Evaluation of time-to-onset and outcome of cardiac adverse events related to pembrolizumab using post-marketing surveillance in Japanese patients.

BACKGROUND: Pembrolizumab has been widely used in patients since its release, but information on cardiac Adverse Events (AEs) related to pembrolizumab remains lacking, particularly in Japanese populations. OBJECTIVES: This study aims to evaluate time to onset, incidence rates, and outcomes for pembrolizumab-induced cardiac AEs in patients with cancer using the Japanese Adverse Drug Event Report database. METHODS: We analysed data for the period from April 2004 to March 2022. Data on cardiac AEs were extracted and relative risks of AEs were estimated using the reporting odds ratio. RESULTS: We analysed 2,021,907 reports and identified 15,306 reports of AEs caused by pembrolizumab. Of these, 399 cardiac AEs were associated with pembrolizumab. Signals were detected for six cardiac AEs: myocarditis, immune-mediated myocarditis, pericardial effusion, cardiac tamponade, pericarditis, and pericarditis malignant. A histogram of median times to onset showed occurrence from 33 (21-97) days for immune-mediated myocarditis to 138 (67-168) days for pericarditis malignant, but some cases occurred even more than 1 year after the start of administration. Among these, myocarditis was the most frequently reported (27.1%), with fatal cases also reported. CONCLUSION: This study focused on cardiac AEs caused by pembrolizumab as post-marketing AEs. Patients should be monitored not only at the time of administration, but also over time for signs of these AEs, especially myocarditis, as some patients may have serious outcomes.

Predictors for the Development of Thromboembolic Events in Cancer Patients Treated with Bevacizumab, Ramucirumab, and Aflibercept: A Single-Institution Retrospective Analysis.

INTRODUCTION: The risk of thromboembolic events developing limits the dose of antiangiogenic agents, thereby reducing their efficacy. This retrospective study therefore sought to identify predictors for the development of antiangiogenic agent-induced thromboembolic events and to elucidate whether differences in the likelihood of thromboembolic events exist between different antiangiogenic agents or cancer types, to guide future strategies for optimizing safety, efficacy, and quality of life in patients receiving chemotherapy. METHODS: This study retrospectively investigated 468 cancer patients who received chemotherapy with bevacizumab, ramucirumab, or aflibercept at our outpatient chemotherapy center between December 2016 and April 2022. Variables related to the development of thromboembolic events were extracted from the medical records, and multivariate logistic regression analysis was performed to identify predictors for the development of thromboembolic events. The Wilcoxon/Kruskal-Wallis test was used to detect significant differences between groups. RESULTS: Significant factors included serum albumin level (odds ratio [OR] = 0.363, 95% confidence interval [CI] = 0.193-0.685; p = 0.0017) and diabetes mellitus (OR = 5.356, 95% CI = 1.711-16.769; p = 0.0039). Renin-angiotensin system inhibitors (OR = 0.307) had low OR, although it was not significant. No difference in the development of thromboembolic events was evident between cancer types (p = 0.0781), but differences were identified between the three antiangiogenic agents (p = 0.0132). Ramucirumab was associated with a lower likelihood of thromboembolic events. CONCLUSION: Serum albumin level and diabetes mellitus were identified as significant predictors for the development of antiangiogenic agent-induced thromboembolic events. In addition, the likelihood of thromboembolic events did not differ between cancer types but differed between antiangiogenic agents.

Evaluation of Time to Onset and Outcome of Cardiac Adverse Events Associated with Nilotinib using Post-Marketing Surveillance.

INTRODUCTION: Cardiac adverse events (CAEs) have become a concern as serious adverse events (AEs) of nilotinib administration. No reports have described the incidence of CAEs associated with nilotinib in Japanese patients. Thus, we conducted this study to evaluate the risk of nilotinib-induced CAEs, time to onset, incidence rates, and post hoc outcomes using the Japanese Adverse Drug Event Report database. METHODS: We analysed data for the period between April 2004 and March 2022. Data on CAEs were extracted, and relative risk of AEs was estimated using the reporting odds ratio. RESULTS: We analysed 2,021,907 reports and identified 3,545 reports of AEs caused by nilotinib. Of these, 511 reports involved CAEs. Signals were detected for 19 CAEs. Of these, electrocardiogram QT prolonged was the most frequently reported (30.9%). Fatal outcomes were observed in eight AEs: cardiac failure, atrial fibrillation, acute myocardial infarction, pericardial effusion, myocardial infarction, cardiac arrest, pericarditis, and cardiac tamponade. Of these, acute myocardial infarction, myocardial infarction, pericarditis, and cardiac tamponade exhibited mortality rates >10%. A histogram of median times to onset showed nilotinib-associated AEs occurring 3-485 days after nilotinib administration. CONCLUSION: We focused on CAEs caused by nilotinib as post-marketing AEs. Some cases resulted in serious outcomes. Patients should be monitored for signs of onset of these AEs not only at the start of administration but for a long period of time.

Evaluation of Time to Onset and Outcome of Lung Adverse Events Related to Pembrolizumab Using Marketing Surveillance.

BACKGROUND: Pembrolizumab has been widely used in patients since its release, but detailed information on lung-specific adverse events (AEs) from post-marketing monitoring has not been reported. OBJECTIVES: This study was undertaken to determine the risk of pembrolizumab-induced lung AEs, time to onset, and post hoc outcomes using the Japanese Adverse Drug Event Report database. METHOD: We analyzed data for the period between April 2004 and March 2022. Data on lung AEs were extracted and the relative risks of AEs were estimated using reporting odds ratios. RESULTS: We analyzed 2,021,907 reports and identified 15,306 reports of AEs caused by pembrolizumab, including 3,004 lung AEs. Signals were detected for 14 lung AEs. Interstitial lung disease was the most frequently reported (62.3%) and included fatal cases. A histogram of median time to onset showed occurrence ranging from 2 to 73 days, but some cases of interstitial lung disease occurred after 2 years of administration. The AEs showing the highest fatality rates were interstitial lung disease, respiratory failure, and pneumonia aspiration. CONCLUSIONS: This study focused on lung AEs caused by pembrolizumab as post-marketing AEs. Some cases could potentially involve serious outcomes, so patients should be monitored for signs of AE onset not only at the start of administration but also over an extended period, especially for interstitial lung disease.

Evaluation of lung adverse events with nivolumab using the spontaneous reporting system in Japan.

This study was conducted to examine times to onset, incidence rates, and outcomes of nivolumab-induced lung adverse events (AEs), using the Japanese Adverse Drug Event Report database. We analysed data for the period between April 2004 and March 2021. Data on lung AEs were extracted, and relative risks of AEs were estimated using the reporting odds ratio. We analysed 5,273,115 reports and found 18,721 reports of nivolumab-related AEs, including 3084 lung AEs. Signals were detected for nine lung AEs: interstitial lung disease; pneumonitis; lung disorder; organising pneumonia; pleural effusion; pneumonia aspiration; pneumonia bacterial; radiation pneumonitis; and infectious pleural effusion. Among these, interstitial lung disease was the most frequently reported (68.7%) and included some fatal cases. A histogram of median times to onset showed AEs occurring from 34 to 79 days after the first dose, but some cases occurred even more than one year after starting administration. In conclusion, we focused on lung AEs caused by nivolumab as post-marketing AEs. Some cases could potentially involve serious outcomes, particularly in interstitial lung disease. Patients should be monitored for signs of the development of these AEs not only at the start of administration, but also over an extended time.

Evaluation of Cardiac Adverse Events with Ponatinib Using a Spontaneous Reporting Database.

INTRODUCTION: The efficacy of ponatinib was demonstrated in patients resistant or intolerant to prior BCR-ABL tyrosine kinase inhibitors. However, cardiac adverse events (CAEs) have become a concern as a serious side effect of ponatinib administration. No reports have described the incidence of CAEs associated with ponatinib in Japanese patients. Thus, this study aimed to determine the risk of ponatinib-induced CAEs, time to onset, and post hoc outcomes using the Japanese Adverse Drug Event Report database. METHODS: We analyzed data for the period between April 2004 and March 2021. Data on CAEs were extracted, and relative risk of AEs was estimated using the reporting odds ratio. RESULTS: We analyzed 1,772,494 reports and identified 1,152 reports of AEs caused by ponatinib. Of these, 163 CAEs were reportedly associated with ponatinib. Signals were detected for thirteen CAEs: hypertension, cardiac failure, acute cardiac failure, atrial fibrillation, increased blood pressure, coronary artery stenosis, myocardial infarction, angina pectoris, pulmonary hypertension, prolonged QT on electrocardiography, cardiomyopathy, cardiac dysfunction, and acute myocardial infarction. Among these, hypertension was the most frequently reported AE (27.6%). A histogram of times to onset showed occurrence from 4.5 to 150.5 days. DISCUSSION/CONCLUSION: Hypertension, cardiac failure, coronary artery stenosis, and myocardial infarction could potentially result in serious outcomes and some cases occurred earlier or even more than 1 year after starting administration. Patients should be monitored for signs of the onset of these AEs not only at the start of ponatinib administration but also over the longer term.

Risk Factors of Capecitabine-Induced Hand-Foot Syndrome: A Single-Institution, Retrospective Study.

INTRODUCTION: This retrospective study was conducted to identify risk factors for developing hand-foot syndrome (HFS) and to determine new strategies for improving quality of life (QoL) in patients undergoing chemotherapy. METHODS: Between April 2014 and August 2018, we enrolled 165 cancer patients at our outpatient chemotherapy center who were undergoing capecitabine chemotherapy. Variables related to the development of HFS were extracted from the clinical records of patients for use in regression analysis. HFS severity was assessed at the time of completing capecitabine chemotherapy. The degree of HFS was classified in accordance with the National Cancer Institute Common Terminology Criteria for Adverse Events version 5. Multivariate ordered logistic regression analysis was performed to identify risk factors for the development of HFS. RESULTS: Risk factors for the development of HFS included concomitant use of a renin-angiotensin system (RAS) inhibitor (odds ratio [OR] = 2.85, 95% confidence interval [CI] = 1.20-6.79; p = 0.018), body surface area (BSA) (high) (OR = 12.7, 95% CI = 2.29-70.94; p = 0.004), and albumin (low) (OR = 0.44, 95% CI = 0.20-0.96; p = 0.040). DISCUSSION/CONCLUSION: Concomitant use of RAS inhibitor, high BSA, and low albumin were identified as risk factors for the development of HFS. The identification of potential risk factors of HFS may assist in the development of strategies that can be used to improve QoL in patients receiving chemotherapy regimens that include capecitabine.

Evaluation of Cardiac Adverse Events with Nivolumab Using a Japanese Real-World Database.

BACKGROUND: Nivolumab has been used for the treatment of various types of cancers and has achieved improvements in overall survival. However, nivolumab can cause a variety of adverse events (AEs). Among these, cardiac-specific AEs have received little attention in clinical trials, despite their life-threatening potential. OBJECTIVE: The present study aimed to determine the risk of nivolumab-induced cardiac AEs, time to onset, incidence rates, and post hoc outcomes using the Japanese Adverse Drug Event Report database. METHODS: We analyzed data for the period between April 2004 and March 2021. Data on cardiac AEs were extracted and relative risk of AEs was estimated using the reporting odds ratio (ROR). RESULTS: We analyzed 1,772,494 reports and identified 18,721 reports of AEs caused by nivolumab. Of these, 409 reports involved cardiac AEs. Signals were detected for four cardiac AEs: myocarditis; pericardial effusion; pericarditis; and immune-mediated myocarditis. Among these, myocarditis was the most frequently reported (35.0%) and included fatal cases. A histogram of times to onset showed nivolumab-associated AEs occurring 41-127 days after starting administration, with outlier cases of myocarditis or pericardial effusion occurring after more than one year, both with catastrophic consequences. CONCLUSION: This study focused on cardiac AEs caused by nivolumab as post-marketing AEs. Myocarditis and pericardial effusion have been associated with some fatal cases after administration of nivolumab. Patients should be monitored for signs of onset for these AEs, not only at the start of administration, but also over an extended period after nivolumab administration.

Factors associated with non-response to naldemedine for opioid-induced constipation in cancer patients: A subgroup analysis.

BACKGROUND: Opioid-induced constipation (OIC) is one of the most common adverse events of opioid therapy and can severely reduce quality of life (QOL). Naldemedine is the orally available peripheral-acting µ-opioid receptor antagonist approved for OIC treatment. However in daily clinical practice, some cancer patients show insufficient control of OIC even while receiving naldemedine. OBJECTIVE: To identify factors associated with non-response to naldemedine in cancer patients. METHODS: This study retrospectively analyzed 127 cancer patients prescribed naldemedine at Seirei Hamamatsu General Hospital in Japan between November 2016 and June 2021. For the regression analysis of factors associated with OIC, variables were extracted manually from electronic medical records. Naldemedine had been prescribed by the attending physician after the presence of OIC had been defined with reference to Rome IV diagnostic criteria. Naldemedine was evaluated as "effective" in cases where the number of defecations increased at least once in the first 3 days after starting naldemedine. Multivariate logistic regression analysis was performed to identify factors associated with non-response to naldemedine. The data used were from the group of patients who received naldemedine in our previous study. RESULTS: Factors significantly associated with non-response to naldemedine included chemotherapy with taxanes within 1 month of evaluation of naldemedine effect (odds ratio [OR] = 0.063; 95% confidence interval [CI] = 0.007-0.568), and addition of or switching to naldemedine due to insufficient efficacy of prior laxatives (OR = 0.352, 95% CI = 0.129-0.966). CONCLUSION: The identification of factors associated with non-response to naldemedine prescribed for OIC may help improve QOL among cancer patients.

Evaluation of lung toxicity with bevacizumab using the spontaneous reporting database.

This study was undertaken to determine the risk of bevacizumab-induced lung toxicity, time to onset, and post hoc outcomes using the Japanese Adverse Drug Event Report database. We analysed data for the period between April 2004 and March 2021. Data on lung toxicities were extracted, and relative risk of adverse events (AEs) was estimated using the reporting odds ratio. We analysed 5,273,115 reports and identified 20,399 reports of AEs caused by bevacizumab. Of these, 1679 lung toxicities were reportedly associated with bevacizumab. Signals were detected for nine lung toxicities. A histogram of times to onset showed occurrence from 35 to 238 days, but some cases occurred even more than one year after the start of administration. Approximately 20% of AEs were thromboembolic events. Among these, pulmonary embolism was the most frequently reported and fatal cases were also reported. The AEs showing the highest fatality rates were pulmonary haemorrhage, pulmonary infarction, and pulmonary thrombosis. In conclusion, we focused on lung toxicities caused by bevacizumab as post-marketing AEs. Some cases could potentially result in serious outcomes, patients should be monitored for signs of onset of AEs not only at the start of administration, but also over a longer period of time.

Predictors for development of oxaliplatin-induced peripheral neuropathy in cancer patients as determined by ordered logistic regression analysis.

BACKGROUND: Oxaliplatin causes acute cold-induced neurotoxicity and chronic cumulative neuropathy, which can require dose modification and impacts quality of life. However, effective strategies for managing oxaliplatin-induced peripheral neuropathy (OIPN) among affected patients remain elusive. OBJECTIVE: This retrospective study aimed to identify predictors for the development of OIPN. METHODS: Participants comprised 322 cancer patients at our hospital who were receiving oxaliplatin between January 2017 and March 2021. For the regression analysis of factors associated with OIPN, variables were manually extracted from medical charts. The severity of OIPN was evaluated using the National Cancer Institute's Common Terminology Criteria for Adverse Events, version 5. Multivariate ordered logistic regression analysis was performed to identify predictors for the development of OIPN. Optimal cut-off thresholds were determined using receiver operating characteristic analysis. Values of P <0.05 (2-tailed) were considered significant. RESULTS: Significant risk factors identified included higher body mass index (BMI) (odds ratio [OR] = 1.06, 95% confidence interval [CI] = 1.00-1.12; P = 0.043), female sex (OR = 1.67, 95%CI = 1.06-2.61; P = 0.026) and higher total dosage (OR = 2.39, 95%CI = 1.67-3.42; P = < 0.0001). CONCLUSION: High BMI, female sex and high total dosage were identified as significant predictors for the development of OIPN.

Evaluation of lung adverse events with trastuzumab using the Japanese pharmacovigilance database.

The present study aimed to determine the risk of trastuzumab-induced lung toxicity, time to onset, and post hoc outcomes using the Japanese Adverse Drug Event Report database. We analyzed data for the period between April 2004 and March 2021. Data on lung toxicities were extracted, and relative risk of adverse events (AEs) was estimated using the reporting odds ratio. We analyzed 1,772,494 reports and identified 4362 reports of AEs caused by trastuzumab. Of these, 693 lung toxicities were reportedly associated with trastuzumab. Signals were detected for seven lung toxicities: interstitial lung disease, pulmonary edema, pleural effusion, lung disorder, acute pulmonary edema, pulmonary fibrosis, and radiation pneumonitis. Among these, interstitial lung disease was the most frequently reported (61.8%). A histogram of times to onset showed occurrence from 1 to 105 days, but some cases of interstitial lung disease occurred even more than one year after the start of administration. The AEs showing the highest fatality rates were interstitial lung disease, pulmonary fibrosis, and radiation pneumonitis. This study focused on lung toxicities caused by trastuzumab as post-marketing AEs. Some cases could potentially involve serious outcomes; therefore, patients should be monitored for signs of the onset of these AEs not only at the start of administration, but also over an extended period, especially for interstitial lung disease.

Predictors of the development of nab-paclitaxel-induced peripheral neuropathy in breast cancer patients: post hoc analysis of a prospective, phase II, self-controlled clinical trial.

In a previous study, we showed that cryotherapy and compression therapy have comparable efficacy in preventing nab-paclitaxel-induced peripheral neuropathy. However, even with cryotherapy or compression therapy, there were patients with National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 grade ≥ 2 and/or Patient Neurotoxicity Questionnaire (PNQ) grade ≥ D peripheral neuropathies. Therefore, this post hoc analysis was performed to identify predictors of nab-paclitaxel-induced peripheral neuropathy. The clinical data in this post hoc analysis were the data of 38 breast cancer patients receiving chemotherapy with nanoparticle albumin-bound paclitaxel (nab-PTX) at our outpatient chemotherapy center from August 2017 to March 2019. The number of patients was analyzed assuming that there were data for 76 hands. Variables related to the development of nab-PTX-induced peripheral neuropathy were used for regression analysis. Multivariate-ordered logistic regression analysis was performed to identify predictors for the development of nab-PTX-induced peripheral neuropathy. Significant factors included smoking history [odds ratio (OR) 4.64, 95% confidence interval (CI) 1.60-13.5; P = 0.0048] with neuropathy evaluated by CTCAE, body mass index (BMI) (OR 1.13, 95% CI 1.01-1.26; P = 0.039) with neuropathy evaluated by PNQ (sensory), and smoking history (OR 3.80, 95% CI 1.40-10.30; P = 0.0087) and age (OR 1.06, 95% CI 1.01-1.11; P = 0.012) with neuropathy evaluated by PNQ (motor). In conclusion, smoking history, BMI and age were identified as significant predictors of the development of nab-PTX-induced-peripheral neuropathy.

Risk factors for opioid-induced constipation in cancer patients: a single-institution, retrospective analysis.

PURPOSE: To identify risk factors for opioid-induced constipation (OIC). METHODS: This study retrospectively analyzed 175 advanced cancer patients who were receiving pain treatment with opioids and were newly prescribed laxatives for OIC at Seirei Hamamatsu General Hospital between November 2016 and June 2021. For the regression analysis of factors associated with OIC, variables were extracted manually from clinical records. The effect of newly prescribed laxatives for OIC was evaluated as "effective" in cases where the number of spontaneous bowel movements increased at least once in the first 3 days. The OIC was defined based on Rome IV diagnostic criteria. Multivariate logistic regression analysis was performed to identify risk factors for OIC. Optimal cutoff thresholds were determined using receiver operating characteristic analysis. Values of P < 0.05 (two-tailed) were considered significant. RESULTS: Significant factors identified included body mass index (BMI) (odds ratio [OR] = 0.141, 95% confidence interval [CI] = 0.027-0.733; P = 0.020), chemotherapy with taxane within 1 month of evaluation of laxative effect (OR = 0.255, 95% CI = 0.068-0.958; P = 0.043), use of naldemedine (OR = 2.791, 95% CI = 1.220-6.385; P = 0.015), and addition or switching due to insufficient prior laxatives (OR = 0.339, 95% CI = 0.143-0.800; P = 0.014). CONCLUSION: High BMI, chemotherapy including a taxane within 1 month of evaluation of laxative effect, no use of naldemedine, and addition or switching due to insufficient prior laxatives were identified as risk factors for OIC in advanced cancer patients with cancer pain.

Predictors for development of palbociclib-induced neutropenia in breast cancer patients as determined by ordered logistic regression analysis.

This retrospective study aimed to identify predictors for the development of palbociclib-induced neutropenia. This study retrospectively analysed 78 breast cancer patients who had received palbociclib at our hospital between January 2018 and May 2020. For the regression analysis of factors associated with palbociclib-induced neutropenia, variables were extracted manually from medical charts. The level of palbociclib-induced neutropenia was evaluated using the National Cancer Institute's Common Terminology Criteria for Adverse Events (version 5). Multivariate ordered logistic regression analysis was performed to identify predictors for the development of neutropenia. Optimal cut-off thresholds were determined using receiver operating characteristic (ROC) analysis. Values of P < 0.05 (2-tailed) were considered significant. Significant factors identified included concomitant use of statin (odds ratio [OR] = 0.104, 95% confidence interval [CI] = 0.018-0.598; P = 0.011) and body mass index (BMI) (OR = 1.118, 95% CI = 1.007-1.241; P = 0.037). ROC analysis revealed that neutropenia (grade 4) was more likely to occur with a BMI ≥ 22.3 kg/m2. In conclusion, no concomitant use of statins and high BMI were identified as significant predictors for the development of palbociclib-induced neutropenia.

Predictors for development of denosumab-induced hypocalcaemia in cancer patients with bone metastases determined by ordered logistic regression analysis.

This retrospective study was undertaken to identify predictors for the development of hypocalcaemia even with prophylactic administration of calcium and vitamin D, and to help guide future strategies to improve the safety, efficacy, and QOL of patients receiving denosumab. Between January 2016 and February 2020, a total of 327 advanced cancer patients at our hospital who were receiving denosumab were enrolled. Variables associated with the development of hypocalcaemia were extracted from the clinical records. The level of hypocalcaemia was evaluated using CTCAE version 5. Multivariate ordered logistic regression analysis was performed to identify predictors for the development of hypocalcaemia. Optimal cut off thresholds were determined using ROC analysis. Values of P < 0.05 (2-tailed) were considered significant. 54 patients have developed hypocalcemia (≥ Grade 1). Significant factors identified included concomitant use of vonoprazan [odds ratio (OR) = 3.74, 95% confidence interval (CI) 1.14-12.26; P = 0.030], dexamethasone (OR = 2.45, 95%CI 1.14-5.42; P = 0.022), pre-treatment levels of serum calcium (OR = 0.27, 95%CI 0.13-0.54; P < 0.001), ALP/100 (OR = 1.04, 95%CI 1.01-1.07; P = 0.003), and haemoglobin (OR = 0.79, 95%CI 0.68-0.93; P = 0.004). ROC curve analysis revealed that the threshold for pre-treatment levels of serum calcium was ≤ 9.3 mg/dL, ALP was ≥ 457 U/L, and haemoglobin was ≤ 10.4 g/dL. In conclusion, concomitant use of vonoprazan or dexamethasone, and pre-treatment levels of serum calcium (low), ALP (high) and haemoglobin (low) were identified as significant predictors for the development of denosumab-induced hypocalcaemia.

Predictive factors for the development of proteinuria in cancer patients treated with bevacizumab, ramucirumab, and aflibercept: a single-institution retrospective analysis.

The development of proteinuria restricts the dose of anti-angiogenic agents, thereby reducing their efficacy. Thus, this retrospective study was undertaken to identify predictive factors of the development of angiogenesis inhibitor-induced proteinuria, and to elucidate if there is a difference in the likelihood of proteinuria among anti-angiogenic agents or cancer types, to help guide future strategies to improve the safety, efficacy, and quality of life of patients receiving chemotherapy. Between April 2014 and February 2019, 124 cancer patients at our outpatient chemotherapy center who were receiving chemotherapy with bevacizumab, ramucirumab, or aflibercept were enrolled. Variables related to the development of proteinuria were extracted from the patients' clinical records and used for regression analysis. The level of the proteinuria was evaluated based on CTCAE version 5. Multivariate ordered logistic regression analysis was performed to identify predictive factors for the development of proteinuria. The Wilcoxon/Kruskal-Wallis test was used to identify significant differences between groups. Significant factors identified included systolic blood pressure (SBP) [odds ratio (OR) = 1.031, 95% confidence interval (CI) = 1.005-1.058; P = 0.0197], number of cycles (OR = 1.049, 95% CI = 1.018-1.082; P = 0.0019), and calcium channel blocker use (OR = 2.589, 95% CI = 1.090-6.146; P = 0.0311). There was no difference among the three anti-angiogenic agents (P = 0.4969) or among cancer types (P = 0.2726) in the likelihood of proteinuria. In conclusion, SBP, number of cycles, and calcium channel blocker use were identified as significant predictors of the development of angiogenesis inhibitor-induced proteinuria. There was no difference among the three anti-angiogenic agents or among cancer types.

Comparison of the efficacy of cryotherapy and compression therapy for preventing nanoparticle albumin-bound paclitaxel-induced peripheral neuropathy: A prospective self-controlled trial.

BACKGROUND: Recently, the efficacy of cryotherapy and compression therapy to prevent taxane-induced peripheral neuropathy has been reported. We prospectively compared the efficacy of cryotherapy using a frozen glove (FG) and compression therapy using a surgical glove (SG) to prevent nanoparticle albumin-bound paclitaxel (nab-PTX)-induced peripheral neuropathy. PATIENTS AND METHODS: Breast cancer patients who received 260 mg/m2 of nab-PTX were eligible to participate in this trial. Patients wore a FG on one hand (60 min) without changing and two SGs of the same size (i.e., one size smaller than the size that best fit their hand) on the other hand (90 min) during chemotherapy. Peripheral neuropathy was evaluated at each treatment cycle using Common Terminology Criteria for Adverse Events (CTCAE) version 4.0, the Patient Neurotoxicity Questionnaire (PNQ), and the Functional Assessment of Cancer Therapy-Taxane subscale. Temperatures at each fingertip in both groups were measured thermographically. RESULTS: Between August 2017 and March 2019, 43 patients were enrolled and 38 were evaluated. No cases showed discordance of peripheral neuropathy between each gloved group in cases of CTCAE ≥ grade 2. In cases of PNQ ≥ grade D, using the Nam equivalence test, the upper test (P = 0.0329) and lower test (P = 0.0052) both showed negative results in comparisons between each gloved group. Fingertip temperature was significantly lower in the FG group than in the SG group after treatment (P < 0.0001). CONCLUSIONS: It seems to be no difference in incidence of nab-PTX-induced peripheral neuropathy using either cryotherapy or compression therapy.

Predictive factors for taxane acute pain syndrome determined by ordered logistic regression analysis.

This retrospective study was undertaken to identify predictive factors for developing taxane acute pain syndrome (TAPS) and to determine new strategies for improving QoL in patients undergoing chemotherapy. Between November 2010 and May 2018, we enrolled 121 breast cancer patients at our outpatient chemotherapy center who were undergoing chemotherapy with nanoparticle albumin-bound paclitaxel (nab-PTX) every 3 weeks. Variables related to the development of TAPS were extracted from the patients' clinical records and used for regression analysis. The degree of TAPS was classified as grade 0 = not developed; grade 1 = developed but did not require analgesics; grade 2 = developed but alleviated by analgesics such as acetaminophen or non-steroidal anti-inflammatory drugs (NSAIDs); or grade 3 = syndrome developed, causing sleep problems or interfering with daily living activities, but not alleviated by analgesics such as acetaminophen or NSAIDs thus requiring opioids. Multivariate ordered logistic regression analysis was performed to identify predictive factors for the development of TAPS. Significant factors identified for the development of TAPS included dose of nab-PTX (odds ratio (OR) = 11.717, 95% confidence interval (CI) = 11.6161-11.8182; P = 0.0421) and the administration of dexamethasone for up to 3 days (OR = 0.133, 95% CI = 0.0235-0.7450; P = 0.0223). In conclusion, a high dose of nab-PTX and the lack of dexamethasone administration for up to 3 days were identified as significant predictors of the development of TAPS.

Predictive factors for the development of irinotecan-related cholinergic syndrome using ordered logistic regression analysis.

Cholinergic syndrome is an acute adverse reaction associated with irinotecan. Development of cholinergic syndrome can be ameliorated or prevented by administering various anticholinergics, including atropine sulfate or scopolamine butylbromide. Although many of the side effects are transient and non-life-threatening, their onset is painful and can lower a patient's quality of life (QoL). This retrospective study was performed to identify predictive factors of the development of irinotecan-related cholinergic syndrome in order to develop future strategies for improving the QoL of patients undergoing chemotherapy. We enrolled 150 cancer patients who underwent chemotherapy, which included irinotecan, in our outpatient chemotherapy center between October 2014 and January 2017. For regression analysis, variables related to the development of irinotecan-related cholinergic syndrome were extracted from the patient's clinical records. The degree of cholinergic syndrome was classified as follows: grade 0 = not developed; grade 1 = developed but did not require anticholinergic drugs; and grade 2 = developed and required anticholinergic drugs or stopping the chemotherapy due to cholinergic syndrome. Multivariate ordered logistic regression analysis was performed to identify predictive factors for the development of irinotecan-related cholinergic syndrome. Threshold measurements were determined using a receiver operating characteristic analysis (ROC) curve. Significant factors identified for the development of cholinergic syndrome included female sex [odds ratio (OR) 2.183, 95% confidence interval (CI) 1.010-4.717; P = 0.0471] and irinotecan dose (OR 1.014, 95% Cl 1.007-1.021; P = 0.0001). ROC curve analysis of the group likely to develop cholinergic syndrome indicated that the threshold for the irinotecan dose was 175 mg or above (area under the curve = 0.69). In conclusion, female sex and irinotecan dose were identified as significant predictors of the development of cholinergic syndrome.