Pharmacovigilance Evaluation of Bendamustine-related Skin Disorders using the Japanese Adverse Drug Event Report Database.

PURPOSE: Bendamustine is used in hematologic malignancies such as non-Hodgkin lymphoma, chronic lymphocytic leukemia, and multiple myeloma. This study evaluated the association of bendamustine-related skin disorders using the Japanese Adverse Drug Event Report (JADER) database. METHODS: We identified and analyzed reports of skin disorders between April 2004 and November 2019 from the JADER database and calculated the reported odds ratios (RORs) using disproportionality analysis. Additionally, we analyzed the relationship between skin disorders related to bendamustine use and patient information (age and sex). RESULTS: The symptoms, ranked in order of decreasing strength of association with skin disorders, were infusion-related reaction (ROR=5.708), herpes zoster (ROR=4.658), hypersensitivity (ROR=3.271), and rash (ROR=1.472). Additionally, analysis of the relationships between rash related to bendamustine and sex or age showed significant relationships for female sex and age younger than 70 years (ROR=2.247 and 2.176, respectively). Meanwhile, analysis of the relationship between herpes zoster and sex showed a significantly stronger association for male than female sex (ROR=2.887). CONCLUSION: Our analysis of skin disorders related to bendamustine use reported in the spontaneous reporting system databases showed that the association of rash with bendamustine use was affected by sex (female) and age (younger than 70 years). Additionally, the association of herpes zoster with bendamustine was affected by sex (male). Bendamustine is an outpatient chemotherapy regimen, and so we recommend close monitoring of female patients or those younger than 70 years who experience rash-like symptoms and male patients who experience herpes zoster-like symptoms.

Risk Factors for Febrile Neutropenia Induced by Docetaxel Chemotherapy in Patients with Non-small Cell Lung Cancer.

We retrospectively obtained data of patient background and pretreatment characteristics from medical records and identified the predictive factors of febrile neutropenia (FN) in patients with non-small cell lung cancer (NSCLC) treated with docetaxel alone or in combination with the anti-vascular endothelial growth factor (VEGF) antibody bevacizumab. Patients were eligible for inclusion in the study if they were 20 years or older, diagnosed with NSCLC, and received docetaxel monotherapy alone or in combination with bevacizumab at the Department of Respiratory Medicine, Kobe City Medical Center General Hospital, between July 1, 2011, and March 31, 2018. Eighty-one patients with recurrent or advanced NSCLC were included. Multivariate stepwise logistic regression analysis with backward selection revealed that lower baseline Eastern Cooperative Oncology Group performance status (ECOG-PS) scores of 1 and 2 (odds ratio (OR), 5.098; 95% confidence interval (CI), 1.045-24.879, p = 0.021) and baseline platelet count below 18.8 × 104/µL (OR, 3.861; 95% CI, 1.211-12.311, p = 0.022) were significant factors influencing the FN occurrence rate. Our results demonstrated that ECOG-PS 1-2 and lower baseline platelet count were significant risk factors of FN in patients with NSCLC receiving docetaxel-based chemotherapy. Moreover, the combination of anti-VEGF antibodies and docetaxel might be associated with increased FN frequency. Despite the limitations of this study including its retrospective design, single-center site, and small sample size, baseline ECOG-PS score and platelet count may be regarded as important indices to identify patients for prophylactic granulocyte-colony stimulating factor (G-CSF) treatment before docetaxel-based chemotherapy.

Risk Factors for Skin Toxicities Associated with Bendamustine-Based Chemotherapy in Patients with Non-Hodgkin Lymphoma.

Bendamustine plays an especially important role as a treatment for non-Hodgkin lymphoma (NHL). However, patients administered bendamustine alone or in combination with rituximab (BR) may experience drug-associated skin toxicities that can profoundly impact their health-related QOL through both physical discomfort and psychological distress. Moreover, worsening skin symptoms may lead to dose reduction or termination in the management of cancer chemotherapy. We retrospectively investigated patient backgrounds and pretreatment characteristics from medical records of NHL patients treated with bendamustine alone or BR therapy and identified predictive factors for skin toxicities at the start of chemotherapy. Patients were eligible for the study if they were 20 years older, diagnosed with NHL, and received bendamustine alone or BR therapy at the Department of Hematology, Kobe City Medical Center General Hospital, between April 1, 2011, and March 31, 2018. This study included 95 patients with newly diagnosed or refractory or relapsed NHL. Multivariate stepwise logistic regression analysis with backward selection revealed that baseline non-prior chemotherapy (odds ratio (OR), 15.72; 95% confidence interval (CI), 4.24-83.13, p < 0.001) was a significant factor influencing the occurrence of skin toxicity. Our results demonstrated that non-prior chemotherapy was a significant risk factor for skin toxicities in patients with NHL receiving bendamustine alone or BR therapy. No patient experience serious side effects of grade 3 or higher and that bendamustine is very useful as a first-line treatment.