RESUMO
BACKGROUND: The key endpoints for the assessment of the effect of maintenance therapy for metastatic colorectal cancer (mCRC) are survival and quality-of-life outcomes. We aimed to compare dermatology-related quality of life (DRQOL) in patients with RAS wild-type (wt) mCRC treated with fluorouracil and folinic acid (FU/FA) + panitumumab (Pmab) versus FU/FA alone as maintenance therapy after folinic acid, fluorouracil and oxaliplatin + Pmab induction. PATIENTS AND METHODS: The phase II randomized PanaMa (AIO KRK 0212; NCT01991873) trial included 387 patients at 70 community/academic sites in Germany. For this prespecified secondary analysis, DRQOL outcomes were assessed using the Functional Assessment of Cancer Therapy-epidermal growth factor receptor inhibitor (FACT-EGFRI), Dermatology Life Quality Index (DLQI), and Skindex-16 questionnaires at every second cycle of therapy until disease progression/death. RESULTS: At least one DRQOL questionnaire was completed by a total of 310/377 (82%) patients who received induction therapy, and by 216/248 (87%) patients who were randomized and received maintenance therapy. Patients who experienced skin toxicity according to the National Cancer Institute (NCI)-Common Terminology Criteria for Adverse Events (CTCAE) during induction therapy had significantly worse DRQOL according to all three measures, compared to those who did not [i.e. Skindex-16, mean difference at cycle 2 -12.87; 95% confidence interval (CI) -20.01 to -5.73; P < 0.001]. During maintenance therapy, significantly improved recovery was observed in all DRQOL measures for patients receiving FU/FA, compared to those receiving additional Pmab (i.e. Skindex-16, mean difference at cycle 6 -16.53; 95% CI -22.68 to -10.38; P < 0.001). CONCLUSIONS: In this secondary analysis of a phase II randomized clinical trial, patient-reported DRQOL outcomes correlated with skin toxicity according to NCI-CTCAE during induction therapy. Maintenance therapy with FU/FA + Pmab was associated with deteriorated DRQOL versus FU/FA alone in patients with RAS wt mCRC.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica , Neoplasias Colorretais , Fluoruracila , Leucovorina , Panitumumabe , Qualidade de Vida , Humanos , Fluoruracila/uso terapêutico , Fluoruracila/farmacologia , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/patologia , Masculino , Feminino , Leucovorina/uso terapêutico , Leucovorina/farmacologia , Leucovorina/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Panitumumabe/uso terapêutico , Panitumumabe/farmacologia , Pessoa de Meia-Idade , Idoso , Adulto , Compostos Organoplatínicos/uso terapêutico , Compostos Organoplatínicos/farmacologiaRESUMO
BACKGROUND: This retrospective study aimed to determine the optimal metronomic chemotherapy duration (MTCD) as adjuvant therapy for patients with locally advanced nasopharyngeal carcinoma (LANPC). METHODS: This study involved LANPC patients treated with metronomic chemotherapy (MTC) using a 5-FU prodrug (S1, capecitabine, or tegafur) from May 2013 to September 2020. The optimal MTCD threshold was established using X-tile Bioinformatics software. The overall survival (OS), progression-free survival (PFS), distant metastasis-free survival (DMFS), and locoregional relapse-free survival (LRRFS) were compared between short-term and long-term groups using propensity score matching (PSM). RESULTS: A total of 546 patients were analyzed. MTCD was an independent prognostic factor for OS, PFS, and DMFS (all P < 0.05). Patients were categorized into long-term (>3 months) and short-term (≤3 months) MTCD groups. After a median follow-up of 48 months, significant differences were observed in 4-year OS (97.0 % vs. 87.1 %; P < 0.01), PFS (84.6 % vs. 70.9 %; P < 0.01), DMFS (87.3 % vs. 78.8 %; P < 0.01), and LRRFS (95.3 % vs. 87.4 %; P < 0.01) between the long-term and short-term groups. In the PSM-matched cohort of 196 patients per group, the long-term group demonstrated superior 4-year OS and LRRFS (97.3 % vs. 87.1 %, P < 0.01; 95.2 % vs. 90.0 %, P < 0.05). No significant differences in acute toxicities were observed between the groups (P > 0.05). CONCLUSION: Extended MTC with a 5-FU prodrug (>3 months) may benefit NPC patients. Further prospective studies are needed to validate these findings.
Assuntos
Administração Metronômica , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas , Pontuação de Propensão , Humanos , Masculino , Carcinoma Nasofaríngeo/tratamento farmacológico , Carcinoma Nasofaríngeo/mortalidade , Carcinoma Nasofaríngeo/patologia , Feminino , Pessoa de Meia-Idade , Quimioterapia Adjuvante/métodos , Estudos Retrospectivos , Neoplasias Nasofaríngeas/tratamento farmacológico , Neoplasias Nasofaríngeas/patologia , Neoplasias Nasofaríngeas/mortalidade , Adulto , Idoso , Capecitabina/administração & dosagem , Capecitabina/uso terapêutico , Fluoruracila/administração & dosagem , Fluoruracila/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêuticoRESUMO
BACKGROUND: Neoadjuvant radiation and oxaliplatin-based systemic therapy (total neoadjuvant therapy-TNT) have been shown to increase response and organ-preservation rates in localized rectal cancer. However, trials have been heterogeneous regarding treatment protocols and few have used a watch-and-wait (WW) approach for complete responders. This trial evaluates if conventional long-term chemoradiation followed by consolidation of FOLFIRINOX increases complete response rates and the number of patients managed by WW. METHODS: This was a pragmatic randomized phase II trial conducted in 2 Cancer Centers in Brazil that included patients with T3+ or N+ rectal adenocarcinoma. After completing a long-course 54 Gy chemoradiation with capecitabine patients were randomized 1:1 to 4 cycles of mFOLFIRINOX (Oxaliplatin 85, irinotecan 150, 5-FU 2400)-TNT-arm-or to the control arm, that did not include further neoadjuvant treatment. All patients were re-staged with dedicated pelvic magnetic resonance imaging and sigmoidoscopy 12 weeks after the end of radiation. Patients with a clinical complete response were followed using a WW protocol. The primary endpoint was complete response: clinical complete response (cCR) or pathological response (pCR). RESULTS: Between April 2021 and June 2023, 55 patients were randomized to TNT and 53 to the control arm. Tumors were 74% stage 3, median distance from the anal verge was 6 cm, 63% had an at-risk circumferential margin, and 33% an involved sphincter. The rates of cCR + pCR were (31%) for TNT versus (17%) for controls (odds ratio 2.19, CI 95% 0.8-6.22 P = .091) and rates of WW were 16% and 9% (P = ns). Median follow-up was 8.1 months and recurrence rates were 16% versus 21% for TNT and controls (P = ns). CONCLUSIONS: TNT with consolidation FOLFIRINOX is feasible and has high response rates, consistent with the current literature for TNT. This trial was supported by a grant from the Brazilian Government (PROADI-SUS - NUP 25000.164382/2020-81).
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica , Fluoruracila , Irinotecano , Leucovorina , Terapia Neoadjuvante , Estadiamento de Neoplasias , Oxaliplatina , Neoplasias Retais , Humanos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Retais/terapia , Neoplasias Retais/patologia , Terapia Neoadjuvante/métodos , Oxaliplatina/uso terapêutico , Oxaliplatina/administração & dosagem , Pessoa de Meia-Idade , Masculino , Fluoruracila/administração & dosagem , Fluoruracila/uso terapêutico , Feminino , Idoso , Brasil , Irinotecano/uso terapêutico , Irinotecano/administração & dosagem , Leucovorina/uso terapêutico , Leucovorina/administração & dosagem , Adulto , Quimiorradioterapia/métodos , Adenocarcinoma/terapia , Adenocarcinoma/patologia , Conduta Expectante/estatística & dados numéricos , Resultado do Tratamento , Quimiorradioterapia Adjuvante/métodos , Quimiorradioterapia Adjuvante/estatística & dados numéricos , Capecitabina/administração & dosagem , Capecitabina/uso terapêutico , SeguimentosRESUMO
BACKGROUND: 5-Fluorouracil (5-FU) is a first-line drug to treat cutaneous field cancerization (CFC). There are few clinical trials with topical colchicine (COL). OBJECTIVE: To evaluate the effectiveness of 0.5% COL cream versus 5% 5-FU cream in the treatment of CFC. METHOD: This was a randomized, open, self-controlled clinical trial. Forty-five patients (90 forearms), with three to ten actinic keratoses (AK) on each forearm, used 0.5% COL cream 2×/day for seven days on one forearm, and 5% 5-FU cream 2× /day, for 21 days, on the other forearm. The dosages were defined based on previous clinical trials for each drug. Adverse effects were evaluated after 14 days and outcomes after 90 days of inclusion. The primary outcome was complete AK clearance and the secondary outcomes were: partial clearance (≥50%), reduction in AK count, assessment of the Forearm Photoaging Scale (FPS), AK Severity Score (AKSS), and adverse effects. RESULTS: After 90 days, there was complete clearance of AK in 37% (95% CI 24%-49%) and partial clearance in 85% (95% CI 76%-93%) of the forearms treated with 5-FU,versus 17% (95% CI 7%-27%) and 78% (95% CI 66%-88%) for COL (p > 0.07). There was a percentage reduction of 75% in the AK count of the forearms treated with 5-FU (95% CI 66%-83%) and 64% in those treated with COL (95% CI 55%-72%). Regarding FPS and AKSS, there was improvement in both groups, with no difference regarding FPS (p = 0.654), and 5-FU superiority for AKSS (p = 0.012). STUDY LIMITATIONS: Single-center study. CONCLUSIONS: 5-FU and COL are effective for treating CFC, with neither showing superiority regarding the reduction in AK counts.
Assuntos
Colchicina , Fluoruracila , Ceratose Actínica , Creme para a Pele , Humanos , Fluoruracila/administração & dosagem , Fluoruracila/efeitos adversos , Fluoruracila/uso terapêutico , Colchicina/administração & dosagem , Colchicina/efeitos adversos , Colchicina/uso terapêutico , Ceratose Actínica/tratamento farmacológico , Masculino , Feminino , Idoso , Resultado do Tratamento , Pessoa de Meia-Idade , Creme para a Pele/administração & dosagem , Idoso de 80 Anos ou mais , Administração Cutânea , Antimetabólitos Antineoplásicos/administração & dosagem , Antimetabólitos Antineoplásicos/efeitos adversos , Antimetabólitos Antineoplásicos/uso terapêutico , Índice de Gravidade de Doença , Neoplasias Cutâneas/tratamento farmacológico , Neoplasias Cutâneas/patologia , Fatores de TempoRESUMO
INTRODUCCIÓN: Cuadro clínico: El cáncer colorrectal (CCR) es el 4° cáncer más frecuente y es la 3° causa de muerte por cáncer a nivel mundial. En Perú, el CCR es el 5° cáncer más frecuente y la 6° causa de muerte por cáncer a nivel nacional. El 20 % es diagnosticado en etapa metastásica. De los pacientes con CCR en etapa metastásica hasta un 30 % tienen metástasis hepática. A nivel molecular, la presencia de mutaciones RAS se reporta entre el 12 % y 75 % (las proteínas RAS participan en la activación del EGFR que conduce a la tumorigénesis de colon) y a nivel histológico, las características del tumor primario del lado izquierdo son distintas a la del lado opuesto. Sobre la carga de enfermedad, los reportes nacionales informan que el cáncer colorrectal genera 19,955 años de vida saludables perdidos (AVISA). Con respecto al tratamiento, siendo el CCR metastásico (CCRM) una enfermedad incurable, el objetivo del tratamiento es prolongar la vida, maximizando la calidad de vida y seguridad del paciente. Dentro de las opciones de terapias sistemáticas, la quimioterapia sigue siendo una de las alternativas recomendadas, entre ellas el esquema denominado FOLFOX (compuesto por 5-fluorouracilo con leucovorina y oxaliplatino). Tecnología sanitária: El cetuximab un anticuerpo monoclonal quimérico de tipo IgG1, contra el EGFR. En Perú, el cetuximab cuenta con registro sanitario (N°BE00609), otorgado por la
Assuntos
Humanos , Neoplasias Colorretais/tratamento farmacológico , Leucovorina/uso terapêutico , Cetuximab/uso terapêutico , Fluoruracila/uso terapêutico , Oxaliplatina/uso terapêutico , Metástase Neoplásica/tratamento farmacológico , Avaliação em Saúde/economia , Eficácia , Análise Custo-Benefício/economiaRESUMO
BACKGROUND: The optimal chemotherapy backbone for HER2-negative advanced esophagogastric cancer, either in combination with targeted therapies or as a comparator in clinical trials, is uncertain. The subtle yet crucial differences in platinum-based regimens' safety and synergy with combination treatments need consideration. METHODS: We analyzed cases from the AGAMENON-SEOM Spanish registry of HER2-negative advanced esophagogastric adenocarcinoma treated with platinum and fluoropyrimidine from 2008 to 2021. This study focused exclusively on patients receiving one of the four regimens: FOLFOX (5-FU and oxaliplatin), CAPOX (capecitabine and oxaliplatin), CP (capecitabine and cisplatin) and FP (5-FU and cisplatin). The aim was to determine the most effective and tolerable platinum and fluoropyrimidine-based chemotherapy regimen and to identify any prognostic factors. RESULTS: Among 1293 patients, 36% received either FOLFOX (n = 468) or CAPOX (n = 466), 20% CP (n = 252), and 8% FP (n = 107). FOLFOX significantly increased PFS (progression free survival) compared to CP, with a hazard ratio of 0.73 (95% CI 0.58-0.92, p = 0.009). The duration of treatment was similar across all groups. Survival outcomes among regimens were similar, but analysis revealed worse ECOG-PS (Eastern Cooperative Oncology Group-Performance Status), > 2 metastatic sites, bone metastases, hypoalbuminemia, higher NLR (neutrophil-to-lymphocyte ratio), and CP regimen as predictors of poor PFS. Fatigue was common in all treatments, with the highest incidence in FOLFOX (77%), followed by FP (72%), CAPOX (68%), and CP (60%). Other notable toxicities included neuropathy (FOLFOX 69%, CAPOX 62%), neutropenia (FOLFOX 52%, FP 55%), hand-foot syndrome in CP (46%), and thromboembolic events (FP 12%, CP 11%). CONCLUSIONS: FOLFOX shown better PFS than CP. Adverse effects varied: neuropathy was more common with oxaliplatin, while thromboembolism was more frequent with cisplatin.
Assuntos
Adenocarcinoma , Protocolos de Quimioterapia Combinada Antineoplásica , Capecitabina , Cisplatino , Neoplasias Esofágicas , Fluoruracila , Leucovorina , Oxaliplatina , Receptor ErbB-2 , Sistema de Registros , Neoplasias Gástricas , Humanos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/patologia , Feminino , Masculino , Pessoa de Meia-Idade , Idoso , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/patologia , Fluoruracila/uso terapêutico , Fluoruracila/administração & dosagem , Neoplasias Esofágicas/tratamento farmacológico , Neoplasias Esofágicas/patologia , Capecitabina/uso terapêutico , Capecitabina/administração & dosagem , Receptor ErbB-2/metabolismo , Leucovorina/uso terapêutico , Leucovorina/administração & dosagem , Leucovorina/efeitos adversos , Oxaliplatina/uso terapêutico , Oxaliplatina/administração & dosagem , Cisplatino/uso terapêutico , Cisplatino/administração & dosagem , Adulto , Compostos Organoplatínicos/uso terapêutico , Compostos Organoplatínicos/administração & dosagem , Intervalo Livre de Progressão , Junção Esofagogástrica/patologia , Idoso de 80 Anos ou mais , EspanhaRESUMO
PURPOSE: A combination of fluorouracil, leucovorin, and oxaliplatin (FOLFOX) is the standard for adjuvant therapy of resected early-stage colon cancer (CC). Oxaliplatin leads to lasting and disabling neurotoxicity. Reserving the regimen for patients who benefit from oxaliplatin would maximize efficacy and minimize unnecessary adverse side effects. METHODS: We trained a new machine learning model, referred to as the colon oxaliplatin signature (COLOXIS) model, for predicting response to oxaliplatin-containing regimens. We examined whether COLOXIS was predictive of oxaliplatin benefits in the CC adjuvant setting among 1,065 patients treated with 5-fluorouracil plus leucovorin (FULV; n = 421) or FULV + oxaliplatin (FOLFOX; n = 644) from NSABP C-07 and C-08 phase III trials. The COLOXIS model dichotomizes patients into COLOXIS+ (oxaliplatin responder) and COLOXIS- (nonresponder) groups. Eight-year recurrence-free survival was used to evaluate oxaliplatin benefits within each of the groups, and the predictive value of the COLOXIS model was assessed using the P value associated with the interaction term (int P) between the model prediction and the treatment effect. RESULTS: Among 1,065 patients, 526 were predicted as COLOXIS+ and 539 as COLOXIS-. The COLOXIS+ prediction was associated with prognosis for FULV-treated patients (hazard ratio [HR], 1.52 [95% CI, 1.07 to 2.15]; P = .017). The model was predictive of oxaliplatin benefits: COLOXIS+ patients benefited from oxaliplatin (HR, 0.65 [95% CI, 0.48 to 0.89]; P = .0065; int P = .03), but COLOXIS- patients did not (COLOXIS- HR, 1.08 [95% CI, 0.77 to 1.52]; P = .65). CONCLUSION: The COLOXIS model is predictive of oxaliplatin benefits in the CC adjuvant setting. The results provide evidence supporting a change in CC adjuvant therapy: reserve oxaliplatin only for COLOXIS+ patients, but further investigation is warranted.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica , Neoplasias do Colo , Fluoruracila , Leucovorina , Aprendizado de Máquina , Oxaliplatina , Humanos , Neoplasias do Colo/tratamento farmacológico , Neoplasias do Colo/patologia , Neoplasias do Colo/mortalidade , Oxaliplatina/uso terapêutico , Oxaliplatina/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Fluoruracila/uso terapêutico , Fluoruracila/administração & dosagem , Leucovorina/uso terapêutico , Leucovorina/administração & dosagem , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Compostos Organoplatínicos/uso terapêutico , Compostos Organoplatínicos/administração & dosagem , Quimioterapia Adjuvante , Adulto , Ensaios Clínicos Fase III como Assunto , Estadiamento de NeoplasiasRESUMO
Colorectal cancer (CRC) is the third most common and deadliest cancer globally. Regimens using 5-fluorouracil (5FU) and Oxaliplatin (OXA) are the first-line treatment for CRC, but tumor recurrence is frequent. It is plausible to hypothesize that differential cellular responses are triggered after treatments depending on the genetic background of CRC cells and that the rational modulation of cell tolerance mechanisms like autophagy may reduce the regrowth of CRC cells. This study proposes investigating the cellular mechanisms triggered by CRC cells exposed to 5FU and OXA using a preclinical experimental design mimicking one cycle of the clinical regimen (i.e., 48 h of treatment repeated every 2 weeks). To test this, we treated CRC human cell lines HCT116 and HT29 with the 5FU and OXA, combined or not, for 48 h, followed by analysis for two additional weeks. Compared to single-drug treatments, the co-treatment reduced tumor cell regrowth, clonogenicity and stemness, phenotypes associated with tumor aggressiveness and poor prognosis in clinics. This effect was exerted by the induction of apoptosis and senescence only in the co-treatment. However, a week after treatment, cells that tolerated the treatment had high levels of autophagy features and restored the proliferative phenotype, resembling tumor recurrence. The pharmacologic suppression of early autophagy during its peak of occurrence, but not concomitant with chemotherapeutics, strongly reduced cell regrowth. Overall, our experimental model provides new insights into the cellular mechanisms that underlie the response and tolerance of CRC cells to 5FU and OXA, suggesting optimized, time-specific autophagy inhibition as a new avenue for improving the efficacy of current treatments.
Assuntos
Neoplasias Colorretais , Humanos , Oxaliplatina/farmacologia , Oxaliplatina/uso terapêutico , Neoplasias Colorretais/genética , Recidiva Local de Neoplasia , Células HT29 , Fluoruracila/farmacologia , Fluoruracila/uso terapêutico , Apoptose , Autofagia , Linhagem Celular Tumoral , Resistencia a Medicamentos Antineoplásicos/genéticaRESUMO
PURPOSE: We evaluated additional mutations in RAS wild-type (WT) metastatic colorectal cancer (mCRC) as prognostic and predictive biomarkers for the efficacy of added panitumumab to a 5-fluorouracil plus folinic acid (FU/FA) maintenance as pre-specified analysis of the randomized PanaMa trial. PATIENTS AND METHODS: Mutations (MUT) were identified using targeted next-generation sequencing (NGS; Illumina Cancer Hotspot Panel v2) and IHC. RAS/BRAF V600E/PIK3CA/AKT1/ALK1/ERBB2/PTEN MUT and HER2/neu overexpressions were negatively hyperselected and correlated with median progression-free survival (PFS) and overall survival (OS) since start of maintenance treatment, and objective response rates (ORR). Univariate/multivariate Cox regression estimated hazard ratios (HR) and 95% confidence intervals (CI). RESULTS: 202 of 248 patients (81.5%) of the full analysis set (FAS) had available NGS data: hyperselection WT, 162 (80.2%); MUT, 40 (19.8%). From start of maintenance therapy, hyperselection WT tumors were associated with longer median PFS as compared with hyperselection MUT mCRC (7.5 vs. 5.4 months; HR, 0.75; 95% CI, 0.52-1.07; P = 0.11), OS (28.7 vs. 22.2 months; HR, 0.53; 95% CI, 0.36-0.77; P = 0.001), and higher ORR (35.8% vs. 25.0%, P = 0.26). The addition of panitumumab to maintenance was associated with significant benefit in hyperselection WT tumors for PFS (9.2 vs. 6.0 months; HR, 0.66; 95% CI, 0.47-0.93; P = 0.02) and numerically also for OS (36.9 vs. 24.9 months; HR, 0.91; 95% CI, 0.61-1.36; P = 0.50), but not in hyperselection MUT tumors. Hyperselection status interacted with maintenance treatment arms in terms of PFS (P = 0.06) and OS (P = 0.009). CONCLUSIONS: Extended molecular profiling beyond RAS may have the potential to improve the patient selection for anti-EGFR containing maintenance regimens.
Assuntos
Neoplasias do Colo , Neoplasias Colorretais , Neoplasias Retais , Humanos , Panitumumabe , Anticorpos Monoclonais , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , Resultado do Tratamento , Fluoruracila/uso terapêutico , Leucovorina , Mutação , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêuticoRESUMO
Colorectal cancer is a common disease, both in Chile and worldwide. The most widely used chemotherapy schemes are based on 5-fluorouracil (5FU) as the foundational drug (FOLFOX, CapeOX). Genetic polymorphisms have emerged as potential predictive biomarkers of response to chemotherapy, but conclusive evidence is lacking. This study aimed to investigate the role of genetic variants associated with 5FU-based chemotherapy on therapeutic response, considering their interaction with oncogene mutations (KRAS, NRAS, PI3KCA, AKT1, BRAF). In a retrospective cohort of 63 patients diagnosed with metastatic colorectal cancer, a multivariate analysis revealed that liver metastases, DPYD, ABCB1, and MTHFR polymorphisms are independent indicators of poor prognosis, irrespective of oncogene mutations. BRAF wild-type status and high-risk drug-metabolism polymorphisms correlated with a poor prognosis in this Chilean cohort. Additionally, findings from the genomics of drug sensitivity (GDSC) project demonstrated that cell lines with wild-type BRAF have higher IC50 values for 5-FU compared to BRAF-mutated cell lines. In conclusion, the genetic polymorphisms DPYDrs1801265, ABCB1rs1045642, and MTHFRrs180113 may serve as useful biomarkers for predicting a poor prognosis in patients undergoing 5-fluorouracil chemotherapy, regardless of oncogene mutations.