Characteristics of taste alterations in people receiving taxane-based chemotherapy and their association with appetite, weight, and quality of life.

PURPOSE: There is limited evidence on the effect of chemotherapy-associated taste alteration. This study aimed to evaluate taste alteration characteristics in patients receiving taxane-based chemotherapy and investigate the association of taste alterations with appetite, weight, quality of life (QOL), and adverse events. METHODS: This cross-sectional study evaluated 100 patients receiving paclitaxel, docetaxel, or nab-paclitaxel as monotherapy or combination therapy. Taste alterations were evaluated using taste recognition thresholds and severity and symptom scales. Taste recognition thresholds, symptoms, appetite, weight, and adverse events were compared between patients with and without taste alterations, and logistic regression analysis was performed to identify risk factors. RESULTS: Of the 100 patients, 59% reported taste alterations. We found significantly elevated taste recognition thresholds (hypogeusia) for sweet, sour, and bitter tastes in the taste alteration group receiving nab-paclitaxel (p = 0.022, 0.020, and 0.039, respectively). The taste alteration group reported general taste alterations, decline in basic taste, and decreased appetite. Neither weight nor QOL was associated with taste alterations. Docetaxel therapy, previous chemotherapy, dry mouth, and peripheral neuropathy were significantly associated with taste alterations. CONCLUSIONS: Almost 60% of patients receiving taxane-based regimens, especially docetaxel, reported taste alterations. Taste alteration affected the patient's appetite but did not affect the weight or QOL. Docetaxel therapy, previous chemotherapy, dry mouth, and peripheral neuropathy were independent risk factors for taste alterations.

Lower response to trastuzumab emtansine in metastatic breast cancer patients with human epidermal growth factor receptor 2 immunohistochemistry score of 2 and fluorescence in situ hybridization positive compared with immunohistochemistry score of 3: a retrospective study.

Tumor human epidermal growth factor receptor 2 (HER2) status is defined by either protein expression using immunohistochemistry (IHC) or gene amplification using fluorescence in situ hybridization (FISH). Approximately 20% of HER2-positive breast cancer is HER2 IHC 2+/FISH-positive. Unlike trastuzumab, it has not been studied whether the response to trastuzumab emtansine (T-DM1) differs according to HER2-positive status. We retrospectively identified and reviewed medical records of all patients with HER2-positive advanced breast cancer (ABC) who received T-DM1 in our hospital from October 2013 to December 2016. We compared the objective response rate (ORR) and progression-free survival (PFS) between patients in the HER2 IHC 3+ group and those in the HER2 IHC 2+/FISH-positive group. A total of 39 patients (IHC 3+: n = 32; IHC 2+/FISH-positive: n = 7) were analyzed. Nineteen (48.7%), 13 (33.3%), and 29 (74.4%) patients had received at least one prior chemotherapy, more than three lines of chemotherapy, and prior pertuzumab for ABC, respectively. ORR was significantly higher in the IHC 3+ group than in the IHC 2+/FISH-positive group (53.3% vs. 0%, P = 0.024). Median PFS was 7.9 months in the IHC 3+ group versus 3.9 months in the IHC 2+/FISH-positive group (hazard ratio 0.68; 95% confidence interval 0.28-1.69, P = 0.408). Among the HER2-positive ABC patients treated with T-DM1, ORR was significantly worse in HER2 IHC 2+/FISH-positive than in HER2 IHC 3+ patients. Median PFS tended to be shorter in patients with HER2 IHC 2+/FISH-positive.

Association between chronic kidney disease and mortality in stage IV cancer.

BACKGROUND: Chronic kidney disease (CKD) is known to be associated with cancer mortality. However, no study has considered the well-known cancer prognostic factors, ECOG Performance Status (PS) and cancer treatment, as confounding factors. We assessed the independent relationship between CKD and cancer death in stage IV cancer patients. METHODS: In this retrospective observational study, we included stage IV cancer patients diagnosed from 2009 to 2014 in a single center. We collected baseline clinical and laboratory variables, and cancer-specific variables, and assessed the presence of CKD. Our primary outcome was all-cause mortality. The secondary outcome was cancer-specific mortality and site-specific cancer mortality. RESULTS: Among 961 eligible stage IV cancer patients (median age 69 years, 51.8% male), 150 patients had CKD. During follow-up (median 9.8 months), 638 patients died, of whom 526 patients died from cancer. After adjusting for prognostic variables, including ECOG PS and cancer treatment, all-cause mortality and cancer-specific mortality were significantly higher in CKD patients than in non-CKD patients (HR 1.41, 95% CI 1.13-1.77 and HR 1.43, 95% CI 1.12-1.83, respectively). In patients with breast and kidney and urinary tract cancers, CKD was associated with a significantly increased risk of death (HR 7.01, 95% CI 1.47-33.4 and HR 3.33, 95% CI 1.42-7.78, respectively). CONCLUSIONS: CKD at the time of stage IV cancer diagnosis was associated with all-cause mortality and cancer-specific mortality. Moreover, the association between CKD and cancer-specific death was site specific for breast cancer and kidney and urinary tract cancer.

Validation of the Japanese version of the barriers questionnaire II in cancer pain management: a cross-sectional study.

BACKGROUND: The Barriers Questionnaire II (BQ-II) was developed to assess barriers to effective pain management. In this study, we aimed to assess the reliability and validity of the newly developed Japanese version of the BQ-II (JBQ-II). METHODS: This study used a cross-sectional design. The study was conducted an ambulatory infusion center for cancer in a general hospital in Tokyo, Japan. Participants were 120 Japanese patients with cancer and 21 Japanese health professionals with experience in pain management. Cronbach's alpha coefficient was used to calculate reliability. Test-retest reliability was assessed with Spearman's intra-class correlation coefficient (ICC). Construct, criterion-related, and discriminant validity were assessed using information about pain management, daily life, mental health, and subjective health. RESULTS: The Cronbach's alpha was 0.90 for the JBQ-II, and all ICCs exceeded 0.70 (P < 0.01). Factor analysis showed the JBQ-II had a virtually identical structure to the BQ-II, and path analysis supported the JBQ-II constructs. The JBQ-II was weakly correlated with poor mental state (r = 0.36, P < 0.01). Patients' JBQ-II scores were significantly higher than health professionals' scores. CONCLUSION: The JBQ-II is a valid and reliable measure of patient-related barriers to pain management among Japanese adult patients with cancer.

A self-directed home yoga programme for women with breast cancer during chemotherapy: A feasibility study.

Recent studies suggest yoga as a promising approach for improving the cognitive function of cancer survivors. We studied whether a self-directed home yoga programme was feasible for patients with breast cancer who were undergoing chemotherapy. Participants' preferences for the type of yoga course and the clinical effects of the programme were also assessed. In this study, 18 women (mean age, 43.9 years) were enrolled (44.7% recruitment rate). Of the participants, 63.6% had stage II cancer and 71.4% received adjuvant chemotherapy. Favourable retention (86%), adherence (94.4%) and acceptability (96.5%) rates were determined. Most (94.4%) of the women practiced the home programme more than twice a week on average. The participants preferred to gradually increase the intensity of the exercises. We only observed improvements in the cognitive aspects of fatigue. No serious adverse events were encountered during the programme. This self-directed home yoga programme was safe and feasible for patients with breast cancer undergoing chemotherapy.

Copy number alteration is an independent prognostic biomarker in triple-negative breast cancer patients.

BACKGROUND: Next-generation sequencing (NGS) has enabled comprehensive genomic profiling to identify gene alterations that play important roles in cancer biology. However, the clinical significance of these genomic alterations in triple-negative breast cancer (TNBC) patients has not yet been fully elucidated. The aim of this study was to clarify the clinical significance of genomic profiling data, including copy number alterations (CNA) and tumor mutation burden (TMB), in TNBC patients. METHODS: A total of 47 patients with Stage I-III TNBC with genomic profiling of 435 known cancer genes by NGS were enrolled in this study. Disease-free survival (DFS) and overall survival (OS) were evaluated for their association to gene profiling data. RESULTS: CNA-high patients showed significantly worse DFS and OS than CNA-low patients (p = 0.0009, p = 0.0041, respectively). TMB was not associated with DFS or OS in TNBC patients. Patients with TP53 alterations showed a tendency of worse DFS (p = 0.0953) and significantly worse OS (p = 0.0338) compared with patients without TP53 alterations. Multivariable analysis including CNA and other clinicopathological parameters revealed that CNA was an independent prognostic factor for DFS (p = 0.0104) and OS (p = 0.0306). Finally, multivariable analysis also revealed the combination of CNA-high and TP53 alterations is an independent prognostic factor for DFS (p = 0.0005) and OS (p = 0.0023). CONCLUSIONS: We revealed that CNA, but not TMB, is significantly associated with DFS and OS in TNBC patients. The combination of CNA-high and TP53 alterations may be a promising biomarker that can inform beyond standard clinicopathologic factors to identify a subgroup of TNBC patients with significantly worse prognosis.

Complete remission in metastatic primary malignant melanoma of the esophagus with nivolumab: a case report.

BACKGROUND: Primary malignant melanoma of the esophagus is a rare form of mucosal melanoma with a poor prognosis. While immune checkpoint inhibitors have recently extended overall survival in metastatic melanoma, data on their effects on primary malignant melanoma of the esophagus are limited because of its rarity. Here, we report the first case of long-term complete remission of metastatic primary malignant melanoma of the esophagus after nivolumab monotherapy. CASE PRESENTATION: A 79-year-old Asian man with a history of prostate cancer, gallbladder cancer, deep vein thrombosis, hypertension, and diabetes mellitus presented with gross hematuria. Cystoscopy revealed a solitary tumor on the right posterior wall of the bladder, and transurethral resection of bladder tumor was performed. Pathology was consistent with metastatic melanoma. A pigmented submucosal tumor-like growth in the esophagus was discovered on esophagogastroduodenoscopy. Computed tomography showed widespread metastases. The patient was diagnosed as having primary malignant melanoma of the esophagus with metastases to the stomach, subcutaneous tissue, lung, bladder, pleura, and peritoneum. Complete remission was achieved after seven cycles of triweekly nivolumab monotherapy. While nivolumab was discontinued because of kidney injury, the patient has remained tumor-free for over 4 years without further treatment. CONCLUSION: Immune checkpoint inhibitors may have astonishing curative effects in selected populations. More research is warranted to identify factors that increase the likelihood of achieving complete remission in primary malignant melanoma of the esophagus as well as in other melanomas.

Dupilumab treatment ameliorates clinical and hematological symptoms, including blood eosinophilia, in patients with atopic dermatitis.

BACKGROUND: Atopic dermatitis (AD) is an allergic disease that affects individuals of various ages. Recently, the IL-4/13 inhibitor dupilumab has gained regulatory approval for clinical use in AD patients. Dupilumab has been reported to reduce several markers of AD, including the serum levels of thymus and activation-regulated chemokine (TARC/CCL17), blood lactate dehydrogenase (LDH), and serum total immunoglobulin E (IgE). METHODS: We retrospectively reviewed data from 40 AD patients who were treated with dupilumab. Eczema Area and Severity Index (EASI), Investigator's Global Assessment (IGA), body surface area (BSA) scores, TARC, LDH, total IgE, and eosinophil count in peripheral blood were assessed for a total of 32 weeks. RESULTS: The EASI, IGA, and BSA scores improved significantly with treatment, indicating a reduction in AD severity. Serum TARC and LDH levels also significantly decreased with treatment. Serum IgE levels were unchanged at 2 weeks of treatment but decreased significantly between 4 and 32 weeks. The number of eosinophils in the peripheral blood decreased at 4, 16, and 32 weeks after treatment initiation. CONCLUSIONS: Several studies have reported that serum TARC, LDH, and total IgE levels are reduced by dupilumab treatment. Our real-world data are the first to demonstrate a reduction in blood eosinophilia in patients who receive clinical treatment with dupilumab.

Falls and Functional Impairments in Breast Cancer Patients with Chemotherapy-Induced Peripheral Neuropathy.

OBJECTIVE: We investigated the incidence of falls and functional impairments in breast cancer patients with chemotherapy-induced peripheral neuropathy (CIPN). Additionally, we examined whether taxane-induced peripheral neuropathy was associated with the patients' falls and functional impairments. METHODS: We conducted a cross-sectional study including 88 patients with breast cancer who received taxane-based chemotherapy and were recognized as having peripheral neuropathy symptoms (Common Terminology Criteria for Adverse Events Grade ≥1). Patients completed the Functional Assessment of Cancer Therapy-Gynecologic Oncology Group-Neurotoxicity questionnaire for neuropathy and described falls from the onset of the taxane-based chemotherapy to the time of the survey. Functional impairments were defined using the Activities of Daily Living subsection of the Vulnerable Elder's Scale. Data were analyzed using descriptive statistics and logistic regression. RESULTS: Of the participants, 40.9% experienced falls and 38.4% reported functional impairments. Most falls occurred on flat ground. Bone fracture due to falls was observed in 11.4% of the participants. Logistic regression revealed that CIPN was not significantly associated with the reported incidence of falls. However, it was significantly associated with functional impairments (odds ratio, 6.415; 95% confidence interval: 1.271-32.379; P = 0.024). CONCLUSIONS: CIPN was associated with functional impairments, but not with the incidence of falls. Patients should be informed prior to the onset of anticancer therapy that CIPN is a risk factor for functional impairments.

Drug-induced hypersensitivity syndrome/drug reaction with eosinophilia and systemic symptoms due to lamotrigine differs from that due to other drugs.

Drug-induced hypersensitivity syndrome (DIHS), also referred to as drug reaction with eosinophilia and systemic symptoms (DRESS), is a multi-organ systemic drug reaction characterized by hematological abnormalities and reactivation of human herpesvirus-6 (HHV-6). DIHS/DRESS is typically associated with a limited number of drugs, such as the anticonvulsants. Our group has treated 12 patients for DIHS/DRESS due to lamotrigine (LTG), but their presentation differed from that of patients with DIHS/DRESS caused by other drugs. The aim of the present study was to identify significant differences between DIHS/DRESS caused by LTG versus other drugs. We retrospectively reviewed data of 12 patients with DIHS/DRESS caused by LTG and 32 patients with DIHS/DRESS due to other drugs. The increase in alanine aminotransferase level was significantly milder in the LTG group than the DIHS/DRESS group due to other drugs. The percentage of atypical lymphocytes in the blood during DIHS/DRESS was lower in the LTG group. Serum levels of lactate dehydrogenase and thymus and activation-regulated chemokine were also lower in the LTG group. There were fewer DIHS/DRESS patients with HHV-6 reactivation in the LTG group than in the group treated with other drugs. Lymphocyte transformation after DIHS/DRESS onset was faster in the LTG group. The two groups did not differ with respect to the interval from first drug intake to rash, white blood cell count, blood eosinophilia or DRESS score. There were no significant histopathological differences between the two groups. The features of LTG-associated DIHS/DRESS and DIHS/DRESS due to other drugs differ.

Dynamic changes in CD44v-positive cells after preoperative anti-HER2 therapy and its correlation with pathologic complete response in HER2-positive breast cancer.

Chemotherapy has been reported to increase the proportion of cancer stem cells (CSCs) and to promote epithelial-mesenchymal transition (EMT) phenotype changes. Anti-HER2 therapy may provide a strategy for eliminating CSC and EMT, which contribute to therapeutic resistance. No study has determined the changes in the quantity or characteristics of CSCs or circulating tumor cells (CTCs) with EMT phenotype during preoperative anti-HER2 therapy, and whether these changes correlate to response to dual anti-HER2 therapy. In a prospective clinical trial to evaluate pharmacodynamic biomarkers, 18 patients with operable primary HER2-positive breast cancer received dual anti-Her2 preoperative therapy with trastuzumab and lapatinib with paclitaxel. Proportions of tumor cells with CSC characteristics and EMT markers in CTC's were estimated at baseline, after 6 and 18 weeks of preoperative therapy to determine the quantitative cutoff value to predict pathologic complete response (pCR). Out of 18 patients, 8 (44%) had a pCR; 5 of these 8 patients (62%) were positive for CD44v at baseline and none were positive on the 6-week biopsy. In contrast, 6 of the 10 patients without pCR exhibited persistent levels, or enrichment of CD44v proportion and expression at 6 and 18 weeks (p=0.0128). Other biomarkers were not statistically significant predictors of pCR. Enrichment of CD44v-positive tumor cells after dual anti-HER2 therapy alone may predict poor response to dual anti-HER2 therapy plus chemotherapy.

Actionable gene alterations in an Asian population with triple-negative breast cancer.

PURPOSE: It has been suggested that the biological characteristics of breast cancer may differ among different geographic or ethnic populations. Indeed, triple-negative breast cancer (TNBC), the most lethal breast cancer subgroup, has been reported to show a higher incidence in Japan than in the US. However, most genomic studies of these tumors are from Western countries and the genomic landscape of TNBC in an Asian population has not been thoroughly investigated. Here, we sought to elucidate the geographic and ethnic diversity of breast cancer by examining actionable driver alterations in TNBC tumors from Japanese patients and comparing them with The Cancer Genome Atlas (TCGA) database, which gather data primarily from non-Asian patients. MATERIALS AND METHODS: We performed comprehensive genomic profiling, including an analysis of 435 known cancer genes on Japanese TNBC patients (N=53) and compared the results to independent data obtained from TCGA (N=123). RESULTS: Driver alterations were identified in 51 out of 53 Japanese patients (96%). Although the overall alteration spectrum of Japanese patients was similar to that of the TCGA, we found significant differences in the frequencies of alterations in MYC and PTK2. We identified three patients (5.7%) with a high tumor mutation burden, although no microsatellite instability was observed in any of the Japanese patients. Importantly, pathway analysis revealed that 66.0% (35/53) of Japanese patients, as well as 66.7% (82/123) of the TCGA cohort, had alterations in at least one actionable gene targetable by an FDA-approved drug. CONCLUSION: Our study identified actionable driver alterations in Japanese patients with TNBC, revealing new opportunities for targeted therapies in Asian patients.

Metabolic abnormalities associated with atypical antipsychotics: a case report and alert.

We report a case of a 29-year-old man with schizoaffective disorder in which diabetes mellitus and hypertriglyceridemia developed with quetiapine (Seroquels). We reviewed the literature on the relationship between antipsychotic therapy and development of metabolic disorders and found serious concerns. This case demonstrates the importance of a careful monitoring of glucose and other metabolic parameters in patients receiving atypical antipsychotics.

Mucin-poor and aggressive mucinous tubular and spindle cell carcinoma of the kidney: Two case reports.

Mucinous tubular and spindle cell carcinoma (MTSCC) is a relatively rare renal epithelial neoplasm. Although MTSCC is considered to be a low-grade and indolent neoplasm, aggressive cases have been recently reported. The present study discussed two additional cases of high-grade MTSCC causing multiple distant metastases with a fatal course. In case 1, a 71-year-old patient presented with hematuria and pyuria. Computed tomography (CT) scan of the right kidney revealed a mass lesion, for which partial nephrectomy was performed. However, a follow-up CT imaging revealed distant metastases in the liver, the paraaortic lymph nodes and the bone. Despite molecular targeted therapy and irradiation, the patient succumbed due to tumor progression. In case 2, a 64-year-old patient presented with an incidentally identified mass lesion in the right kidney. A laparoscopic nephrectomy was performed, and a follow-up CT imaging revealed metastases in the skin and lungs. The cytology of pleural effusion revealed pleuritis carcinomatosa. Histologically, both cases were diagnosed as mucin-poor MTSCC with high-grade transformation, which comprised uniform tumor cells primarily forming slender tubules. The tumors contained low- and high-grade regions. In addition, venous invasion and necrosis were observed. The tumor cells also demonstrated increased Ki-67 labeling indices and cellular tumor antigen p53 (p53) nuclear accumulation. High-grade transformation, large tumor size, necrosis, venous invasion, high Ki-67 labeling index and p53 nuclear accumulation are generally predictive findings for aggressive behavior of malignant tumors. In the current report, it was emphasized that MTSCC possesses a wide spectrum of clinicopathological features. Thus, careful postoperative investigation is required for MTSCC with high-grade elements due to its aggressive nature.

Patients' Perspectives on Creating a Personal Safety Net During Chemotherapy.

Nurses are critical to the physical management and psychological support of patients undergoing chemotherapy, which is a vulnerable time for many. This article presents the results of a qualitative study intended to explore the experience of Japanese patients with breast cancer during chemotherapy, including the finding that participants created personal safety nets in physical, emotional, and social contexts that helped them to gain confidence in their ability to exert control over their lives. Understanding each patient's personal safety net allows nurses to support their patients in maintaining and improving their function and well-being.

Poor efficacy of the phosphorylated high-molecular-weight neurofilament heavy subunit serum level, a biomarker of axonal damage, as a marker of chemotherapy-induced peripheral neuropathy.

The phosphorylated form of the high-molecular-weight neurofilament heavy subunit (pNF-H) is a major structural protein in axons. The pNF-H level is elevated in the serum of certain patients with central nervous disorders, including chemotherapy-induced cognitive impairment. The present study was conducted to elucidate the potential role of pNF-H as a marker of chemotherapy-induced peripheral neuropathy (CIPN). A total of 71 patients with early breast cancer in various stages of treatment (following 1, 3 or 7 cycles of chemotherapy, or a previous history of breast cancer chemotherapy) were assessed with a self-administered PainDETECT questionnaire [pain location, pain intensity on an 11-point numeric rating scale (NRS), and various pain qualities] and a single serum pNF-H measurement. Patients were divided into two groups based on the presence or absence of bilateral symmetric pain in the distal portions of the extremities [CIPN(+) or CIPN(-)]. The χ2 and Mann-Whitney tests were used for statistical analyses. Among the participants, only 8 patients complained of CIPN. Their pain intensity was 3.5±1.9 (mean ± standard deviation) compared with 1.5±1.8 in the CIPN(-) group (P<0.01). The NRS of numbness in the CIPN(+) group was significantly higher (2.4±1.4) than that of the CIPN(-) group (1.0±1.0). Increased pNF-H levels were observed in 37.5% of the CIPN(+) patients and in 23.8% of CIPN(-) patients (P=0.40). In conclusion, CIPN is observed in the most distal portions of the peripheral nerves that are composed of dendrites but not axons. Although serum pNF-H is a biomarker of axonal damage, it is not useful as a marker of CIPN.

Triciribine Phosphate Monohydrate, an AKT Inhibitor, Enhances Gemcitabine Activity in Pancreatic Cancer Cells.

BACKGROUND: Pancreatic cancer is a highly lethal cancer due to early metastasis and resistance to current chemotherapeutic agents. Abnormal protein kinase B (AKT) activation is an important mechanism of chemoresistance to gemcitabine, the most widely used agent in pancreatic cancer. MATERIAL AND METHODS: In the study, we tested the hypothesis that combining an AKT inhibitor with gemcitabine would augment anti-tumor activity. We treated human pancreatic cancer MiaPaCa-2 cells with gemcitabine and the AKT inhibitor triciribine, alone and in combination, and evaluated treatment effects using trypan blue assay, 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium (MTT) assay, and cell death enzyme-linked immunosorbant assay. Colorimetric data of MTT assay were computationally analyzed for synergism of the combination therapy by CalcuSyn2 (Biosoft, Great Shelford, Cambridge, UK). RESULTS: Both gemcitabine and triciribine inhibited cell growth in a dose-dependent manner. Triciribine synergistically enhanced the cytotoxic activity of gemcitabine. The combination index (CI) provides the synergistic, additive, or antagonistic effects of the two-drug combination. CI at the 50% effective dose at 1:500 ratio of gemcitabine to triciribine was 0.74, indicating the synergistic effect of the drugs. The combination treatment with the non-apoptotic dose of each agent distinctly induced apoptosis, with gemcitabine in combination with triciribine, synergistically inhibiting pancreatic cancer cell growth and inducing apoptosis. CONCLUSION: These findings support the use of triciribine to overcome activated AKT-mediated resistance of pancreatic cancer to gemcitabine.

Potential role of pNF-H, a biomarker of axonal damage in the central nervous system, as a predictive marker of chemotherapy-induced cognitive impairment.

PURPOSE: Chemotherapy-induced cognitive impairment (CICI) is a clinically significant problem. Previous studies using magnetic resonance imaging indicated structural changes in the cerebral white matter of patients with CICI. Phosphorylated neurofilament heavy subunit (pNF-H), a major structural protein in axons, was recently reported to be elevated in the serum of patients with some central nervous system disorders. We performed a cross-sectional analysis of neuropsychological test results and serum pNF-H levels in patients undergoing adjuvant chemotherapy for breast cancer. Our hypothesis was that CICI is accompanied by axonal damage that can be detected by elevated serum pNF-H levels. EXPERIMENTAL DESIGN: Seventy-six patients with early breast cancer in various phases of treatment (naïve to chemotherapy; after one, three, or seven cycles of chemotherapy; or with a history of chemotherapy) were assessed by self-administered neuropsychological tests and a single pNF-H measurement. The χ(2) and Mann-Whitney tests were used for statistical analysis. RESULTS: Increased pNF-H levels were observed in 28.8% of the patients who underwent chemotherapy, but in none of the chemotherapy-naïve patients or patients with a history of chemotherapy. The pNF-H-positive rate increased significantly in proportion to the number of chemotherapy cycles (one cycle, 5.0%; three cycles, 31.6%; seven cycles, 55.0%; P < 0.05). No significant differences in neuropsychological test results were observed among the groups. CONCLUSIONS: The serum pNF-H level in patients undergoing chemotherapy for breast cancer increased in a cumulative dose-dependent manner, suggesting its potential application as a biomarker of neural damage after chemotherapy.

Differential impact of fosaprepitant on infusion site adverse events between cisplatin- and anthracycline-based chemotherapy regimens.

BACKGROUND: Fosaprepitant may be associated with infusion site adverse events (AEs), and these adverse events possibly vary according to chemotherapy regimen. PATIENTS AND METHODS: 267 oncology patients who were administered anthracycline- or cisplatin-based regimens were retrospectively studied. Multivariate logistic regression was performed in stratified analyses to evaluate potential regimen-specific effects of fosaprepitant. RESULTS: 41.7% of patients administered fosaprepitant experienced infusion site AEs. On the other hand, only 10.9% of patients administered aprepitant experienced AEs. Multivariate analysis showed a statistically significant overall increased risk of infusion site reaction associated with fosaprepitant (p<0.001), but when evaluated separately according to chemotherapy regimen, this relationship appeared to be largely confined to patients receiving an anthracycline-based regimen (OR=12.95, 95%CI=5.74-29.20). No association was observed among patients on cisplatin-based regimens. A test for interaction was statistically significant (p=0.001). CONCLUSION: Fosaprepitant is associated with an elevated risk of infusion site reaction in patients receiving anthracyclines.

Vitamin E δ-tocotrienol augments the antitumor activity of gemcitabine and suppresses constitutive NF-κB activation in pancreatic cancer.

The NF-κB transcription factor functions as a crucial regulator of cell survival and chemoresistance in pancreatic cancer. Recent studies suggest that tocotrienols, which are the unsaturated forms of vitamin E, are a promising class of anticancer compounds that inhibit the growth and survival of many cancer cells, including pancreatic cancer. Here, we show that tocotrienols inhibited NF-κB activity and the survival of human pancreatic cancer cells in vitro and in vivo. Importantly, we found the bioactivity of the four natural tocotrienol compounds (α-, ß-, δ-, and γ-tocotrienol) to be directly related to their ability to suppress NF-κB activity in vitro and in vivo. The most bioactive tocotrienol for pancreatic cancer, δ-tocotrienol, significantly enhanced the efficacy of gemcitabine to inhibit pancreatic cancer growth and survival in vitro and in vivo. Moreover, we found that δ-tocotrienol augmentation of gemcitabine activity in pancreatic cancer cells and tumors is associated with significant suppression of NF-κB activity and the expression of NF-κB transcriptional targets (Bcl-X(L), X-linked inhibitor of apoptosis, and survivin). Our study represents the first comprehensive preclinical evaluation of the activity of natural vitamin E compounds in pancreatic cancer. Given these results, we are conducting a phase I trial of δ-tocotrienol in patients with pancreatic cancer using pancreatic tumor cell survival and NF-κB signaling components as intermediate biomarkers. Our data also support future clinical investigation of δ-tocotrienol to augment gemcitabine activity in pancreatic cancer.