To report long‐term results of a randomized controlled trial that compared cisplatin/fluorouracil/docetaxel (TPF) induction chemotherapy (IC) plus concurrent chemoradiotherapy (CCRT) with CCRT alone in locoregionally advanced nasopharyngeal carcinoma (NPC). Patients with stage III–IVB (except T3–4 N0) NPC were randomly assigned to receive IC plus CCRT (n = 241) or CCRT alone (n = 239). IC included three cycles of docetaxel (60 mg/m2 d1), cisplatin (60 mg/m2 d1), and fluorouracil (600 mg/m2/d civ d1–5) every 3 weeks. Patients from both groups received intensity‐modulated radiotherapy concurrently with three cycles of 100 mg/m2 cisplatin every 3 weeks. After a median follow‐up of 71.5 months, the IC plus CCRT group showed significantly better 5‐year failure‐free survival (FFS, 77.4% vs. 66.4%, p = 0.019), overall survival (OS, 85.6% vs. 77.7%, p = 0.042), distant failure‐free survival (88% vs. 79.8%, p = 0.030), and locoregional failure‐free survival (90.7% vs. 83.8%, p = 0.044) compared to the CCRT alone group. Post hoc subgroup analyses revealed that beneficial effects on FFS were primarily observed in patients with N1, stage IVA, pretreatment lactate dehydrogenase ≥170 U/l, or pretreatment plasma Epstein–Barr virus DNA ≥6000 copies/mL. Two nomograms were further developed to predict the potential FFS and OS benefit of TPF IC. The incidence of grade 3 or 4 late toxicities was 8.8% (21/239) in the IC plus CCRT group and 9.2% (22/238) in the CCRT alone group. Long‐term follow‐up confirmed that TPF IC plus CCRT significantly improved survival in locoregionally advanced NPC with no marked increase in late toxicities and could be an option of treatment for these patients.
Almost all patients with advanced prostate cancer (PCa) will eventually progress to incurable castration-resistant PCa (CRPC) if endocrine therapy fails. Therefore, identifying potential cellular targets is critical for the development of novel and effective treatments for CRPC. Based on the investigation of the molecular mechanism of ATN-224, an anticancer drug in clinical trials, in CRPC DU145 cells, the antioxidant enzyme catalase (CAT) has been recognized as an actionable CRPC therapeutic target, and the modulation of intracellular redox state through CAT inhibition has great potential for CRPC treatment. After systematic design and synthesis, the benzaldehyde thiosemicarbazone derivative BT-1 is shown to be effective CAT inhibitor in DU145 cells. This inhibition induces the significant increase of both superoxides (O 2 •−) and H 2 O 2 levels in DU145 cells. Finally, the dual pro-oxidant effect of BT-1 is demonstrated to lead to apoptosis as well as cell-cycle arrest in DU145 cells, effectively reducing CRPC tumors.
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