Dexamethasone-sparing on days 2-4 with combined palonosetron, neurokinin-1 receptor antagonist, and olanzapine in cisplatin: a randomized phase III trial (SPARED Trial).

BACKGROUND: This study evaluated the non-inferiority of dexamethasone (DEX) on day 1, with sparing on days 2-4 in cisplatin-based chemotherapy. METHODS: Patients with malignant solid tumors who were treated with cisplatin (≥50 mg/m²) were randomly assigned (1:1) to receive either DEX on days 1-4 (Arm D4) or DEX on day 1 (Arm D1) plus palonosetron, NK-1 RA, and olanzapine (5 mg). The primary endpoint was complete response (CR) during the delayed (24-120 h) phase. The non-inferiority margin was set at -15%. RESULTS: A total of 281 patients were enrolled, 278 of whom were randomly assigned to Arm D4 (n = 139) or Arm D1 (n = 139). In 274 patients were included in the efficacy analysis, the rates of delayed CR in Arms D4 and D1 were 79.7% and 75.0%, respectively (risk difference -4.1%; 95% CI -14.1%-6.0%, P = 0.023). However, patients in Arm D1 had significantly lower total control rates during the delayed and overall phases, and more frequent nausea and appetite loss. There were no significant between-arm differences in the quality of life. CONCLUSION: DEX-sparing is an alternative option for patients receiving cisplatin; however, this revised administration schedule should be applied on an individual basis after a comprehensive evaluation. CLINICAL TRIALS REGISTRY NUMBER: UMIN000032269.

Prevention of vasculitis and vascular pain by side route administration of vinorelbine: A case report.

A 49-year-old female with non-small-cell lung cancer was placed on adjuvant chemotherapy with vinorelbine (25 mg/m2: Day 1.8) and cisplatin (80 mg/m2: Day 1). The simultaneous intravenous infusion of vinorelbine from the side route and 500 mL of saline from the main route successfully prevented vasculitis and vascular pain.

Thyroid dysfunction with atezolizumab plus bevacizumab after lenvatinib in hepatocellular carcinoma: A case series.

Atezolizumab plus bevacizumab is the recommended first-line treatment for unresectable hepatocellular carcinoma, based on guidelines from the Barcelona Clinic Liver Cancer prognosis and treatment strategy. However, atezolizumab plus bevacizumab may be used after administration of lenvatinib. Here, we present four patients who developed thyroid dysfunction after second-line treatment with atezolizumab plus bevacizumab, but not after lenvatinib alone. The patients were treated with lenvatinib and/or atezolizumab plus bevacizumab for unresectable hepatocellular carcinoma at Showa University Northern Yokohama Hospital. Of patients treated with only lenvatinib or atezolizumab plus bevacizumab, 2/18 (11%) and 4/15 (27%) developed thyroid dysfunction, respectively. All four patients treated with atezolizumab plus bevacizumab after lenvatinib developed hypothyroidism after 2-14 doses of atezolizumab plus bevacizumab. Three patients developed Grade 2 symptoms and were treated with levothyroxine sodium. In patients with hepatocellular carcinoma, the incidence of thyroid dysfunction may be higher among patients treated with atezolizumab plus bevacizumab after lenvatinib than those treated with lenvatinib or atezolizumab plus bevacizumab alone.

Five cases of skin desquamation due to bevacizumab combined with docetaxel-carboplatin in ovarian cancer.

The standard of care for ovarian cancer chemotherapy is paclitaxel-carboplatin. In Stage III and Stage IV patients, the addition of bevacizumab has been reported to be effective, and bevacizumab combined with paclitaxel-carboplatin and bevacizumab combined with docetaxel-carboplatin are used. Patients who received bevacizumab combined with docetaxel-carboplatin experienced a high incidence of skin hardening followed by peeling. In patients treated with bevacizumab combined with docetaxel-carboplatin, we experienced a high incidence of post-sclerotic peeling of the skin, a symptom that is rarely seen with paclitaxel-carboplatin (TC), docetaxel-carboplatin (DC), or bevacizumab combined with paclitaxel-carboplatin, and has been reported in a few cases. Therefore, we investigated the actual situation of skin desquamation caused by bevacizumab combined with docetaxel-carboplatin. Thirty-one patients were included in the study, and their age (mean ± SD) was 62.9 ± 9.0. The breakdown of treatment was as follows: TC in nine patients, bevacizumab combined with paclitaxel-carboplatin in ten patients, DC in six patients, and bevacizumab combined with docetaxel-carboplatin in six patients. No number of patients with TC or bevacizumab combined with paclitaxel-carboplatin showed skin desquamation. One for DC, and five for bevacizumab combined with docetaxel-carboplatin. The five patients treated with bevacizumab combined with docetaxel-carboplatin improved with topical steroids and moisturizers, but symptoms repeatedly appeared after each course. Skin desquamation was more frequent in bevacizumab combined with docetaxel-carboplatin.

Safety of immune checkpoint inhibitors in non-small-cell lung cancer patients with idiopathic interstitial pneumonia: a matched case-control study.

PURPOSE: The immune checkpoint inhibitor nivolumab is commonly used for non-small-cell lung cancer treatment. Immune checkpoint inhibitors cause immune-related adverse events, including interstitial pneumonia. However, there are no studies on the risk factors for interstitial pneumonia exacerbation after immune checkpoint inhibitor administration in patients with a history of different types of interstitial pneumonia. Therefore, we aimed to investigate the risk factors for interstitial pneumonia exacerbation in patients with non-small-cell lung cancer and a history of interstitial pneumonia. We also aimed to explore differences in the risk of interstitial pneumonia exacerbation due to various types of interstitial pneumonia-idiopathic interstitial pneumonia, immune-related pneumonitis, and radiation pneumonitis. METHODS: Eleven patients with a history of interstitial pneumonia exacerbation following the administration of immune checkpoint inhibitor were included in the study. We performed 1:2 matching based on age and sex. Twenty-two patients whose interstitial pneumonia did not worsen after immune checkpoint inhibitor administration belonged to the control group. We calculated odds ratios for each factor in the patients and control subjects. RESULTS: The odds ratio of idiopathic interstitial pneumonia in the case group was 0.15 (95% confidence interval: 0.03-0.89) (p = 0.03). There were no significant differences in other factors, such as smoking history, pulmonary emphysema, and chronic obstructive pulmonary disease. CONCLUSION: The administration of immune checkpoint inhibitors in non-small-cell lung cancer patients with a history of idiopathic interstitial pneumonia might be a viable treatment option and have clinical benefits.

Effectiveness of corticosteroids on immune checkpoint inhibitor-induced interstitial pneumonia among patients with a history of interstitial pneumonia: A case series.

There are few reports on the effectiveness of corticosteroids for immune checkpoint inhibitor-induced interstitial pneumonia in patients with a history of interstitial pneumonia. We report on 10 non-small cell lung cancer patients with a history of interstitial pneumonia who experienced immune checkpoint inhibitor-induced interstitial pneumonia. The immune checkpoint inhibitor-induced interstitial pneumonia lasted for a median duration of 41.5 days (range = 22-127 days). Eight of the ten patients responded to corticosteroid monotherapy; one patient responded to corticosteroids and the immunosuppressant, tacrolimus; and one patient did not improve after corticosteroid treatment. In non-small cell lung cancer patients with a history of interstitial pneumonia, immune checkpoint inhibitor-induced interstitial pneumonia was generally responds to corticosteroids.

[Evaluation of the Tolerability of Gemcitabine and Cisplatin Combination Chemotherapy with a Small Quantity of Replacement Fluid for Biliary Tract Cancer].

Cisplatin therapy induces kidney injury as a side effect. Thus, replacement fluid must be administered to prevent kidney injury. In our hospital, we use a Gemcitabine and Cisplatin combination chemotherapy (GC) at a total volume of approximately 500 mL for biliary tract cancer. We investigated the safety of GC with a small amount of replacement fluid. As a result, no serious adverse events and renal injury occurred that required discontinuation of treatment. The median overall survival time was 260 d (95% confidence interval, 154-367 d). This study suggests that GC with a small amount of replacement fluid could be performed tolerability. But we need to be careful about choosing patients such as patients who can drink 1 L orally and patients who can be treated as outpatients.

A cross-sectional survey of methods for controling hand-foot syndrome in patients receiving capecitabine treatment.

Medical personnel actively provide patients taking capecitabine with information on the items to prevent and treat hand-foot syndrome (HFS). However, they are typically unable to ascertain the extent of patient compliance with the recommended items. Thus, the aim of the present study was to ascertain the association between patient compliance with preventative measures for HFS and the development of HFS. Subjects included 90 patients who were treated with a drug regimen that included capecitabine. Patients were treated at one of four facilities between July 2015 and January 2017. The main parameters studied were the extent to which items to prevent and treat HFS were (or were not) followed, and the associaiton between this extent and the development of HFS symptoms. A manual prepared by a pharmaceutical company that manufactures capecitabine describes 15 routine items to follow in order to prevent and treat HFS. The two activities patients most often performed were 'applying a moisturizer' (74.1%) and 'keeping one's skin clean (e.g., washing one's hands and feet)' (64.7%). The two activities patients least often performed were 'using sunscreen on exposed areas' (14.1%) and 'using soft insoles' (11.8%). Patients who performed more items to prevent and treat HFS were significantly less likely to develop symptoms of HFS (P=0.022). Based on these findings, it is recommended that medical personnel provide instructions to the patients regarding the specific items necessary to prevent and treat HFS, and to follow-up with the patients regarding their compliance, with an emphasis on the items they are less likely to take and on the instructions to avoid external irritants. Following these guidelines should lead to qualitative improvement in HFS management.

[Effect of the active adult learning/patient oriented clerkship on affective reaction of students ∼ from the results of student survey].

We have previously reported the efficacy of the Patient Oriented Clerkship (POC) in the clinical clerkship in Showa University Hospitals, by a trial with old four-year pharmacy program students. In the unique clerkship, each student has a patient in charge, and follows his/her clinical conditions throughout the rotation. The aim of the POC is that having the students learn spontaneously (Active Learning) and actively (Adult Learning) promoted by student's commitment and responsibility by communicating with patients and health professionals in a team. As the POC requires students both Active Learning and Adult Learning, we define the POC as Active Adult Learning (AAL). Having a patient in charge for each student gives them many opportunities to participate in the medical team and foster their problem solving skills. Our previous study eventually showed positive results of the POC in the one-month short clerkship in the four-year program. On the other hand, the effect of the unique hospital clerkship in the new six-year program is not known. We conducted a student survey to clarify the learning effect in the new six-year education system which was revised and 2.5 month clinical clerkship was scheduled according to the model core clerkship curriculum. This report is the first report to show a challenge of the AAL/POC clerkship in the new six-year pharmacy education program.