Fluorouracil
- Generic Name
- Fluorouracil
- Brand Names
- Actikerall, Carac, Efudex, Fluoroplex, Tolak
- Drug Type
- Small Molecule
- Chemical Formula
- C4H3FN2O2
- CAS Number
- 51-21-8
- Unique Ingredient Identifier
- U3P01618RT
- Background
A pyrimidine analog that is an antineoplastic antimetabolite. It interferes with DNA synthesis by blocking the thymidylate synthetase conversion of deoxyuridylic acid to thymidylic acid.
- Indication
For the topical treatment of multiple actinic or solar keratoses. In the 5% strength it is also useful in the treatment of superficial basal cell carcinomas when conventional methods are impractical, such as with multiple lesions or difficult treatment sites. Fluorouracil injection is indicated in the palliative management of some types of cancer, including colon, esophageal, gastric, rectum, breast, biliary tract, stomach, head and neck, cervical, pancreas, renal cell, and carcinoid.
- Associated Conditions
- Actinic Keratosis (AK), Breast Cancer, Colon Cancer, Gastric Cancer, Pancreatic Cancer, Rectal Cancer, Superficial Basal Cell Carcinoma, Verruca (Warts), Hyperkeratotic actinic keratosis
Merck and Daiichi Sankyo Launch Phase 3 Trial of Novel B7-H3 Targeted ADC for Advanced Esophageal Cancer
• The IDeate-Esophageal01 Phase 3 trial has begun evaluating ifinatamab deruxtecan, a potential first-in-class B7-H3 directed antibody-drug conjugate, against standard chemotherapy in advanced esophageal squamous cell carcinoma.
• Esophageal squamous cell carcinoma accounts for 90% of global esophageal cancers with dismal survival rates of 15-20%, highlighting the urgent need for new treatment approaches after first-line therapy failure.
• The trial follows promising early-phase results and will enroll approximately 510 patients across Asia, Europe, and North America, with overall survival as the primary endpoint.
TFOX Regimen Shows Superior Efficacy Over FOLFOX in Advanced HER2-Negative Gastric Cancer
• French phase III PRODIGE 51-FFCD-GASTFOX trial demonstrates modified FLOT regimen (TFOX) significantly improves progression-free and overall survival compared to FOLFOX in advanced HER2-negative gastric cancer.
• The TFOX regimen achieved a median overall survival of 15.1 months versus 12.7 months with FOLFOX, along with higher objective response rates (62.3% vs 53.4%) despite increased toxicity.
• Researchers suggest TFOX represents a promising new first-line treatment option for patients eligible for docetaxel triplet chemotherapy, particularly those under 70 with good performance status.
JNJ-1900 Shows Promise in Phase 1 Trial for Advanced Pancreatic Cancer
• JNJ-1900 (NBTXR3) demonstrated favorable safety and feasibility in a Phase 1 trial involving 22 patients with locally advanced or borderline resectable pancreatic cancer.
• The trial showed encouraging efficacy with a median overall survival of 23 months from diagnosis, compared to 19.2 months with standard care in a historical review.
• Exploratory biomarker analyses revealed CA19-9 normalization in 59% of patients, associated with improved survival, and increased circulating tumor mutational burden in 40% of patients.
NCCN Updates Guidelines to Recommend DPYD Testing Before Fluoropyrimidine Chemotherapy
• The National Comprehensive Cancer Network (NCCN) has updated its clinical guidelines to recommend considering DPYD genotyping before initiating fluoropyrimidine-based chemotherapy for cancer patients.
• Approximately 6% of individuals carry pathogenic DPYD variants, which can cause severe or fatal toxicity to common chemotherapy drugs like 5-fluorouracil (5-FU) and capecitabine used in treating colon, rectal, and gastrointestinal cancers.
• Clinical data shows that genotype-guided dosing significantly reduces severe toxicity from 73% to 28% in DPYD variant carriers while maintaining treatment effectiveness, representing a major advancement in personalized cancer care.
Robust Pipeline of 200+ Therapies Targets Colorectal Cancer Treatment Landscape
• DelveInsight's latest report reveals a robust pipeline with over 195 companies developing 200+ therapies for colorectal cancer, highlighting significant innovation in targeted treatments and immunotherapies.
• Key drug candidates include XL092 (Exelixis), Adagrasib (Mirati Therapeutics), Olaparib (Merck/AstraZeneca), and novel approaches like LYL845, an autologous tumor-infiltrating lymphocyte therapy from Lyell Immunopharma.
• The metastatic colorectal cancer segment shows particular promise with 150+ companies advancing 180+ pipeline therapies, including innovative treatments targeting specific mutations and immune pathways.
Immunotherapy in Gastric Cancer: Moving to Earlier Disease Stages and Optimizing Combination Approaches
• Leading oncologist Dr. Yelena Janjigian emphasizes the need to advance immunotherapy to earlier disease stages in gastric, GEJ, and esophageal cancers, with promising data expected from the MATTERHORN study.
• Recent evidence from phase 3 trials TOPGEAR and ESOPEC demonstrates that radiation therapy does not improve survival outcomes in gastric/GEJ cancers, challenging conventional treatment approaches.
• FLOT chemotherapy regimen combined with durvalumab represents an optimal treatment strategy for the perioperative setting, addressing the systemic nature of gastric cancer rather than focusing on localized radiation therapy.
Isofol Medical Advances Arfolitixorin Development with New Phase Ib/II Trial for Metastatic Colorectal Cancer
• Isofol Medical has received regulatory approval to initiate a Phase Ib/II clinical trial evaluating arfolitixorin in first-line treatment of metastatic colorectal cancer at Germany's prestigious Charité Universitätsmedizin Berlin.
• The new study implements an optimized dosing regimen with higher doses administered earlier in the treatment cycle, designed to enhance arfolitixorin's synergistic effects with 5-FU chemotherapy.
• The trial will replace leucovorin with arfolitixorin in standard treatment protocols and will be conducted in two stages: dose escalation assessment followed by efficacy comparison between selected dosages.
OSE2101 Cancer Vaccine Shows Promising Results in Phase 2 Pancreatic Cancer Trial
• The TEDOPaM Phase 2 trial met its primary endpoint, demonstrating that OSE2101 (Tedopi) combined with FOLFIRI chemotherapy achieved a statistically significant improvement in one-year overall survival rate for advanced pancreatic cancer patients.
• The neoepitope-based therapeutic cancer vaccine showed minimal toxicity when used as maintenance therapy in HLA-A2 positive patients who had not progressed after FOLFIRINOX induction chemotherapy.
• Researchers emphasize these results provide hope in a difficult-to-treat cancer with low survival rates, though further analysis and longer follow-up are needed to fully understand the vaccine's contribution to the observed benefits.
Enhertu Demonstrates Significant Overall Survival Benefit in HER2-Positive Breast Cancer Phase III Trial
• Daiichi Sankyo and AstraZeneca's Enhertu (trastuzumab deruxtecan) achieved significant overall survival improvement in HER2-positive breast cancer patients during Phase III clinical trial.
• The antibody-drug conjugate showed promising efficacy results, reinforcing its potential as a breakthrough therapy for advanced breast cancer patients who have limited treatment options.
• The successful trial outcomes further strengthen Enhertu's position in the breast cancer treatment landscape, building upon its previous FDA approvals.
Atezolizumab Shows Promise Following Chemoradiotherapy in Advanced Esophageal Cancer
• A phase II trial demonstrated that atezolizumab immunotherapy following definitive chemoradiotherapy achieved a 42.1% complete response rate in patients with unresectable locally advanced esophageal squamous cell carcinoma.
• The combination treatment showed manageable safety with a 65.8% one-year overall survival rate, suggesting potential long-term survival benefits without additional safety concerns.
• Molecular analyses revealed that chemoradiotherapy enhanced antitumor immune responses through multiple pathways, providing strong rationale for sequential combination with PD-L1 blockade.
Auckland Researchers Launch Clinical Trial to Investigate 5FU Chemotherapy Cardiotoxicity
• University of Auckland and Auckland City Hospital researchers initiate a clinical trial to study severe cardiac side effects of 5-fluorouracil (5FU), a widely-used chemotherapy drug affecting 5% of patients.
• The two-year study, funded by multiple organizations including the Gut Cancer Foundation, aims to identify risk factors and mechanisms behind 5FU-induced cardiotoxicity through comprehensive patient monitoring.
• Researchers will utilize Holter monitors, blood tests, and urine samples from cancer patients to understand drug metabolism patterns and develop predictive markers for adverse cardiac reactions.
Triple Combination of Envafolimab, Suvemcitug, and FOLFIRI Shows Promise in Advanced Colorectal Cancer
• Phase 2 trial demonstrates 25% objective response rate and 90% disease control rate in patients with microsatellite stable colorectal cancer treated with envafolimab-suvemcitug-FOLFIRI combination.
• The treatment showed manageable safety profile with no treatment discontinuations due to adverse effects, though 90% of patients experienced grade 3 or higher treatment-related events.
• Median progression-free survival reached 5.6 months, with particularly encouraging response rates of 36.4% observed in patients with lung metastases.
Study Reveals Major Disparities in US Health Plan Coverage of Pharmacogenetic Testing
• A comprehensive analysis of major US health insurers found significant variability in coverage policies for pharmacogenetic tests, with most plans covering 10 or fewer of 65 clinically relevant drug-gene pairs.
• Medicare's Molecular Diagnostic Services program provided the broadest coverage, including all 65 drug-gene pairs, while only three insurers covered multi-gene panel testing despite evidence of clinical benefits.
• Society guidelines were the most frequently cited evidence for coverage decisions, while cost-effectiveness studies were rarely considered, highlighting the need for standardized evidence evaluation processes.
Novel Topical Drug Delivery Systems Show Promise in Revolutionizing Breast Cancer Treatment
• Breast cancer claimed over 650,000 lives globally in 2022, driving urgent research into more effective and less toxic treatment approaches.
• Innovative topical delivery systems, including transfersomal formulations and iontophoresis, demonstrate enhanced drug penetration and reduced systemic side effects compared to traditional oral medications.
• Studies reveal the nipple-areola complex's unique anatomy offers advantages for targeted drug delivery, with trials showing higher breast tissue concentrations through topical application versus intravenous routes.
NALIRIFOX Shows Numerically Improved Overall Survival Compared to FOLFIRINOX in Metastatic PDAC
• A real-world study indicated that first-line NALIRIFOX had a numerically higher median overall survival (OS) of 11.1 months compared to FOLFIRINOX's 9.1 months in mPDAC patients.
• The analysis included a trial-aligned cohort, an all-comer cohort, and a modified FOLFIRINOX cohort, assessing survival outcomes in metastatic pancreatic ductal adenocarcinoma.
• The findings suggest NALIRIFOX may offer a survival advantage over FOLFIRINOX in treating mPDAC, warranting further studies adjusting for baseline characteristics.
• Data were sourced from the Flatiron Electronic Health Record, covering patients treated between January 2014 and February 2024, providing a comprehensive real-world view.
Gastrointestinal Cancer Symposium 2025: Key Advances in Treatment Strategies
• Nivolumab plus ipilimumab demonstrates superior progression-free survival compared to nivolumab alone in MSI-H/dMMR metastatic colorectal cancer.
• Encorafenib combined with cetuximab and chemotherapy shows significant improvement in overall response rate for BRAF V600E-mutated metastatic colorectal cancer.
• TACE plus camrelizumab and rivoceranib extends progression-free survival in patients with unresectable hepatocellular carcinoma, offering a manageable safety profile.
FDA Approves Sotorasib Plus Panitumumab for KRAS G12C-Mutated Metastatic Colorectal Cancer
• The FDA has approved sotorasib (Lumakras) in combination with panitumumab (Vectibix) for treating KRAS G12C-mutated metastatic colorectal cancer in adults who have received prior chemotherapy.
• This approval is based on the Phase 3 CodeBreaK 300 trial, which demonstrated a significant improvement in progression-free survival compared to standard of care.
• The combination therapy led to a median progression-free survival of 5.6 months, a substantial increase compared to the 2 months observed with standard treatments.
• The FDA also approved the therascreen KRAS RGQ PCR Kit as a companion diagnostic to identify patients eligible for this targeted treatment approach.
Radiomics in Rectal Cancer: A Powerful Tool for Diagnosis, Treatment Response Evaluation, and Prognosis Prediction
• Radiomics, an advanced computational approach that extracts quantitative features from medical images, is revolutionizing rectal cancer management by providing more accurate tumor staging and treatment response prediction than conventional imaging methods.
• Recent studies demonstrate radiomics' effectiveness in predicting lymph node metastasis, distant metastasis, and pathological complete response to neoadjuvant therapy, with multimodal approaches combining CT, MRI, and ultrasound showing the highest predictive accuracy.
• The integration of radiomics with deep learning algorithms and molecular markers represents the future direction of research, potentially enabling more personalized treatment strategies and improved patient outcomes in rectal cancer care.
BioNTech Advances Oncology Pipeline with BNT327/PM8002 and mRNA Immunotherapies
• BioNTech is progressing BNT327/PM8002, a bispecific antibody, into global clinical trials for first-line small cell lung cancer and non-small cell lung cancer.
• The company plans to initiate additional trials combining BNT327/PM8002 with antibody-drug conjugates (ADCs) in 2025, expanding its combination strategy.
• BioNTech's mRNA cancer immunotherapy, autogene cevumeran, is being evaluated in a Phase 2 trial for muscle-invasive urothelial carcinoma in combination with nivolumab.
• Clinical data readouts are expected in 2025 and 2026 from multiple randomized trials of personalized and off-the-shelf mRNA cancer immunotherapy candidates.
Arvinas Advances Vepdegestrant into Phase 3 Trials for Breast Cancer and Updates Pipeline Milestones
• Arvinas plans to initiate two Phase 3 trials in 2025 for vepdegestrant in ER+/HER2- metastatic breast cancer, one in the first-line setting with atirmociclib and another in the second-line setting with a CDK4/6 inhibitor.
• Topline data from the Phase 3 VERITAC-2 monotherapy trial of vepdegestrant in second-line-plus ER+/HER2- metastatic breast cancer is anticipated in the first quarter of 2025.
• Arvinas is set to present initial data from the Phase 1 trial of ARV-393 in B-cell lymphomas and file an IND application for a novel PROTAC KRAS G12D degrader in 2025.
• Phase 1 trial with PROTAC LRRK2 degrader ARV-102 in patients with Parkinson’s disease has been initiated, with data expected to be presented in the first half of 2025.
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