Efficacy and safety of ivermectin in patients with mild COVID-19 in Japan and Thailand.

BACKGROUND: Ivermectin is an antiparasitic drug administered to hundreds of millions of people worldwide. Fundamental research suggests that ivermectin is effective against coronavirus disease 2019 (COVID-19); therefore, we investigated the efficacy and safety of ivermectin as a COVID-19 treatment option. METHODS: This multi-regional (Japan and Thailand), multicenter, placebo-controlled, randomized, double-blind, parallel-group, Phase III study evaluated the efficacy and safety of ivermectin in patients with mild COVID-19 (IVERMILCO Study). The participants took a specified number of the investigational product (ivermectin or placebo) tablets of, adjusted to a dose of 0.3-0.4 mg/kg, orally on an empty stomach once daily for three days. The primary efficacy endpoint was the time at which clinical symptoms first showed an improving trend by 168 h after investigational product administration. RESULTS: A total of 1030 eligible participants were assigned to receive the investigational product; 502 participants received ivermectin and 527 participants received a placebo. The primary efficacy endpoint was approximately 96 h (approximately four days) for both ivermectin and placebo groups, which did not show statistically significant difference (stratified log-rank test, p = 0.61). The incidence of adverse events and adverse drug reactions did not show statistically significant differences between the ivermectin and placebo groups (chi-square test, p = 0.97, p = 0.59). CONCLUSIONS: The results show that ivermectin (0.3-0.4 mg/kg), as a treatment for patients with mild COVID-19, is ineffective; however, its safety has been confirmed for participants, including minor participants of 12 years or older (IVERMILCO Study ClinicalTrials.gov number, NCT05056883.).

[A Case of Lung Adenocarcinoma Presenting with Leptomeningeal Carcinomatosis Successfully Treated with Afatinib after Erlotinib-Induced Hepatotoxicity].

A 65-year-old man was diagnosed with leptomeningeal carcinomatosis based on the findings of cerebrospinal fluid cytology and magnetic resonance imaging(MRI).Treatment with erlotinib and bevacizumab was initiated, and partial improvement in consciousness and MRI findings were obtained.However, it was difficult to continue the treatment because of elevation in levels of liver enzymes and melena.We switched the treatment to afatinib monotherapy, and his consciousness improved immediately.Progression -free survival and overall survival from the initiation of the treatment with afatinib were 7 and 9.4 months, respectively. This clinical course suggests activity of afatinib for central nervous system lesions of EGFRmutated lung cancer.

[A Retrospective Study Analyzing the Clinical Course of Patients with Non-Small Cell Lung Cancer Receiving Local or Systemic Therapy after Post-Operative Recurrence].

BACKGROUND: While systemic therapy is one of the therapeutic options available for post-operative recurrence of non-small cell lung cancer, efficacy of local therapy for locoregional recurrence or limited metastatic lesions has also been reported. OBJECTIVE: We aimed to evaluate the clinical course of patients with post-operative recurrence(locoregional or limited metastatic lesion)after receiving local or systemic therapy. METHODS: Clinical data were retrospectively analyzed and survival duration was compared using the logrank test. RESULTS: A total of 22 patients were included. Median progression-free survival in patients receiving local therapy, systemic chemotherapy, or a combination of both therapies was 15.1 months, 6.3 months, and 13 months, respectively. Two patients receiving treatment with EGFR-TKI did not show disease progression at 41.3 months and 45.8 months(p=0.265). Median overall survivals in patients receiving local therapy, systemic chemotherapy, or a combination of both therapies were 26.5 months, 20 months, and 37.9 months, respectively(p=0.510). After the treatment, 6 patients showed regrowth of the recurrent lesion, 8 patients showed remote metastases, and 2 patients showed both regrowth of the recurrent lesion and remote metastases. CONCLUSION: Patients who received treatment including local therapy showed longer survival duration, but statistical significance was not detected. Our study suggested that regrowth of the recurrent lesion and remote metastases can be equally observed after treatment.

Relationship of the urine cortisol level with the performance status of patients with lung cancer: a retrospective study.

PURPOSE: Cortisol plays an important role in the physical status of patients with end-stage lung cancer, but the association of urine cortisol levels with TNM stage/performance status (PS) is unclear in patients with advanced lung cancer receiving chemotherapy. The objective of this study was to examine this association. METHODS: In this single-center, retrospective, observational study, cortisol concentrations in 24-h pooled urine from 22 patients with advanced lung cancer were measured over 2 days. The mean concentration in each patient was compared with PS, TNM stage, and serum sodium and potassium ion levels. RESULTS: The 24-h urine cortisol levels were higher in PS2 or PS3 cases compared to PS1 (p < 0.05) and increased proportionally with PS. Urine cortisol also increased in N2 or N3 cases compared to N1 (p < 0.01) and also increased in M1 cases (p < 0.05). Urine cortisol levels were negatively correlated with serum sodium (R = -0.49, p < 0.05) and had a tendency for a positive correlation with serum potassium (R = 0.40, p = 0.06). CONCLUSION: The 24-h urine cortisol level increased in patients with advanced lung cancer undergoing chemotherapy. Low serum levels of potassium and high levels of sodium may indicate relative adrenal insufficiency.

Going back to home to die: does it make a difference to patient survival?

BACKGROUND: Many patients wish to stay at home during the terminal stage of cancer. However, there is concern that medical care provided at home may negatively affect survival. This study therefore explored whether the survival duration differed between cancer patients who received inpatient care and those who received home care. METHODS: We retrospectively investigated the place of care/death and survival duration of 190 cancer patients after their referral to a palliative care consultation team in a Japanese general hospital between 2007 and 2012. The patients were classified into a hospital care group consisting of those who received palliative care in the hospital until death, and a home care group including patients who received palliative care at home from doctors in collaboration with the palliative care consultation team. Details of the place of care, survival duration, and patient characteristics (primary site, gender, age, history of chemotherapy, and performance status) were obtained from electronic medical records, and analyzed after propensity score matching in the place of care. RESULTS: Median survival adjusted for propensity score was significantly longer in the home care group (67.0 days, n = 69) than in the hospital care group (33.0 days, n = 69; P = 0.0013). Cox's proportional hazard analysis revealed that the place of care was a significant factor for survival following adjustment for covariates including performance status. CONCLUSIONS: This study suggests that the general concern that home care shortens the survival duration of patients is not based on evidence. A cohort study including more known prognostic factors is necessary to confirm the results.

[Efficacy and toxicity of pemetrexed monotherapy for previously untreated elderly patients with non-squamous cell lung cancer with wild-type(or unknown)EGFR status].

BACKGROUND: The efficacy of docetaxel, vinorelbine, or gemcitabine monotherapy in previously untreated elderly patients with non-small cell lung cancer has been reported.Pemetrexed monotherapy has shown clinically equivalent efficacy to docetaxel, a standard therapeutic option, in patients with previously treated non-small cell lung cancer and in those with a lower incidence of toxicity such as febrile neutropenia. OBJECTIVE: In the present study, we aimed to investigate the efficacy and toxicity of pemetrexed in previously untreated elderly patients with non-squamous cell lung cancer and compare the results with those of docetaxel, considered a standard chemotherapeutic agent. METHODS: We retrospectively reviewed the medical records of patients with non-squamous cell lung cancer with wild-type(or unknown)epidermal growth factor receptor status who received pemetrexed or docetaxel monotherapy as first-line chemotherapy. RESULTS: We analyzed 6 patients with lung adenocarcinoma in the pemetrexed group and 6 patients with lung adenocarcinoma in the docetaxel group. The median progression-free survival was 3.6 months for patients receiving pemetrexed and 3.1 months for those receiving docetaxel(p=0.45). The median overall survival was 14.8 months in the pemetrexed group and 10.9 months in the docetaxel group(p=0.36).Patients who received docetaxel were more likely to have grade 3 or 4 neutropenia and febrile neutropenia than those receiving pemetrexed.However, 2 patients who received pemetrexed showed grade 3 pneumonitis. CONCLUSION: Pemetrexed monotherapy is a promising treatment for previously untreated elderly patients with non-squamous cell lung cancer.

Neutralizing Antibody Levels and Epidemiological Characteristics of Patients with Breakthrough COVID-19 Infection in Toyama, Japan.

Breakthrough infection (BI) after coronavirus disease 2019 (COVID-19) vaccination has increased owing to the emergence of novel SARS-CoV-2 variants. In this study, we analyzed the epidemiological information and possession status of neutralizing antibodies in patients with BI using SARS-CoV-2 pseudotyped viruses. Analysis of 44 specimens from patients diagnosed with COVID-19 after two or more vaccinations showed high inhibition of infection by 90% or more against the Wuhan strain and the Alpha and Delta variants of pseudotyped viruses in 40 specimens. In contrast, almost no neutralizing activity was observed against the Omicron BA.1 variant. Many patients without neutralizing activity or BI were immunosuppressed. The results of this study show that contact with an infected person can result in BI, even when there are sufficient neutralizing antibodies in the blood. Thus, sufficient precautions must be taken to prevent infection even after vaccination.

[Synchronous pulmonary hamartoma and lung cancer in a young patient].

A 23-year-old man was admitted for examination of an abnormal shadow in the right lower lung field. A chest CT scan revealed a nodule in the right lower lobe and a calcified nodule in the right upper lobe. A diagnosis of lung adenocarcinoma in the right lower lobe was made by transbronchial cytology. After resection of the right lower lobe and partial resection of the nodule in the right upper lobe were performed, we diagnosed lung adenocarcinoma in the right lower lobe (pathological stage IIIA) and hamartoma in the right upper lobe. Although several authors have reported cases of synchronous pulmonary hamartoma and lung cancer, it is uncommon in young patients. Since patients with hamartoma could also have lung carcinoma, careful observation is needed.

[Two cases of pulmonary sarcomatoid carcinoma mimicking malignant mesothelioma].

We report 2 cases of pulmonary sarcomatoid carcinoma mimicking malignant mesothelioma. Case 1: A 69 year-old man presented, complaining of right chest pain. The chest X ray film and CT showed tumors in the right chest wall and pleura. Histological findings of specimens obtained from a percutaneous biopsy revealed spindle tumor cells, and the immunohistochemistry showed that the tumor cells were positive for CK-7, AE1/AE3, and vimentin and negative for calretinin, D2-40, and WT-1. We diagnosed pulmonary sarcomatoid carcinoma and started chemotherapy with carboplatin and paclitaxel, but it was ineffective. Case 2: A 68 year-old man was admitted complaining of general malaise. The chest X ray film and CT revealed tumors in the right chest wall. Histological findings showed necrosis and spindle tumor cells which were positive for AE1/AE3 and vimentin, and negative for calretinin, D2-40, and WT-1. We diagnosed pulmonary sarcomatoid carcinoma and started chemotherapy with carboplatin and paclitaxel. However the disease continued to progress and he died 2 months after admission. The pulmonary sarcomatoid carcinoma was reported to have spred to the pleural and chest wall. The present two cases showed prominent chest wall and pleural tumors with obscure primary lung tumors. Therefore, we needed to differentiate sarcomatoid carcinoma from malignant pleural mesothelioma.

[A case of sarcoidosis who showed rapid swelling of mediastinal and abdominal lymph nodes].

A 49-year-old woman noticed hoarseness and facial palsey three months prior to her visit to our hospital. Chest radiograph and CT scanning revealed bilateral mediastinal and hilar lymphadenopathy. Bronchofiberoptic biopsy showed sarcoidosis. Her symptoms improved under no treatment. However, she showed rapid increase of mediastinal and abdominal lymph nodes swelling and elevation of serum level of sIL-2R during observation. Therefore, we must discriminate sarcoidosis-lymphoma syndrome from exacerbation of sarcoidosis. Mediastinoscopic biopsy was conducted for diagnosis, and it revealed exacerbation of sarcoidosis. We reported this rare case of rapid increase of mediastinal and abdominal lymph node swelling due to sarcoidosis.

Relationship between Carnitine Pharmacokinetics and Fatigue in Patients Treated with Cisplatin-Containing Chemotherapy.

BACKGROUND: Approximately 70% of the patients who receive chemotherapy suffer from fatigue, which lowers their quality of life and also has a negative influence on therapeutic efficacy. Previous studies have suggested a relationship between blood carnitine levels and fatigue. We conducted a prospective observational study to examine the relationship between carnitine pharmacokinetics and chemotherapy-induced fatigue in patients receiving cancer chemotherapy regimens that include cisplatin. PATIENTS AND METHODS: 11 patients receiving chemotherapy including cisplatin (60-80 mg/m2) were included in the study. We performed 24-h urine collections and took blood samples on day 1 (before the initiation of chemotherapy) and days 2, 3, 4, and 8 in order to measure the carnitine concentrations in the serum and urine. These were compared with measures of self-reported fatigue. The primary endpoint was the change in self-reported fatigue subscales from baseline to day 8. RESULTS: Urinary carnitine concentrations differed significantly on days 2 and 3 (p = 0.003). The Functional Assessment of Chronic Illness Therapy-Fatigue scale version 4A score on day 8 indicated significantly higher levels of fatigue as compared to day 1 (p = 0.013). CONCLUSION: This study suggests that there is an association between urinary carnitine levels and self-reported fatigue.

Phase I/II study of tecemotide as immunotherapy in Japanese patients with unresectable stage III non-small cell lung cancer.

OBJECTIVES: Unresectable stage III NSCLC (non-small cell lung cancer) confers a poor prognosis and interest is growing in the use of immunotherapy to improve outcomes for patients with this disease. We investigated the safety and efficacy of maintenance tecemotide, a mucin 1 (MUC1)-specific agent that induces T-cell responses to MUC1, versus placebo in Japanese patients with stage III unresectable NSCLC and no disease progression after primary chemoradiotherapy. MATERIALS AND METHODS: Patients aged ≥20 years with unresectable stage III NSCLC, stable disease or clinical response after primary chemoradiotherapy and performance status ≤1, were recruited across 25 centers in Japan. Patients were randomized 2:1 to tecemotide (930µg as lipopeptide) or placebo subcutaneously once weekly for 8 weeks, then every 6 weeks until disease progression or treatment withdrawal. Cyclophosphamide 300mg/m2 (maximum dose 600mg) was given intravenously 3days before the first dose of tecemotide. The primary endpoint was overall survival (OS). Secondary endpoints were progression-free survival, time to progression, time to treatment failure and safety. RESULTS: The intent-to-treat population comprised 172 patients; 114 received tecemotide and 58 placebo. Baseline characteristics were comparable between treatment arms. Most patients (94%) received primary concurrent chemoradiotherapy. There was no apparent trend toward increased OS time with tecemotide over placebo (median 32.4 versus 32.2 months, hazard ratio 0.95, 95% confidence interval 0.61-1.48; P=0.83). No improvements in secondary efficacy endpoints were observed. The frequency of treatment-related adverse events was similar, and serious adverse event rates were the same in both arms. There were no new safety signals. CONCLUSIONS: These results do not support those from a randomized phase III study (START) of improved OS with tecemotide in the subgroup of patients treated with primary concurrent chemoradiotherapy.

[A case of intravascular lymphomatosis with no abnormal findings on chest computed tomography and with diffuse pulmonary uptake of 67Ga on scintigraphy].

A 45-year-old man was admitted to our hospital with high-grade fever uncontrolled by antipyretic drugs, and elevation of the serum LDH and sIL-2R levels, and decrease of diffusing capacity for carbon monoxide. Chest computed tomography (CT) showed no abnormal findings but 67Ga scintigraphy revealed diffuse pulmonary uptake. He was given a diagnosis of intravascular lymphomatosis (IVL) based on transbronchial lung biopsy (TBLB) and immunohistochemical analysis. The prognosis of IVL is generally bad, because antemortem diagnosis is difficult. In this case early TBLB enabled satisfactory curative effect of IVL.

Appetite Loss as an Adverse Effect During Treatment with EGFR-TKIs in Elderly Patients with Non-small Cell Lung Cancer.

AIM: We conducted a retrospective study to investigate the frequency of appetite loss during treatment with epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) in elderly patients, aged 75 years or older, with non-small cell lung cancer harboring EGFR gene mutations. PATIENTS AND METHODS: Data of a total of 64 patients, including 39 relatively young (hereinafter, younger) patients and 25 elderly patients were analyzed. RESULTS: Appetite loss of all grades (p=0.074) and of grade 3 or greater (p=0.030) was more frequently observed in elderly patients. Diarrhea and oral mucositis were also more frequent in elderly patients, although they did not reach statistical significance. No apparent differences were observed in the frequency of aspartate aminotransferase/ alanine aminotransferase elevation, skin rash or fatigue between the two patient groups. The median (95% confidence interval) progression-free survival times were 10.8 (6.6-16.4) months and 11.8 (4.4-20.3) months in the younger and elderly patient groups, respectively. CONCLUSION: Our findings suggest that appetite loss is a major adverse effect in elderly patients with non-small cell lung cancer receiving treatment with EGFR-TKIs.

Lactate dehydrogenase and body mass index are prognostic factors in patients with recurrent small cell lung cancer receiving amrubicin.

AIMS AND BACKGROUND: Amrubicin monotherapy can be an effective treatment option for patients with recurrent small cell lung cancer (SCLC). We conducted this retrospective study to investigate the prognostic factors in patients with recurrent SCLC receiving amrubicin monotherapy. METHODS: The associations between survival and clinical data, including the performance status, body mass index (BMI), plasma lactate dehydrogenase (LDH) level, and plasma neuron-specific enolase level, were evaluated in patients with recurrent SCLC, and a subset analysis of patients with platinum-resistant disease was conducted. RESULTS: In all, 37 patients were evaluated. The median survival from the date of initiation of amrubicin monotherapy was 9.1 months (95% confidence interval 4.7-12.0 months). Multivariate analysis using a Cox proportional hazard model identified the plasma LDH level (p = 0.049), BMI (p = 0.031), and platinum resistance (p = 0.032) as independent factors associated with survival. The same associations were also observed in the subset of patients with platinum-resistant disease. CONCLUSIONS: Our findings suggest that the plasma LDH level and BMI may be useful prognostic factors in patients with SCLC receiving amrubicin monotherapy, including patients with platinum-resistant disease.

A novel predictive factor for the onset time of docetaxel-induced onychopathy: a multicenter retrospective study.

BACKGROUND: Taxanes are known to cause onychopathy. Previous studies have reported the relationship between onychopathy and paclitaxel dosing intervals and cumulative doses. However, there are no studies of the predictive factors for docetaxel-induced nail changes. The present study used the drug accumulation rate (mg/m2/day) as a novel indicator and evaluated its usefulness for the prediction of onychopathy. METHODS: From January 2008 to December 2009, we examined patients who received docetaxel at the Toyama University Hospital and Tonami General Hospital to determine the time to onset of onychopathy, the accumulation rate, and the cumulative dose. We then divided the study subjects into two groups, and used Receiver Operating Characteristic (ROC) analysis to calculate a cut-off value. We evaluated both indicators as predictive factors for onychopathy using the log-rank test and Cox proportional hazards model. RESULTS: Ninety-five patients were included in the present study. The results of the log-rank test sub-analysis revealed that the median number of days until onychopathy onset was significantly shorter in patients with an accumulation rate greater than the cut-off (P = 0.009), and in those with a cumulative dose below the cut-off (P < 0.001). The hazard ratios for the accumulation rate and cumulative dose, evaluated using Cox proportional hazards regression analysis, were 1.44 (P = 0.036) and 0.99 (P < 0.001), respectively. CONCLUSIONS: The results of the present study indicated that the drug accumulation rate influenced the time to onset of docetaxel-induced onychopathy. TRIAL REGISTRATION: This study is not applicable for trial registration due to retrospective chart review without intervention.

Elevated levels of plasma lactate dehydrogenase is an unfavorable prognostic factor in patients with epidermal growth factor receptor mutation-positive non-small cell lung cancer, receiving treatment with gefitinib or erlotinib.

Treatment with epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) has been shown to prolong survival in patients with EGFR mutation-positive non-small cell lung cancer (NSCLC). The present study performed a retrospective analysis to investigate the association between the plasma lactate dehydrogenase (LDH) levels and survival in patients with EGFR mutation-positive NSCLC receiving treatment with EGFR-TKIs. The medical charts of patients with EGFR mutation-positive NSCLC who were receiving treatment with EGFR-TKIs at Toyama University Hospital between 2007 and 2014 were assessed. The data from 65 patients were included in the analysis. Patients with higher plasma LDH levels exhibited shorter progression-free survival (6.2 vs. 13.2 months; P<0.01) and overall survival (10.5 vs. 36.1 months; P<0.01) periods compared with patients with lower plasma LDH levels. A Cox proportional hazards model identified that the plasma LDH level was associated with the progression-free survival (P=0.05) and overall survival (P<0.01). An association was demonstrated between the pretreatment plasma LDH level and the survival in patients with EGFR mutation-positive NSCLC receiving treatment with EGFR-TKIs. Close observation is required in EGFR mutation-positive NSCLC patients exhibiting high plasma LDH levels following the initiation of treatment with EGFR-TKIs.

Some biochemical and histochemical properties of human liver serine dehydratase.

In rat, serine dehydratase (SDH) is abundant in the liver and known to be a gluconeogenic enzyme, while there is little information about the biochemical property of human liver serine dehydratase because of its low content and difficulty in obtaining fresh materials. To circumvent these problems, we purified recombinant enzyme from Escherichia coli, and compared some properties between human and rat liver serine dehydratases. Edman degradation showed that the N-terminal sequence of about 75% of human serine dehydratase starts from MetSTART-Met2-Ser3- and the rest from Ser3-, whereas the N-terminus of rat enzyme begins from the second codon of MetSTART-Ala2-. The heterogeneity of the purified preparation was totally confirmed by mass spectrometry. Accordingly, this observation in part fails to follow the general rule that the first Met is not removed when the side chain of the penultimate amino acid is bulky such as Met, Arg, Lys, etc. There existed the obvious differences in the local structures between the two enzymes as revealed by limited-proteolysis experiments using trypsin and Staphylococcus aureus V8 protease. The most prominent difference was found histochemically: expression of rat liver serine dehydratase is confined to the periportal region in which many enzymes involved in gluconeogenesis and urea cycle are known to coexist, whereas human liver serine dehydratase resides predominantly in the perivenous region. These findings provide an additional support to the previous notion suggested by physiological experiments that contribution of serine dehydratase to gluconeogenesis is negligible or little in human liver.

Facility-Related Factors Influencing the Place of Death and Home Care Rates for End-Stage Cancer Patients.

BACKGROUND: In Japan, palliative home care is subject to increasing demand from patients. However, the number of deaths at home is still not as high as that of palliative home care users. OBJECTIVE: This study aimed to clarify factors influencing the place of death and home care rates, involving end-stage cancer patients targeted for palliative care by a general home-visit nursing agency. METHODS: A total of 87 patients who had used palliative home nursing care services provided by the study facility within a 6-year period after its opening were studied. RESULTS: The numbers of deaths at home supported by family physicians and those in hospital after readmission were 70 and 17, respectively. The numbers of deaths at home using services provided by the study facility and nurses belonging to it time-dependently increased, revealing a strong correlation between them. Furthermore, the place of death and home care rates were closely associated with the mean duration of home nursing services and home visits in collaboration with family physicians in charge. CONCLUSION: These results suggest that it may be possible to increase the rate of home care for end-stage cancer patients and meet their desires regarding the place of death through approaches to establish trust-based relationships with them and their families, such as strengthening manpower in home-visit nursing agencies and promoting collaboration between visiting nurses and family physicians in charge during home visits.

Stability of octreotide acetate decreases in a sodium bisulfate concentration-dependent manner: compatibility study with morphine and metoclopramide injections.

PURPOSE: Sodium bisulfate is known to affect the stability of octreotide. However, the critical concentration of sodium bisulfate is not known. Therefore, we assessed the critical concentration of sodium bisulfate needed to preserve the stability of octreotide using actual drugs containing sodium bisulfate. METHODS: Although morphine and metoclopramide preparations are considered to be compatible with octreotide, some of their products are known to contain sodium bisulfate. Thus, octreotide was mixed with preparations of sodium bisulfate solutions at serial concentrations and morphine and metoclopramide preparations containing sodium bisulfate, and octreotide stability was then evaluated using high performance liquid chromatography. RESULTS: Octreotide concentrations decreased significantly at a sodium bisulfate concentration of 0.1 mg/mL or higher after 10 days when octreotide was mixed with sodium bisulfate solutions at various concentrations. A significant decrease in octreotide concentrations also occurred when it was mixed with morphine and metoclopramide preparations containing sodium bisulfate and stored for 10 days; however, slight decreases were observed in the mixture with both preparations and were within the clinically acceptable range for morphine preparations. CONCLUSIONS: These results indicate that the residual rate of octreotide decreases with time in a sodium bisulfate concentration-dependent manner when octreotide was mixed with morphine or metoclopramide. However, this incompatibility may be clinically acceptable when the final sodium bisulfate concentration is lower than 0.1 mg/mL and the mixed solution is used within 7 days.