doxifluridine / Generic mfg. - LARVOL DELTA

Purification-Free Bortezomib-Drug Conjugates Optimize Drug Economy and Cancer Therapeutic Synergy. (PubMed, ACS Appl Mater Interfaces) - "Herein, we report a click conjugation strategy based on boronic acid-cis diol complexation, realizing a fast (<30 min), quantitative, and purification-free conjugation of bortezomib (BTZ) and azacytidine (AZA) or capecitabine or doxifluridine. Furthermore, BTZ and AZA could be conjugated into a polyprodrug with controlled size and composition, and different organelle uptakes augment the synergy of BTZ-AZA conjugate by approximately 1000-fold versus free BTZ toward A549 adenocarcinoma cells (IC50: 0.55 nM versus 536.7 nM). This click strategy would expand the vision for developing smart combination drugs."

Journal • Oncology

Doxifluridine promotes host longevity through bacterial metabolism. (PubMed, PLoS Genet) - "Furthermore, doxifluridine increases production of bacterial metabolites, such as linoleic acid and agmatine, to prolong host lifespan. Together, our results identify doxifluridine as a potent lead compound for rescuing aging-associated AS defects and extending lifespan, and elucidate drug's functions through complex interplay among drug, bacteria and host."

Journal

Ten-Year Follow-Up Clinical Outcomes and the Role of Adjuvant Chemotherapy in HER2-Positive Patients with Microinvasive Breast Cancer. (PubMed, Cancer Res Treat) - "Adjuvant chemotherapy was administered to 17.5% (n=140), with doxifluridine in 96.4% of cases. One patient (0.1%) received trastuzumab...Adjuvant chemotherapy did not improve survival, potentially due to the use of an outdated, ineffective regimen. The role of modern adjuvant regimens, particularly those incorporating HER2-targeted therapy, warrants further exploration."

Clinical data • Journal • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Breast Cancer • Oncology • Solid Tumor • ER • HER-2

Doxifluridine effectively kills antibiotic-resistant Staphylococcus aureus in chronic obstructive pulmonary disease. (PubMed, Microbiol Spectr) - "Future clinical trials will be essential to confirm these findings and pave the way for its integration into clinical practice. This work not only provides candidate for tackling the management of bacterial infections in COPD but also exemplifies the potential of drug repurposing in combating antibiotic-resistant infections."

Journal • Chronic Obstructive Pulmonary Disease • Hematological Disorders • Immunology • Infectious Disease • Oncology • Pulmonary Disease • Respiratory Diseases

Medroxyprogesterone-doxifluridine therapy for hormone-positive recurrent breast cancer with liver metastasis (JBCS 2024) - "During goserelin (G) + tamoxifen (TAM) treatment, liver metastasis and multiple bone metastasis occurred 3 years after surgery. After PR (7 months) with letrozole (LZ), PD, PD with exemestane (ET), and CR with medroxyprogesterone + doxifluridine (MD)...After 4 courses of AC, anastrozole (AZ) was administered for 10 years, multiple bone metastasis occurred in the 11th year, PD with AZ, PD with TAM, multiple liver metastasis in the 12th year, and CR with MD...PD was achieved after 1 year and 9 months of AZ, 1 month of LZ + palbociclib (PK), 10 months of fulvestrant (FT) + PK, and 12 months of FT + abemaciclib...Bone metastasis occurred 4 years and 3 months after surgery while administering leuprorelin and TAM...[Results and Discussion] All long survivors with liver metastasis who responded to MD were strongly ER and PgR positive. MD may be effective even in cases of liver metastases that have become resistant to TAM, AI, FT, and CDK inhibitors, and should be considered as..."

Breast Cancer • Endocrine Cancer • Hepatology • HER2 Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • HER-2 • PGR

A case of recurrent breast cancer with left brachial plexus metastasis discovered 20 years after surgery (JBCS 2024) - "After surgery, she received FEC therapy, oral doxifluridine for 2 years, oral anastrozole for 5 years, and radiation therapy (50 Gy) to the left supraclavicular fossa and parasternal lymph node area. (Summary) Brachial plexus injury due to recurrent breast cancer is a condition that can lead to irreversible paralysis if diagnosis and treatment are delayed. However, in cases where no mass is found around the brachial plexus, as in our case, it is difficult to diagnose, and it took time from the onset of symptoms to a definitive diagnosis"

Clinical • Surgery • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Musculoskeletal Pain • Oncology • Pain • Solid Tumor • HER-2

Study of triple-negative breast cancer at our hospital (JBCS 2024) - "However, at our hospital, chemotherapy is administered to 63% of TNBC patients, and 88.2% of these patients are treated with 5-DFUR/CPA, so the 5-year survival rate is relatively good and comparable. Conclusion Triple-negative breast cancer tends to be more elderly, and there are many cases in which intravenous chemotherapy is difficult to use, but administration of 5-DFUR/CPA can be used relatively safely even in elderly patients, and it has been suggested that it could be one of the effective treatments for reducing the recurrence rate"

Clinical • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Oral Cancer • Solid Tumor • Triple Negative Breast Cancer • HER-2

A case of breast cancer metastasis to endometrial polyps and uterine fibroids discovered approximately 10 years after surgery due to abnormal genital bleeding (JBCS 2024) - "After surgery, radiation therapy (60Gy) was performed on the conserved breast, chemotherapy (docetaxel, cyclophosphamide, furtulon), and hormone therapy (Zoladex + TAM)...After surgery, EC therapy was administered and exemestane was continued orally...There have been few reported cases of breast cancer metastasis to the uterus, and the prognosis is unknown, so it is thought that further accumulation of cases is necessary. This case is reported with a brief literature review"

Clinical • Surgery • Breast Cancer • Gynecology • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor • Uterine Cancer • Uterine Leiomyoma • Women's Health • HER-2

Three cases of breast angiosarcoma with different backgrounds (JBCS 2024) - "Doxifluridine and tamoxifen were administered as adjuvant therapy, but 2 years and 3 months after surgery, a rapidly growing tumor measuring 4 cm in diameter with skin infiltration and bleeding was found in the left conserved breast. There have been occasional reports of paclitaxel-containing regimens being effective in cases of recurrence, but in order to expect a good prognosis, the current situation is that there is no other option than to remove the tumor with a sufficient margin before it invades a wide area. In particular, tumors that grow rapidly have a poor prognosis, and in order to detect AS after Bp early, it is important not only to regularly screen the conserved breast, but also to educate patients so that they can respond quickly to changes in the breast"

Clinical • Anesthesia • Angiosarcoma • Breast Cancer • Hematological Disorders • Oncology • Rare Diseases • Respiratory Diseases • Sarcoma • Solid Tumor • Subarachnoid Hemorrhage

A case of coexistence of malignant phyllodes tumor and invasive ductal carcinoma that was difficult to diagnose (JBCS 2024) - "As it was considered that ② was also likely to be malignant, neoadjuvant chemotherapy (NAC): gemcitabine, vinorelbine, doxifluridine, cyclophosphamide-po, tamoxifen (TAM) was administered for both diagnosis and treatment. In addition, it is easy to overlook other diseases that exist at the same time, and it is difficult to select the surgical procedure, including the setting of the resection boundary, when performing surgical resection. Here, we report a very rare case of simultaneous ipsilateral giant malignant PT and IDC"

Clinical • Breast Cancer • Hematological Disorders • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Pain • Solid Tumor • HER-2

A Case of CDK4/6i-Resistant HR+/HER2- Multiple Liver and Bone Metastases Successfully Treated with Doxifluridine and Cyclophosphamide Combination Therapy (JBCS 2024) - "Method An 81-year-old woman had diffuse recurrence in the breast skin after partial resection of primary advanced axillary accessory breast cancer, and Palbociclib + Letrozole was effective, but 1 year and 7 months later, multiple liver and bone metastases, including metastases the size of a fist, occurred. The patient passed away 4 months later due to aspiration pneumonia and renal failure. Conclusion Doxifluridine + Cyclophosphamide combination therapy may be an option for metastatic or recurrent breast cancer that is refractory to CDK4/6 inhibitors"

Clinical • Combination therapy • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Infectious Disease • Oncology • Pneumonia • Renal Disease • Respiratory Diseases • Solid Tumor • CDK4 • HER-2

Two cases of postoperative lung metastasis of breast cancer treated with lung resection (JBCS 2024) - "After surgery, the patient was treated with ANA + furtulon (1 year), TAM + furtulon (5 years), and then continued with oral TAM...Pulmonary resection may reduce the amount of treatment required, and confirming the biology and providing appropriate postoperative therapy may contribute to extending the patient's survival. When there is uncertainty about the differential diagnosis of pulmonary nodules, it is considered important to maintain close cooperation on a daily basis so that consultations regarding surgical resection can be made with the thoracic surgery department"

Clinical • Breast Cancer • Gastric Cancer • Gastrointestinal Disorder • HER2 Breast Cancer • HER2 Positive Breast Cancer • Lung Cancer • Oncology • Solid Tumor • HER-2 • NKX2-1

A novel splicing factor, SPF45/RBM17, might influence 5-FU resistance of gastric carcinoma (AACR 2024) - "75 SPF45-positive-patients who received 5FU-based adjuvant chemotherapy (S-1, UFT, 5-DFUR) after surgery had significantly worse recurrence-free survival (RFS) than 140 SPF45-negative-patients (p=0.027)... Our results suggest that the splicing factor SPF45 influences anticancer drugs such as 5-FU resistance in gastric cancer.Acknowledgments: We thank Kazuhiro Fukumura and Akila Mayeda, Fujita Health University."

Gastric Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor • RBM17

Optimizing ex vivo culture conditions to study human gut microbiome. (PubMed, ISME Commun) - "Finally, we assessed the inter-individual metabolism by host gut microbiome from 10 donors on three frequently used clinical drugs (aspirin, levodopa and doxifluridine) based on the optimized GB medium. Our results revealed obvious variation in drug metabolism by microbiome from different donors, especially levodopa and doxifluridine. This work suggested the optimized culture medium had the potential for exploring the inter-individual impacts of host gut microbiome on drug metabolism."

Journal • Preclinical

Comparison of doxifluridine and tegafur/gimeracil/oteracil (S-1) as adjuvant chemotherapy for patients with gastric cancer after gastrectomy: A propensity score-matched analysis. (PubMed, Asian J Surg) - "There was no significant difference in the oncologic effect and patient compliance between DF and S-1 groups. DF could be an alternative option for adjuvant chemotherapy in advanced gastric cancer. In addition, we confirmed that relative dose intensity is an important independent prognostic factor for survival."

Journal • Gastric Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor

Diurnal Changes in Capecitabine Clock-Controlled Metabolism Enzymes Are Responsible for Its Pharmacokinetics in Male Mice. (PubMed, J Biol Rhythms) - "We then determined pharmacokinetics of capecitabine and its metabolites, 5'-deoxy-5-fluorocytidine (5'DFCR), 5'-deoxy-5-fluorouridine (5'DFUR), 5-fluorouracil (5-FU), in plasma and liver. Results indicated the levels of carboxylesterase 1 and 2, cytidine deaminase, uridine phosphorylase 2, and dihydropyrimidine dehydrogenase (p < 0.05) are being rhythmically regulated and, in turn, attributed different pharmacokinetics profiles of capecitabine and its metabolism. This study highlights the importance of capecitabine administration time to increase the efficacy with minimum adverse effects."

Journal • PK/PD data • Preclinical • Immunology • Oncology • CES1

Capecitabine induces hand-foot syndrome through elevated thymidine phosphorylase-mediated locoregional toxicity and GSDME-driven pyroptosis that can be relieved by tipiracil. (PubMed, Br J Cancer) - "Our findings reveal that the presence of elevated TP expression in the palm and sole aggravates local cell cytotoxicity, further explaining the molecular basis underlying 5-DFUR-induced cellular toxicity and providing a promising approach to the therapeutic management of HFS."

Journal • Dermatology • GSDME

Association between Timing and Duration of Adjuvant Chemotherapy and Colorectal Cancer Survival in Korea, 2011-2014: A Nationwide Study based on the Health Insurance Review and Assessment Service Database. (PubMed, J Cancer) - "Chemotherapy regimens were administered as follows: 10,640 (23.3%) received 5-fluorouracil and leucovorin/capecitabine (FL/CAP), 13,083 (28.7%) received FL/CAP plus oxaliplatin (FOLFOX/CAPOX), 299 (0.7%) received uracil and tegafur/doxifluridine (UFT/D), and 21,570 (47.3%) underwent surgery alone. Postoperative time to initiation and duration of AC were associated with survival. Based on our results, initiating AC within 2 months after surgery and administering AC for >3 months can potentially have an OS benefit in patients with stage II-III CRC."

Journal • Reimbursement • Review • Colon Cancer • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor

Construction of synergistic pH/HO-responsive prodrug for prolonging blood circulation and accelerating cellular internalization. (PubMed, Bioorg Chem) - "We have developed a real-time and multifunctional doxifluridine-conjugate prodrug (LYX), which involved the preliminary methylfluorescein with 5-fluorouracil linker as protecting group, the targeting biotin unit, and a model therapeutic drug (doxifluridine). The shielding group (5'-DFUR) was found to be effective in prolonging circulation at physiological pH 7.4 and improving accumulation in the acidic microenvironment of the tumor. Based on this strategy, the stability and stimulus responsive properties of prodrug could enhance drug release efficiency and exhibit fewer side effects, thereby providing a unique opportunity for diagnosis and imaging additional analytes or enzymatic activities."

Journal • Oncology

Fluoropyridmidine use and hypertriglyceridemia among Japanese patients: analysis of adverse event database. (PubMed, Int J Clin Pharm) - "Multivariate logistic analysis showed that both hypertriglyceridemia and an increase in serum triglyceride levels among fluoropyrimidines users were significantly associated with doxifluridine use (odds ratio [OR] 42.50; 95% CI 5.34-338.00; P < .001), tegafur use (OR 9.56; 95% CI 2.08-43.90; P < .001), capecitabine use (OR 12.30; 95% CI 2.67-56.80; P < .001), and breast cancer (OR 5.61; 95% CI 1.07-29.50; P = .042). Conclusion This study suggests that the use of tegafur and doxifluridine is associated with an increased risk of hypertriglyceridemia similar to that with the use of capecitabine; in particular, fluoropyrimidine users with breast cancer may have a high risk of hypertriglyceridemia."

Adverse events • Clinical • Journal • Breast Cancer • Dyslipidemia • Hypertriglyceridemia • Oncology • Solid Tumor

Comprehensive Study of the Risk Factors for Medication-Related Osteonecrosis of the Jaw Based on the Japanese Adverse Drug Event Report Database. (PubMed, Pharmaceuticals (Basel)) - "Factors that were significantly associated with MRONJ included eight types of BPs and denosumab, prednisolone, sunitinib, eldecalcitol, raloxifene, letrozole, doxifluridine, exemestane, radium chloride, medroxyprogesterone, female, elderly, and short stature. Furthermore, antiresorptive agents (i.e., BPs and denosumab) tended to induce MRONJ and atypical femoral fractures by affecting osteoclasts. We believe these findings will help medical personnel manage the side effects of many medications."

Adverse events • Clinical • Journal • Musculoskeletal Diseases • Orthopedics

Molecular Targeting of RRM2, NF-κB, and Mutant TP53 for the Treatment of Triple-Negative Breast Cancer. (PubMed, Mol Cancer Ther) - "Additionally, the use of Didox was also found to ameliorate the toxic myocardial effects of doxorubicin in vivo as measured by heart mass, left ventricular diameter, and serum troponin T levels. The data present a novel and promising approach for the treatment of TNBC that merits further clinical evaluation in humans."

Journal • Breast Cancer • Cardiovascular • Congestive Heart Failure • Estrogen Receptor Positive Breast Cancer • Heart Failure • Hormone Receptor Breast Cancer • Hormone Receptor Negative Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • ER • RRM2 • TP53

Doxifluridine-based pharmacosomes delivering miR-122 as tumor microenvironments-activated nanoplatforms for synergistic treatment of hepatocellular carcinoma. (PubMed, Colloids Surf B Biointerfaces) - "The integrated nanosystem (p122-ap1@NPC-D) was found to unleash by programmed TMEs (high level of HO and low pH) to efficiently transfect miR-122 into MHCC-LM3 cells, followed by the releases of 5-FU. Besides, p122-ap1@NPC-D significantly countered the chemotherapy resistance and played a synergistic effect. These unique nanoparticles dramatically enhanced the anti-proliferation, and modulated the cellular apoptosis by the down-regulation of various signal pathways which imparted a bright application prospect in HCC treatment."

Biomarker • Journal • Tumor microenvironment • Gastrointestinal Cancer • Hepatocellular Cancer • Hepatology • Oncology • Solid Tumor • EPCAM

Radiation-Associated Angiosarcoma That Developed in the Irradiated Residual Breast after Breast-Conserving Surgery for Breast Cancer-A Case Report and Review of the Literature (PubMed, Gan To Kagaku Ryoho) - "A7 2-year-old woman had undergone BCS for invasive ductal carcinoma of the right breast(pT2pN1M0, StageⅡB), followed by RT of 50 Gy; she was treated with doxifluridine and anastrozole for 5 year. RAAS is rare, but it should be considered in patients with skin lesions, such as erosion and bloody bulla, after BCS and RT for breast cancer. To our knowledge, only 12 cases of RAAS, including the present case, have been reported in Japan, and we reviewed the Japanese RAAS cases in comparison with those reported in the Western literature."

Clinical • Journal • Breast Cancer • Gastrointestinal Cancer • Hepatocellular Cancer • Liver Cancer • Oncology • Sarcoma • Solid Tumor

In Vitro Assessment of Fluoropyrimidine-Metabolizing Enzymes: Dihydropyrimidine Dehydrogenase, Dihydropyrimidinase, and β-Ureidopropionase. (PubMed, J Clin Med) - "Fluoropyrimidine drugs (FPs), including 5-fluorouracil, tegafur, capecitabine, and doxifluridine, are among the most widely used anticancer agents in the treatment of solid tumors. This is due to several studies that evaluated FP activities after enzyme metabolism using transient expression systems in Escherichia coli or mammalian cells; however, there are no comparative reports of these results. Thus, in this review, we summarized the results of in vitro analyses involving DPD, DHP, and β-UP in an attempt to encourage further comparative studies using these drug types and to aid in the elucidation of their underlying mechanisms."

Journal • Preclinical • Review • Oncology • Solid Tumor