. In conclusion, 3-GPS or 5-GPS can robustly predict response to 5-FU-based ACT for patients with RCC or LCC, respectively, in an individual level.
| S-EPMC5989868 | biostudies-literature
Project description:Background: Aflibercept and fluorouracil, leucovorin, irinotecan (FOLFIRI) is commonly used as a second-line treatment for metastatic colorectal cancer (CRC). However, the biomarkers to guide the choice of this regimen from among treatment options remain unclear. Patients and Methods: We performed exploratory analyses to validate potential prognostic factors for patients receiving aflibercept plus FOLFIRI as a second-line systemic treatment for metastatic CRC between January 2015 and July 2019. Patient characteristics, histopathologic data, laboratory and radiologic data, and treatment outcomes were collected and reviewed. Results: Included were 52 patients: 50 (96.2%) received bevacizumab plus fluorouracil, leucovorin, oxaliplatin (FOLFOX) as prior first-line treatment. Among the 52 patients receiving aflibercept and FOLFIRI, four complete responses and 21 partial responses were observed in analyzed patients for an overall response rate of 48.1%. Median progression-free survival (PFS) was 7.0 months and overall survival (OS) was 16.8 months. Response to first-line treatment (median PFS, 8.0 versus 4.2 months), left-side location of primary tumor (7.9 versus 4.9 months), low baseline CEA level (8.0 versus 5.9 months), and no RAS/RAF mutation (9.9 versus 6.4 months) were remained significant prognostic factors for PFS in the multivariate backward stepwise Cox regression model, and the latter three factors were also significantly related to OS. Conclusions: Significant prognostic factors for PFS with aflibercept plus FOLFIRI as second-line therapy were extracted and validated in the multivariate OS model. These findings could provide useful information for selecting patients for aflibercept plus FOLFIRI as second-line therapy.
| S-EPMC7739009 | biostudies-literature
Project description:BackgroundClinical trials in metastatic colorectal cancer (mCRC) are usually conducted irrespective of sex. Sex-associated differences relating to safety and efficacy in the treatment of mCRC, however, are gaining interest.MethodsPanaMa investigated the efficacy of panitumumab (Pmab) plus fluorouracil and folinic acid (FU/FA) versus FU/FA alone after induction therapy with six cycles of FU/FA and oxaliplatin plus Pmab in patients with RAS wild-type mCRC. In this post hoc analysis, the study population was stratified for sex. Evaluated efficacy endpoints during maintenance treatment were progression-free survival (PFS, primary endpoint of the trial), overall survival (OS) and objective response rate during maintenance therapy. Safety endpoints were rates of any grade and grade 3/4 adverse events during maintenance therapy.ResultsIn total, 165 male and 83 female patients were randomized and treated. Male and female patients showed numerically better objective response rates with Pmab, without reaching statistical significance. Male patients derived a significant benefit from the addition of Pmab to maintenance treatment with regard to PFS [hazard ratio (HR) 0.63; 95% confidence interval (CI) 0.45-0.88; P = 0.006] that was not observed in female patients (HR 0.85; 95% CI 0.53-1.35; P = 0.491). The better PFS for male patients treated with Pmab did not translate into improved OS (HR 0.85; 95% CI 0.55-1.30; P = 0.452). Female patients showed numerically improved OS when treated with Pmab. There was no difference in the total of grade ≥3 adverse events during maintenance regarding sex (P = 0.791). Female patients, however, had a higher rate of any grade nausea, diarrhea and stomatitis.ConclusionsIn the PanaMa trial, the addition of Pmab to maintenance treatment of RAS wild-type mCRC with FU/FA improved the outcome in terms of the primary endpoint (PFS) particularly in male patients. Female patients did not show the same benefit while experiencing higher rates of adverse events. Our results support the development of sex-specific protocols.
| S-EPMC10507735 | biostudies-literature
Project description:PurposeTo verify whether the intensification of the upfront chemotherapy backbone with a modified schedule of modified fluorouracil, leucovorin, oxaliplatin, and irinotecan (mFOLFOXIRI) increases the activity of fluorouracil, leucovorin, and oxaliplatin when both regimens are combined with panitumumab as initial treatment for RAS and BRAF wild-type (wt) metastatic colorectal cancer (mCRC).MethodsTRIPLETE was a prospective, open-label, phase III trial in which previously untreated patients with unresectable RAS and BRAF wt mCRC were randomly assigned 1:1 to modified FOLFOX/panitumumab (control group) or mFOLFOXIRI/panitumumab (experimental group) up to 12 cycles, followed by fluorouracil/-leucovorin/panitumumab until disease progression. The primary end point was objective response rate (ORR) according to RECIST 1.1. Hypothesizing an ORR of 60% in the control group, 432 cases provided 90% power to a two-sided chi-square test for heterogeneity with a two-sided alpha error of .05 to detect ≥ 15% differences between arms (ClinicalTrials.gov identifier: NCT03231722).ResultsFrom September 2017 to September 2021, 435 patients were enrolled (control group/experimental group: 217/218) in 57 Italian sites. One hundred sixty (73%) patients treated with mFOLFOXIRI plus panitumumab and 165 (76%) patients treated with modified FOLFOX plus panitumumab achieved RECIST response (odds ratio 0.87, 95% CI, 0.56 to 1.34, P = .526). No differences in early tumor shrinkage rate (57%/58%, P = .878) and deepness of response (median: 48%/47%, P = .845) were reported, nor in R0 resection rate (25%/29%, P = .317). No significant difference between arms was reported in terms of progression-free survival (median progression-free survival: 12.7 in the experimental group v 12.3 months in the control group, hazard ratio: 0.88, 95% CI, 0.70 to 1.11, P = .277).ConclusionThe intensification of the upfront chemotherapy backbone in combination with panitumumab does not provide additional benefit in terms of treatment activity at the price of increased gastrointestinal toxicity in patients with RAS and BRAF wt mCRC.
| S-EPMC9426812 | biostudies-literature
Project description:PurposeGC1118 is a novel antibody targeting epidermal growth factor receptor (EGFR) with enhanced blocking activity against both low- and high-affinity EGFR ligands. A phase 1b/2a study was conducted to determine a recommended phase 2 dose (RP2D) of GC1118 in combination with 5-fluorouracil, leucovorin, and irinotecan (FOLFIRI) (phase 1b) and to assess the safety and efficacy of GC1118 plus FOLFIRI as a second-line therapy for recurrent/metastatic colorectal cancer (CRC) (phase 2a).Materials and methodsPhase 1b was designed as a standard 3+3 dose-escalation study with a starting dose of GC1118 (3 mg/kg/week) in combination with biweekly FOLFIRI (irinotecan 180 mg/m2; leucovorin 400 mg/m2; 5-fluorouracil 400 mg/m2 bolus and 2,400 mg/m2 infusion over 46 hours) in patients with solid tumors refractory to standard treatments. The subsequent phase 2a part was conducted with objective response rate (ORR) as a primary endpoint. Patients with KRAS/NRAS/BRAF wild-type, EGFR-positive, recurrent/metastatic CRC resistant to the first-line treatment were enrolled in the phase 2a study.ResultsRP2D of GC1118 was determined to be 3 mg/kg/wk in the phase 1b study (n=7). Common adverse drug reactions (ADRs) observed in the phase 2a study (n=24) were acneiform rash (95.8%), dry skin (66.7%), paronychia (58.3%), and stomatitis (50.0%). The most common ADR of ≥ grade 3 was neutropenia (33.3%). ORR was 42.5% (95% confidence interval [CI], 23.5 to 62.0), and median progression-free survival was 6.7 months (95% CI, 4.0-8.0).ConclusionGC1118 administered weekly at 3 mg/kg in combination with FOLFIRI appears as an effective and safe treatment option in recurrent/metastatic CRC.
| S-EPMC11016642 | biostudies-literature
Project description:Tumor sidedness has emerged as an important prognostic and predictive factor in the treatment of colorectal cancer. Recent studies demonstrate that patients with advanced right-sided colon cancers have a worse prognosis than those with left-sided colon or rectal cancers, and these patient subgroups respond differently to biological therapies. Historically, management of patients with metastatic colon and rectal cancers has been similar, and colon and rectal cancer patients have been grouped together in large clinical trials. Clearly, the differences in molecular biology among right-sided colon, left-sided colon, and rectal cancers should be further studied in order to account for disparities in clinical outcomes. We profiled 10,570 colorectal tumors (of which 2,413 were identified as arising from the left colon, right colon, or rectum) using next-generation sequencing, immunohistochemistry, chromogenic in-situ hybridization, and fragment analysis (Caris Life Sciences, Phoenix, AZ). Right-sided colon cancers had higher rates of microsatellite instability, more frequent aberrant activation of the EGFR pathway including higher BRAF and PIK3CA mutation rates, and increased mutational burden compared to left-sided colon and rectal cancers. Rectal cancers had higher rates of TOPO1 expression and Her2/neu amplification compared to both left- and right-sided colon cancers. Molecular variations among right-sided colon, left-sided colon, and rectal tumors may contribute to differences in clinical behavior. The site of tumor origin (left colon, right colon, or rectum) should certainly be considered when selecting treatment regimens and stratifying patients for future clinical trials.
| S-EPMC5689690 | biostudies-other