Efficacy, Safety, and Tolerability of ONO-4474, an Orally Available Pan-Tropomyosin Receptor Kinase Inhibitor, in Japanese Patients With Moderate to Severe Osteoarthritis of the Knee: A Randomized, Placebo-Controlled, Double-Blind, Parallel-Group Comparative Study.

We examined the efficacy, safety, and tolerability of ONO-4474 in Japanese patients with osteoarthritis (OA) of the knee. In this multicenter, placebo-controlled, randomized, double-blind, parallel-group comparative study, patients with moderate to severe OA who were refractory to nonsteroidal anti-inflammatory drugs were orally administered 100 mg of ONO-4474 twice daily for 28 days. The primary end point was knee pain during walking, assessed by visual analog scale over 24 hours (VAS24 ). Treatment-emergent adverse events (TEAEs) and adverse drug reactions were reported for safety. In total, 110 patients were randomized (1:1) to receive placebo or ONO-4474. The mean (standard deviation) change in VAS24 scores at week 4 was -26.9 (25.0) mm in the ONO-4474 group and -19.5 (19.6) mm in the placebo group. The difference (ONO-4474 group - placebo group) in posterior mean change in VAS24 at week 4 was -5.8 (posterior standard deviation, 4.4; 95% confidence interval, -14.3 to 2.8) mm. TEAEs were reported in 41.8% of patients in the ONO-4474 group and 18.2% of patients in the placebo group. The most common TEAEs in the ONO-4474 group related to the musculoskeletal system and the peripheral and central nervous systems were myalgia (7.3%), arthralgia (5.5%), dizziness (3.6%), and hypoesthesia (3.6%). Four patients from the ONO-4474 group and 1 patient from the placebo group discontinued treatment because of AEs; however, none were judged to be serious, and all patients recovered or were recovering after discontinuation. ONO-4474 is a novel tropomyosin receptor kinase inhibitor that has an analgesic effect in patients with OA.

[Long-term disease-free survival following multimodal treatment in a patient with curatively unresectable advanced gastric cancer with metachronous liver metastasis].

A case was a 57-year-old man. Despite a diagnosis of cStage IV gastric cancer (cN2, cH0, cM0, cT3 (SE), cP1), we preferentially performed a non-curative surgery to avoid stenosis or bleeding by tumor invasion. Since no evidence of peritoneal metastasis was found at surgery, distal gastrectomy with D2 lymph node dissection was performed, and lymph nodes anterior to the pancreatic head were sampled. The pathological diagnosis was pT3 (SE), pN2, sH0, pM1 (LYM), pStage IV. After the surgery, S-1 was administered. One year and 9 months later, a solitary metastasis was found in S6 of the liver, and the patient underwent radiofrequency ablation (RFA) followed by adjuvant S-1. Currently, 5 years and 10 months after the surgery, the patient is under follow-up, and remains alive with recurrence-free. We speculate that in the presence of N or M (LYM) factors for stage IV gastric cancer, surgery with lymphadenectomy, which does not prevent the completion of adjuvant chemotherapy, followed by multimodal treatments such as continued chemotherapy and RFA, led to the long-term survival.