Fluorouracil

Incidence of squamous cell anal carcinoma (SCAC) is rising; ASCO's 2024 guideline recommends concurrent chemoradiation with mitomycin-C and 5-fluorouracil or capecitabine. Retifanlimab, a checkpoint inhibitor, showed improved progression-free survival and overall survival in phase 3 trials, potentially becoming a new standard of care for SCAC. SCAC, primarily HPV-driven, remains a significant unmet medical need with no FDA-approved treatments for advanced disease.

New research suggests 5-fluorouracil (5-FU) may primarily target ribosomal RNA, not DNA, in cancer cells, potentially changing future drug use. The study found 5-FU's efficacy depends more on RNA interaction than DNA damage, challenging long-held beliefs about its mechanism.

The FDA-AACR workshop on January 16, 2025, will explore DPD deficiency testing for 5-FU and capecitabine, addressing its benefits, harms, and current testing challenges. The workshop aims to educate and inform clinical decision-making, involving experts from various fields to discuss future directions and improve patient safety.

RAIDER trial compares standard whole-bladder treatment with adaptive approaches in bladder cancer, showing safe dose escalation and maintained quality of life. 345 patients across 46 centers benefit from multiple treatment plans, with encouraging outcomes in the dose-escalated adaptive arm. Challenges include quality assurance for radiotherapy technicians and questions about whole-pelvis vs. bladder-only treatment and concurrent chemotherapy.

CM24 plus nivolumab and SOC chemotherapy improved OS (7.92 vs 5.55 months), PFS (3.9 vs 2.0 months), ORR (25% vs 7%), and DCR (63% vs 47%) in metastatic PDAC patients compared to SOC chemotherapy alone. CM24, a multi-functional antibody blocking CEACAM1, showed enhanced efficacy in biomarker-enriched populations, prompting further investigation in a phase 2b study targeting multiple indications.

Risperidone, a second-generation antipsychotic, treats schizophrenia, bipolar disorder, and autism-related hyperactivity. It inhibits D2 dopamine and 5-HT2A serotonin receptors, reducing psychotic symptoms. Risperidone nano/microcarriers enhance bioavailability, reduce side effects, and improve patient compliance. Formulation strategies include liposomes, nanoparticles, nanoemulsions, and niosomes, aiming to improve solubility, stability, and targeted delivery. Toxicological studies highlight neurological and immunosuppressive side effects. Clinical trials show efficacy in psychosis management, and patents focus on innovative formulations. Future research aims to optimize nano/microcarrier systems for better drug delivery.

The ARMANI trial shows that switching to maintenance ramucirumab–paclitaxel after 3 months of induction chemotherapy improves outcomes for patients with unresectable HER2-negative G/GEJC.

DEEPER was a multicenter, randomized, open-label, phase 2 trial comparing m-FOLFOXIRI + cetuximab and m-FOLFOXIRI + bevacizumab in unresectable RAS wild-type mCRC. Patients were randomly assigned 1:1, stratified by primary tumor site, adjuvant chemotherapy history, and ECOG PS. Treatments were administered up to 12 cycles, with cetuximab or bevacizumab, followed by maintenance therapy. The primary endpoint was depth of response (DpR), with secondary endpoints including ORR, ETS, PFS, OS, TTG, R0 resection rate, and safety. Statistical analysis included t-test, chi-squared test, and log-rank test, with post-hoc exploratory analysis by BRAF status.

A phase II trial investigated triplet antiemetic therapy (PALO, APR, OLN) for breast cancer patients undergoing HEC. Conducted from 2019-2022, it involved 8 institutions, enrolling patients aged 20+ with ECOG PS 0–2. Treatment included PALO 0.75 mg, OLN 5 mg for 5 days, and APR 125 mg or fosaprepitant 150 mg. Primary endpoint was TC rate of nausea/vomiting (0–120 h), with secondary endpoints including TC rates in acute/delayed phases, CR of vomiting, CC of nausea/vomiting, and severity of nausea. Statistical analysis aimed to verify TC rate >23% with 80% power, requiring 74 cases, adjusted to 89 considering dropout rate.