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Background Olanzapine is an inexpensive and durable agent for the treatment of chemotherapy‐induced nausea and vomiting and is also superior to neurokinin‐1 receptor antagonists in the control of nausea. This study aimed to investigate the efficacy and safety of a low dose of 5 mg olanzapine plus granisetron and dexamethasone for treatment of carboplatin (CBDCA)‐induced nausea and vomiting in patients with thoracic malignancies. Materials and Methods We conducted a prospective, open‐label, single‐arm, multicenter, phase II trial in four centers in Japan. Registered patients were scheduled to receive area under the curve (AUC) ≥5 mg/mL per minute of CBDCA and had never received moderately to highly emetogenic chemotherapy. Patients received olanzapine 5 mg/day orally after supper for 4 days, in combination with granisetron and dexamethasone. Primary endpoint was complete response (CR; no emesis and no use of rescue medication) rate during the overall phase (0–120 hours). Results Between February 2018 and June 2020, 51 patients were enrolled, and 50 patients were evaluated. The CR rates in the overall (0–120 hours), acute (0–24 hours), and delayed phases (24–120 hours) were 94.0%, 100%, and 94.0%, respectively. No grade 3 or higher adverse effects of olanzapine were observed. Conclusion Prophylactic antiemetic therapy with a low dose of 5 mg olanzapine plus granisetron and dexamethasone showed durable efficacy with an acceptable safety profile. This three‐drug combination appears to be a reasonable treatment approach in patients with thoracic malignancies receiving an AUC ≥5 mg/mL per minute of CBDCA‐based regimen. Clinical trial identification number: UMIN000031267. Implications for Practice The results of this phase II trial indicated that the prophylactic administration of low‐dose of 5 mg olanzapine combined with granisetron and dexamethasone has promising activity with acceptable safety profile in patients with thoracic malignancy receiving high‐dose carboplatin chemotherapy., This article reports the results of a study that investigated the efficacy and safety of a three‐drug combination of low dose olanzapine combined with granisetron and dexamethasone in the treatment of chemotherapy‐induced nausea and vomiting in Japanese patients with thoracic malignancies treated with carboplatin.

Due to the increasing complexity of cancer chemotherapy and its associated supportive care, the role of clinical pharmacists in cancer chemotherapy is becoming increasingly more important. The present study evaluated the clinical interventions of a single pharmacist on the adverse events in hospitalized patients with thoracic cancer receiving cancer chemotherapy. A single-center, retrospective study was conducted at the 614-bed, tertiary care Gifu University Hospital. Hospitalized patients with thoracic cancer who received cancer chemotherapy in the respiratory medicine ward between April 2013 and May 2014 were enrolled. One of the two clinical pharmacists in charge was based in the respiratory medicine ward and implemented pharmaceutical care for the patients, including management of adverse events. Patient data were recorded in the electronic medical chart and retrospectively analyzed. A total of 445 patients with thoracic cancer received cancer chemotherapy in the respiratory medicine ward. A total of 152 interventions (101 patients) were performed by the clinical pharmacist prior to the administration of cancer chemotherapy, half of which comprised the addition of drugs to prevent adverse events. A total of 190 patients (39.4%) experienced grade ≥2 non-hematological or grade ≥3 hematological adverse events associated with cancer chemotherapy, and 223 medical interventions for relief of adverse events lowered the incidence of grade ≥2 non-hematological or grade ≥3 hematological adverse events to 17.8%. Of these, 45.3 and 7.5% of medical interventions for non-hematological and hematological adverse events, respectively, were implemented based on the pharmacist's recommendations. These findings revealed the marked contribution of a single clinical pharmacist in the respiratory medicine ward to the prevention and relief of adverse events in hospitalized patients with thoracic cancer receiving cancer chemotherapy.

Background Carboplatin (CBDCA) is known to exhibit a high emetic risk among moderate-emetic risk anticancer drugs, and the dose of CBDCA varies in different therapies. In concurrent chemoradiotherapy (CCRT) for non-small cell lung cancer (NSCLC), the weekly administration of CBDCA (area under the curve (AUC) 2 mg/ml/min) and paclitaxel (PTX: 40 mg/m2) is frequently applied as standard therapy. However, the optimal antiemetic measures in the use of such low-dose CBDCA remain unclear. In this study, we retrospectively assessed the antiemetic effect of a single-dose of a first-generation 5-hydroxytryptamine-3 receptor antagonist (5-HT3RA) and dexamethasone in the weekly CBDCA+PTX therapy in CCRT. Patients and methods The subjects were patients with NSCLC who were administered weekly CBDCA+PTX therapy in CCRT between January 2011 and December 2016 at our Department. As an antiemetic measure, a first-generation 5-HT3RA, azasetron (10 mg, orally) or granisetron (3 mg, intravenously), and dexamethasone (9.9 mg, intravenously) were administered on day 1. The patients were evaluated for the following efficacy end-points for the first cycle: Complete response (CR; defined as no vomiting or retching episodes with no rescue medication) in the acute phase (0-24 hours), delayed phase (>24-120 hours), and overall phase (0-120 hours). Other efficacy endpoints evaluated were no vomiting or retching, and no nausea in all phases. Results The subjects we assessed in this study were 46 patients who were administered weekly CBDCA+PTX therapy in CCRT. For the overall, acute, and delayed phases, the complete response rates were 89.1%, 100%, and 89.1%, respectively. The rate of no nausea in the overall, acute, and delayed phases was 78.3%, 100%, and 78.3%, respectively. The rate of no vomiting in the overall, acute, and delayed phases was 95.7%, 100%, and 95.7%, respectively. Conclusion A single dose of a first-generation 5-HT3RA and dexamethasone had a favorable suppressive effect on nausea and vomiting in weekly CBDCA+PTX therapy for NSCLC.

Antibodies targeting the receptor programmed death 1 on T cells have been approved for the treatment of lung cancer. Immune checkpoint inhibitors (ICIs) induce various immune-related adverse events. Life-threatening hematotoxicity can be provoked by ICI therapy. Although ICI-related endocrinopathy and interstitial lung disease have been well documented, hematotoxicity requiring intensive treatment is relatively rare. We describe a case of nivolumab induced thrombocytopenia after transient mild fever. A 77-year-old man with non-small cell lung cancer was administered nivolumab (240 mg/body, every 2 weeks) as second line therapy. On the day 2 after the first nivolumab infusion, he had a fever and his C-reactive protein level was elevated. Thoracic computed tomography revealed no interstitial lung disease or pneumonia. The fever resolved on day 9 and was not seen thereafter. On day 15 after the first nivolumab infusion, severe thrombocytopenia suddenly emerged. A bone marrow examination revealed no dysplasia or invasion. Based on the presence of high platelet-associated IgG titer, normal bone marrow plasticity and a lack of effectiveness of platelet infusion, we diagnosed nivolumab-induced immune thrombocytopenia. Daily administration of 60 mg of prednisolone restored the patient's platelet count and platelet-associated IgG. We also found that there was significant shrinkage of the primary lesion and that stable disease was achieved. One must be aware of this relatively rare side effect and the unusual clinical findings that could be associated with immunoreaction. Keywords: Immune checkpoint inhibitors, Nivolumab, Thrombocytopenia, Lung cancer, Immune-related adverse events, Platelet-associated IgG

Objectives Epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) represent the first-line treatment for patients with advanced EGFR mutation-positive non-small-cell lung cancer. Afatinib is a second-generation EGFR-TKI with excellent therapeutic effects. However, severe diarrhea and skin disorders are observed at high frequencies, often leading to treatment interruption because of low quality of life (QOL). The relationship between individual variations and the onset of these side effects remains to be elucidated. This study aimed to reveal the association among these side effects, pharmacokinetics, and related genetic polymorphisms. Materials and methods In total, 33 patients were recruited between July 2014 and June 2017. Afatinib plasma concentrations were measured at day 9 when the concentrations reached a steady state (early phase) and when the prescription dose was stable for more than 1 month (stable phase). We analyzed single nucleotide polymorphisms in the genes ATP-binding cassette sub-family B member 1 (ABCB1), ABCG2, and flavin-containing monooxygenase 3. Results The incidences of both diarrhea and acneiform eruption were greater than 80%. Afatinib plasma concentration and the severity of diarrhea in the early phase were correlated. Pharmacokinetics-related genetic polymorphisms influenced the severity of diarrhea. Particularly, the afatinib plasma concentration was higher and diarrhea was more severe in patients carrying the A allele of ABCG2 C421A. Onset of side effects, genetic polymorphisms, and diarrhea in the maintenance phase or acneiform eruption in the early or maintenance phases were not correlated. The severity of diarrhea is influenced by drug plasma concentrations in the early phase and genetic polymorphisms related to afatinib pharmacokinetics. Conclusion Particular genetic polymorphisms can be screened before afatinib administration and the dose adapted to individual patients can be controlled, leading to reduced side effects, improved QOL, and better patient compliance to maintain the therapeutic effects.

The G-CSF is used as a therapeutic drug of the febrile neutropenia in lung cancer chemotherapy, however, there were few reports that showed the effects of combination effects of G-CSF and anticancer drugs against lung cancer. In the present study, we investigated the effects of G-CSF and the combination effects of G-CSF and cisplatin on lung cancer growth. We investigated the effect of G-CSF against the LL-2 and KLN-205 cells by MTT assay and tried to detect the G-CSF receptor by RT-PCR. Next, to analyze the G-CSF effects in vivo, we transplanted the LL-2 into C57BL/6 mice, intraperitoneally administered G-CSF (30 micro/kg/day) with or without cisplatin (5 mg/kg), measured the tumor size and analyzed pathologically by HE and immunostaining. In vitro analyses, G-CSF showed no effects in LL-2 and KLN-205 cells, and RT-PCR revealed no G-CSF receptor mRNA. In vivo analyses, G-CSF alone did not significantly suppress tumor growth. However, concurrent G-CSF administration with cisplatin significantly enhanced the tumor suppressing effect of cisplatin in early stage of tumor growth. The analysis data of vWF immunostaining indicated that the neovascularization in the peripheral region of the tumors was more enhanced in G-CSF treatment mice. ELISA assay revealed that G-CSF did not influence the serum concentration of TNF-alpha and IL-12 in tumor-bearing mice. This study suggests that concurrent (combination) administration of cisplatin with G-CSF is a safe and effective method for enhancing anticancer effects and reducing chemotherapeutic agent-induced myelosuppression.

Background Endobronchial ultrasonography (EBUS) facilitates a lung cancer diagnosis. However, qualitative tissue characterization of lung tumors is difficult using EBUS. Integrated backscatter (IBS) is an ultrasound technique that calculates the power of the ultrasound signal to characterize tissue components in coronary arteries. We hypothesized that qualitative diagnosis of lung tumors is possible using the IBS technique. The aim of the present study was to elucidate whether the IBS technique can be used in lung tissue diagnoses. Methods Thirty-five consecutive patients who underwent surgery for lung cancer were prospectively enrolled. Surgical specimens of the lung and the tumor tissue were obtained, and the IBS values were measured within 48 h after surgery. Histologic images of lung and tumor tissues were compared with IBS values, and the relative interstitial area according to results of Masson’s trichrome staining were determined by using an imaging processor. Results The IBS values in tumor tissue were significantly lower than those in normal lung tissue (–50.9 ± 2.6 dB and –47.6 ± 2.6 dB, respectively; P P r = 0.53 and r = 0.67; P Conclusions Qualitative diagnosis of lung tumors was possible, with a sensitivity of 84% and a specificity of 85%, using the ultrasound IBS technique.

A population pharmacokinetic analysis was performed to investigate the pharmacokinetics of moxifloxacin (400 mg) following a once-daily oral administration in 28 patients with respiratory tract infection disease. The maximum plasma concentration and the area under the plasma concentration–time curve were 3.97 µg/ml and 51.74 µg·h/ml, respectively; these values were nearly equivalent to those of healthy adult men. Two adverse drug reactions (nausea, vomiting) occurred, but both reactions were mild and nonserious and the patients recovered without treatment. The pharmacokinetic profile of moxifloxacin in Japanese patients with respiratory tract infection and an underlying disease should thus be considered safe and comparable with that in healthy adult men, and adjustment of dose may do not need for age, sex, body weight, or renal function.

IntroductionAdding neurokinin-1 receptor antagonist (NK1RA) to 5-hydroxytryptamine-3 receptor antagonist and dexamethasone (DEX) improved carboplatin (CBDCA)-induced chemotherapy-induced nausea and vomiting (CINV) in patients with thoracic cancer. NK1RAs with high-drug cost are raising medical expenses. Olanzapine (OLZ) is less expensive and can be expected to have an excellent effect on CINV. This phase II trial aimed at evaluating the efficacy and safety of 5 mg OLZ plus granisetron (GRN) and DEX in CBDCA combination therapy with area under curve (AUC) ≥5 mg/mL/min for the prevention of nausea and vomiting in patients with thoracic cancer.Methods and analysisThis is an open-label, single-arm, multicentre, phase II trial. Patients who receive CBDCA-based therapies (AUC ≥5) and have never been administered moderate to high emetogenic chemotherapy will be enrolled. All patients will receive a combination of GRN, DEX and OLZ. The primary endpoint is complete response (CR) rate, defined as the absence of emetic episodes and no use of rescue medication for 120 hours after the initiation of CBDCA. Forty-eight patients are required based on our hypothesis that this regimen can improve CR rate from 65% (null hypothesis) to 80% (alternative hypothesis) with a one-sided type I error of 0.1 and a power of 0.8. We set the target sample size at 50 considering dropouts.Ethics and disseminationThe study protocol was approved by the institutional review board at each of the participating centres. Data will be presented at international conferences and published in peer-reviewed journals.Trial registration numberUMIN000031267.

A 78-year-old man presented with urinary retention and difficulty walking. Both legs showed muscle weakness, and he was experiencing lower body hypoesthesia. T2-weighted magnetic resonance imaging revealed lesions with high signal intensity and enhancement in the spinal cord and cerebrum. A cerebrospinal fluid specimen showed inflammatory changes, but negative cytology findings. Chest computed tomography revealed a tumor measuring 40 mm in diameter, and a lung biopsy revealed the presence of squamous cell carcinoma. We diagnosed the patient with paraneoplastic neurological syndrome related to lung cancer. The patient was treated with steroid pulse therapy and chemotherapy, which relieved the symptoms and enabled the patient to achieve an independent gait.

We investigated the efficacy and safety of albumin-bound paclitaxel (nab-PTX) and carboplatin (CBDCA) with concurrent radiotherapy for unresectable locally advanced non-small-cell lung cancer (NSCLC). Patients with Stage III NSCLC and an Eastern Cooperative Oncology Group performance status of 0 or 1 were eligible. Concurrent chemoradiotherapy consisted of weekly administration of nab-PTX (40 mg/m(2)) plus CBDCA (area under the plasma concentration time curve (AUC) 2) and thoracic radiotherapy (60 Gy/30 fractions) for a total of 6 weeks. After concurrent chemoradiotherapy, patients received an additional two cycles of consolidation phase chemotherapy that consisted of 4-week cycles of nab-PTX (100 mg/m(2) on Days 1, 8 and 15)/CBDCA (AUC 5 mg/ml/min on Day 1). Response was evaluated in accordance with the Response Evaluation Criteria in Solid Tumors. Progression-free survival and overall survival were estimated using the Kaplan-Meier method. Toxicity was graded using the National Cancer Institute Common Terminology Criteria for Adverse Events. A total of 10 patients were enrolled in this trial between September 2013 and January 2014 from three institutes. The overall response rate was 40.0% and the median progression-free survival was 6.7 months. Treatment-related death occurred in two patients. Grade 2 or worse severe radiation pneumonitis was observed in all three patients that had the volume of lung receiving at least 20 Gy (V20) >30%. The results of this study indicate that no further investigation is warranted into nab-PTX and CBDCA with concurrent thoracic radiation for Stage III NSCLC with V20 > 30% due to severe toxicity.