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Purpose: This trial assessed the safety, pharmacokinetics, and efficacy of darolutamide (ODM-201), a new-generation nonsteroidal androgen receptor antagonist, in Japanese patients with metastatic castration-resistant prostate cancer (mCRPC).Methods: In this open-label, nonrandomized, two-cohort, dose-escalating phase 1 study, Japanese patients with mCRPC were enrolled after a screening period. In the single-dose period (≈1 week), darolutamide was administered at 300 mg (Cohort 1) or 600 mg (Cohort 2) on day -5 (fasting state) and day -2 (fed condition). In the subsequent multiple-dose period (fed condition), patients received darolutamide 300 mg twice daily (Cohort 1) or 600 mg twice daily (Cohort 2) for 12 weeks. Primary endpoints: evaluate safety and pharmacokinetics of darolutamide.Results: Of 12 patients enrolled, 9 received darolutamide (Cohort 1, n = 3; Cohort 2, n = 6). All 9 patients experienced ≥1 treatment-emergent adverse event (TEAE; majority Grade 1/2). Incidence of drug-related TEAEs (DR-TEAEs) was 44% (all grades; n = 4); most common DR-TEAE was decreased appetite (22%), and 1 serious DR-TEAE (Grade 3 nausea) was observed. No Grade ≥4 DR-TEAEs or new safety signals were observed. C max and AUC (0-t last) were dose-dependent; pharmacokinetics of each dose appeared to be linear over time. Prostate-specific antigen response was observed in 11% (1/9) of patients. Compared with fasting status, geometric mean C max increased 2.5-fold after 300 mg and 2.8-fold after 600 mg; geometric mean AUC (0-t last) increased 2.5-fold after both doses under fed conditions.Conclusions: Darolutamide was well tolerated at the examined doses in Japanese patients with mCRPC, without differences in safety and pharmacokinetics relative to Western patients. [ABSTRACT FROM AUTHOR]

Follicular dendritic cell sarcoma (FDCS) is a very rare malignant tumor derived from follicular dendritic cells. Radical resection is the standard therapy for patients with local disease, but an optimal chemotherapy regimen has not been determined for unresectable disease. We report our experience of an FDCS patient with multiorgan involvement. In the present case, disease was only located in the pancreas initially and radical resection was performed. Multiple metastasis developed after the treatment and several factors that indicated a poor prognosis were observed. The present case had a very poor prognostic disease but survived for a long time with a good performance status because of the multiple chemotherapy regimens, which follow therapeutic strategies for malignant lymphoma and soft tissue sarcoma. As far as we know, this is the first study reporting the indication of bendamustine for FDCS patients. [ABSTRACT FROM AUTHOR]

Background K-912 also known as NC-6300 is a novel epirubicin pro-drug conjugate developed using micellar nanoparticle technology. We conducted a first-in-human, Phase 1, open-label, non-randomized dose escalation study to evaluate the safety, tolerability, efficacy, and pharmacokinetics of K-912 administered as monotherapy in patients with advanced or recurrent solid tumors. Methods Patients aged 41 to 72 years with histologically or cytologically confirmed advanced or recurrent malignant solid tumors either refractory to standard therapy or had no other viable treatment options were enrolled. K-912 was administered as a 10-min intravenous infusion every three weeks. Doses were increased in a step-wise manner based on a predetermined series: 15, 30, 60, 80, 100, 130, 170, and 225 mg/m. The appropriateness of doses above 60 mg/m was assessed using a Bayesian continual reassessment model. Treatment-emergent adverse events and tumor response were evaluated according to internationally accepted criteria. Results Nineteen patients were treated with K-912. No additional adverse events expected with anthracyclines were observed. While the number of patients treated at the maximum tolerated dose (MTD) and the recommended phase 2 dose (RP2D) were small, MTD and RP2D were established to be 170 mg/m. Partial response was observed in one patient with breast cancer treated at 100 mg/m, yielding an objective response rate of 5% (1/19). Stable disease was observed in 10 patients. The human pharmacokinetic profile of K-912 was consistent with that observed from nonclinical studies in rats and monkeys. Conclusions This study showed that K-912 was well tolerated in patients with various solid tumors and exhibited less toxicity than conventional epirubicin formulations. [ABSTRACT FROM AUTHOR]

This phase I study in Japanese patients evaluated the safety, pharmacokinetics, and preliminary efficacy of palbociclib, a highly selective and reversible oral cyclin-dependent kinase 4/6 inhibitor, as monotherapy for solid tumors (part 1) and combined with letrozole as first-line treatment of postmenopausal patients with estrogen receptor-positive, human epidermal growth factor receptor 2-negative advanced breast cancer (part 2). Part 1 evaluated palbociclib 100 and 125 mg once daily (3 weeks on/1 week off; n = 6 each group) to determine the maximum tolerated dose. Part 2 evaluated palbociclib maximum tolerated dose (125 mg) plus letrozole 2.5 mg ( n = 6). The most common treatment-related adverse event was neutropenia (all grades/grade 3/4): 100 mg, 83%/67%; 125 mg, 67%/33%; and palbociclib plus letrozole, 100%/83%. Heavier pretreatment with chemotherapy may have resulted in higher neutropenia rates observed with the 100-mg dose. Palbociclib exposure was higher with 125 vs 100 mg (mean area under the plasma concentration-time curve over dosing interval [τ]: 1322 vs 547.5 ng·h/mL [single dose], 2838 vs 1276 ng·h/mL [multiple dose]; mean maximum plasma concentration: 104.1 vs 41.4 ng/mL [single dose], 185.5 vs 77.4 ng/mL [multiple dose]). Half-life was 23-26 h. No drug-drug interactions between palbociclib and letrozole occurred. Four patients had stable disease (≥24 weeks in one patient with rectal cancer [100 mg] and one with esophageal cancer [125 mg]) in part 1; two patients had partial response and two had stable disease (both ≥24 weeks) in part 2. Palbociclib at the 125-mg dose (schedule 3/1) was tolerated and is the recommended dose for monotherapy and letrozole combination therapy in Japanese patients. The trials are registered with : A5481010 and NCT01684215. [ABSTRACT FROM AUTHOR]

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The research question of this investigation is whether the reduction rate of Ki-67 after neoadjuvant chemotherapy (NAC) could indicate a survival in patients with non-pCR. A total of 455 patients had received NAC, and subsequent surgery was analyzed retrospectively. Patients with non-pCR were divided into three subgroups according to Ki-67 change: High-reduction (the absolute value of Ki-67 was reduced by >80 % compared with that prior to NAC), Low-reduction (the absolute value of Ki-67 was reduced by 0-80 % compared with that prior to NAC), and Increase group (the absolute value of Ki-67 was increased compared with that prior to NAC). The relapse-free survival (RFS) rates were compared among subgroups. pCR was achieved in 93 patients (20.4 %). In patients with non-pCR, the median reduction rate of Ki-67 was 60 %. A total of 15 % of patients were in the High-reduction, 63 % in the Low-reduction, and 22 % in the Increase group. The median follow-up period was 64.5 months. The 5-year RFS rates among the three groups were significantly different ( p < 0.0001), and the differences were also observed in the HER2 ( p = 0.033), triple-negative ( p = 0.034), and luminal-like subtypes ( p = 0.001). Patients in the High-reduction group showed comparable RFS to that of patients with pCR ( p = 0.363). In patients with non-pCR, the reduction rate of Ki-67 after NAC significantly predicted RFS regardless of cancer subtypes. Therefore, patients who are non-pCR but who achieve a high reduction of Ki-67 can be expected to have a favorable prognosis similar to that of patients with pCR. [ABSTRACT FROM AUTHOR]