Efficacy and safety of talazoparib in Japanese patients with germline BRCA-mutated locally advanced or metastatic breast cancer: results of the phase 1 dose-expansion study.

BACKGROUND: Talazoparib, a poly(ADP-ribose) polymerase enzyme inhibitor, is approved for the treatment of patients with germline BRCA1/2 (gBRCA1/2)-mutated HER2-negative advanced breast cancer. This two-part study, a recently published dose-escalation part followed by the dose-expansion part reported here, evaluated the efficacy and safety of talazoparib in Japanese patients with gBRCA1/2-mutated advanced breast cancer. METHODS: In this open-label, multicenter phase 1 study (NCT03343054), the primary endpoint of the dose-expansion part was confirmed objective response rate (ORR), determined by investigator assessment (RECIST 1.1). Secondary endpoints included progression-free survival (PFS), overall survival (OS), safety, and pharmacokinetics. Patients received the recommended phase 2 dose (1 mg/day; 0.75 mg/day moderate renal impairment). RESULTS: Nineteen Japanese patients with gBRCA1/2-mutated locally advanced or metastatic breast cancer were enrolled. Confirmed ORR was 57.9% (11/19; 90% confidence interval [CI] 36.8-77.0). Stable disease was observed in 36.8% (7/19) of patients. Per investigator assessment, median PFS was 7.2 months (95% CI 4.1-not estimable) and 12-month OS rate was 84.7% (90% CI 57.5-95.1). Median OS was not reached; 17/19 patients were alive and censored at 12 months. All patients experienced treatment-related adverse events (AEs); the majority were hematologic. The most common treatment-related AE was anemia (68.4%; [13/19]). Grade 3/4 treatment-related AEs were observed in 52.6% (10/19) of patients. During the safety period, there were no grade 5 treatment-emergent AEs, treatment-related serious AEs, or deaths. CONCLUSIONS: In Japanese patients with gBRCA mutations and locally advanced or metastatic breast cancer, talazoparib monotherapy was generally well tolerated and resulted in clinically meaningful ORRs. GOV IDENTIFIER: NCT03343054.

Association of Lifestyle Changes Due to the COVID-19 Pandemic with Nutrient Intake and Physical Activity Levels during Pregnancy in Japan.

The coronavirus disease 2019 (COVID-19) pandemic has introduced changes in our lifestyles, such as refraining from unnecessary outings. This study aimed to clarify the association of lifestyle changes due to the COVID-19 pandemic with nutrient intake and physical activity levels during pregnancy in Japan. A cross-sectional study involving 168 healthy pregnant Japanese women was conducted in 2020. Nutrient intake and physical activity levels were assessed using validated self-administered questionnaires. Participants who reported experiencing changes in both dietary habits and physical activity due to the COVID-19 pandemic were classified as the lifestyle-affected group. Analysis of covariance was used. Among primiparas, intake of the following nutrients was significantly higher in the lifestyle-affected group (n = 14) than in the unaffected group (n = 77): protein, potassium, calcium, magnesium, and vitamin B6. Among multiparas, the intake of dietary fiber and ß-carotene were significantly lower in the lifestyle-affected group (n = 13) than in the unaffected group (n = 64). No significant differences in physical activity levels were observed in accordance with the lifestyle changes. These findings suggest that lifestyle changes due to the COVID-19 pandemic have positive effects on nutrient intake during pregnancy in primiparas, whereas in multiparas, these changes have negative effects.

Safety, pharmacokinetics, and preliminary efficacy of the PARP inhibitor talazoparib in Japanese patients with advanced solid tumors: phase 1 study.

BACKGROUND: Talazoparib is a poly(ADP-ribose) polymerase enzyme inhibitor. This open-label, non-randomized, phase 1 study of talazoparib investigated the safety, pharmacokinetics, and preliminary antitumor activity in Japanese patients with locally advanced or metastatic solid tumors, regardless of mutations in DNA damage repair-related genes, who are resistant to/ineligible for standard therapies. METHODS: Patients received talazoparib dosed orally at 0.75 or 1 mg once daily using a modified 3 + 3 dose-escalation scheme. Primary endpoint was dose-limiting toxicities during the first cycle of talazoparib. RESULTS: Nine patients (median age 62.0 years) were included: 3 and 6 patients at the 0.75 and 1.0 mg once-daily dose levels, respectively. No dose-limiting toxicities were reported. The most commonly reported treatment-emergent adverse events (≥2 patients) were anemia, stomatitis, maculopapular rash, platelet count decreased, neutrophil count decreased, and alanine aminotransferase increased. Three patients had grade ≥ 3 treatment-emergent adverse events (anemia, brain metastases [1 patient each], and neutrophil and white blood cell count decreased [same patient]). Two patients temporarily discontinued treatment due to a treatment-emergent adverse event, and 1 patient required a dose reduction for neutrophil count decreased (all at 1 mg once daily). Talazoparib exposure (Cmax and AUC) after single and multiple dosing was slightly higher proportionally with talazoparib 1 mg than talazoparib 0.75 mg. The overall disease control rate was 44.4%, including 2 patients with stable disease. The recommended phase 2 dose of talazoparib was established as 1 mg once daily. CONCLUSIONS: Single-agent talazoparib was well tolerated and had preliminary antitumor activity in Japanese patients with advanced solid tumors. ClinicalTrials.gov identifier: NCT03343054 (November 17, 2017).

Assessment of reasons for referral and activities of hospital palliative care teams using a standard format: a multicenter 1000 case description.

CONTEXT: The many benefits of hospital palliative care teams (PCTs) are well known. However, their specific activities have not been fully clarified, and no standardized methods for reporting PCT activities are available. OBJECTIVES: The aim of this study was to investigate, through the use of a standard format, the activities performed by hospital PCTs in Japan. METHODS: This was a prospective observational study. A total of 21 hospital PCTs were included in this study, and each recruited approximately 50 consecutively referred patients. Participating PCTs filled in a standard form for reporting activities. RESULTS: We obtained data from 1055 patients who were referred to PCTs. Of the 1055 patients, 1005 patients (95%) had cancer. The median number of reasons for referral and problems identified by PCTs was two (0-22) and four (0-18), respectively. The two major reasons for referral were pain (63%) and anxiety/depression/grief/emotional burden (22%). The major recommendations were pharmacological treatment (74%), care for the patient's physical symptoms (49%), and support for patient's decision making (38%). The major activities performed by the PCTs were comprehensive assessment (90%), care for the patient's physical symptoms (77%), and pharmacological treatment (74%). CONCLUSION: The components of hospital PCT activities were successfully measured using the Standard Format for Reporting Hospital PCT Activity. The results of this study and the format for reporting hospital PCT activity could be effective in improving hospital PCT practice and for the education of new hospital PCT members.

[Urological oncology emergencies].

Urologic emergencies in malignancies are difficult to treat for non-urological medical staff because of their anatomical specificity and sensational susceptibility. Urological cancer pain involves somatic and neuropathic problems. In pelvic malignancies, almost always NSAIDs, micro-2-agonisitic opioids and adjuvant analgesics are necessary for pain palliation. The inducements of hemorrhagic cystitis are radiation, chemotherapy and tumor invasion. Although there are some conservative treatments such as hyperbaric oxygen therapy for radiation-induced hemorrhagic cystitis, in emergency circumstances selective embolization of the internal iliac artery may be beneficial with fewer side effects. In uncontrollable tumor bleeding, palliative radiotherapy(maximum dose of 30-36 Gy)is effective. The most important problem in voiding disturbance is bladder outlet obstruction. Sometimes patients are treated with alfa-adrenergic blockers effectively, but eventually they may need an indwelling catheter. Obstructive nephropathy due to malignant ureteral obstruction is an ominous sign of progressive disease, especially in pelvic malignancies. The mean survival rate of 12 months was less than 30%.

[Pain management for cancer patients with critical pathway on computer].

For relief from cancer pain, we developed critical pathway (CP) as an effective strategy for the medical staff treating cancer patients. This CP was made out of Microsoft Excel, and was used on personal computers. "Good sleeping" was set as the first goal and the second was "No pain in rest position." To achieve this, physicians and nurses evaluate medical efficacy and complications including nausea/vomiting, constipation, somnolence and hallucination everyday using controlled release oxycodone in addition to NSAIDs and prochlorperazine, stool softener and peristaltic stimulant for adverse effects. These outcomes lead to the medication change the next day by calculation using visual basic function due to opioid titration theory. In twelve patients this CP was acceptable, and all of them achieved the second goal within a week without severe adverse effects except constipation.