Locally advanced or metastatic urothelial cancer is an aggressive form of cancer with high recurrence rates and low survival. Nectin-4 is a cell adhesion molecule commonly expressed in several tumors, including high expression in urothelial cancer. Enfortumab vedotin is an antibody-drug conjugate composed of an anti-Nectin-4 humanized monoclonal antibody linked to the microtubule disrupting agent, monomethyl auristatin E. In this phase I study (NCT03070990), Japanese patients with locally advanced/metastatic urothelial cancer treated with prior chemotherapy, or ineligible for cisplatin, were randomized 1:1 to receive 1.0 mg/kg (Arm A) or 1.25 mg/kg (Arm B) enfortumab vedotin on Days 1, 8, and 15 of each 28-day cycle. Assessing the pharmacokinetic and safety/tolerability profiles of enfortumab vedotin were primary objectives; investigator-assessed antitumor activity (RECIST v1.1) was a secondary objective. Seventeen patients (n = 9, Arm A; n = 8, Arm B) received treatment. Pharmacokinetic data suggest a dose-dependent increase in enfortumab vedotin maximum concentration and area under the concentration-time curve at Day 7. Enfortumab vedotin was well tolerated across both doses. Dysgeusia and alopecia (n = 9 each) were the most common treatment-related adverse events. Regardless of attribution, grade ≥ 3 adverse events occurring in ≥2 patients were anemia and hypertension (n = 2 each). One patient achieved a confirmed complete response (Arm A) and five achieved confirmed partial responses (n = 3, Arm A; n = 2, Arm B). Objective response and disease control rates were 35.3% and 76.5%, respectively. In Japanese patients with locally advanced/metastatic urothelial cancer, enfortumab vedotin is well tolerated with preliminary antitumor activity and a pharmacokinetic profile consistent with prior reports.
We compared the implant quality of intraoperatively built custom-linked (IBCL) seeds with loose seeds in permanent prostate brachytherapy. Between June 2012 and January 2015, 64 consecutive prostate cancer patients underwent brachytherapy with IBCL seeds (n = 32) or loose seeds (n = 32). All the patients were treated with 144 Gy of brachytherapy alone. Brachytherapy was performed using a dynamic dose calculation technique. Computed tomography/magnetic resonance imaging fusion-based dosimetry was performed 1 month after brachytherapy. Post-implant dose–volume histogram (DVH) parameters, prostate sector dosimetry, operation time, seed migration, and toxicities were compared between the IBCL seed group and the loose seed group. A sector analysis tool was used to divide the prostate into six sectors (anterior and posterior sectors at the base, mid-gland, and apex). V100 (95.3% vs 89.7%; P = 0.014) and D90 (169.7 Gy vs 152.6 Gy; P = 0.013) in the anterior base sector were significantly higher in the IBCL seed group than in the loose seed group. The seed migration rate was significantly lower in the IBCL seed group than in the loose seed group (6% vs 66%; P < 0.001). Operation time per seed was significantly longer in the IBCL seed group than in the loose seed group (1.31 min vs 1.13 min; P = 0.003). Other post-implant DVH parameters and toxicities did not differ significantly between the two groups. Our study showed more dose coverage post-operatively in the anterior base prostate sector and less seed migration in IBCL seed implantation compared with loose seed implantation.
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