Tumor lysis syndrome associated with bortezomib: A post-hoc analysis after signal detection using the US Food and Drug Administration Adverse Event Reporting System.

Tumor lysis syndrome (TLS) is a cancer chemotherapy-associated oncologic emergency. Although there have recently been substantial developments in cancer chemotherapy, these may increase the risk of TLS. In this study, we aimed to identify anticancer agents that increase TLS risk, as classified by a TLS panel consensus, using the US Food and Drug Administration Adverse Event Reporting System (FAERS) database. TLS reports were retrieved from the FAERS database, and reporting odds ratios (RORs) were used to estimate associations between TLS and old and new anticancer agents or their combinations. We identified 1615 TLS cases among 4 330 807 case reports covering the period from the first quarter of 2004 through to the first quarter of 2014. Using RORs, we detected significant risk signals for 56 of 64 anticancer agents (37 and 19 cytotoxic and molecular-targeted drugs, respectively). Bortezomib in particular was found to be associated with a high ROR and numerous TLS events relative to those of other molecular-targeted drugs (161 TLS events, ROR = 28.89, 95% confidence interval: 24.53-34.02). The main indication of bortezomib is multiple myeloma, a low-risk disease for TLS occurrence. We conducted a detailed analysis focusing on regimens containing bortezomib, lenalidomide, and thalidomide. Bortezomib-containing treatment regimens were more frequently associated with TLS events than were other multiple myeloma treatment regimens (cytotoxic chemotherapy, lenalidomide, and thalidomide). Although the risk of TLS in patients with multiple myeloma is generally considered low, a cautious evaluation of TLS risk is recommended for patients receiving bortezomib-containing therapy.

Hepatitis B infection reported with cancer chemotherapy: analyzing the US FDA Adverse Event Reporting System.

We conducted data mining using the US Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) database on spontaneously reported adverse events to evaluate the association between anticancer drug therapy and hepatitis B infection. Reports of hepatitis B infection were retrieved from the FAERS database. The reporting odds ratio (ROR) was used to estimate the association between hepatitis B infection and various anticancer agents and drug combinations. We detected statistically significant risk signals of hepatitis B for 33 of 64 anticancer agents by ROR (26 cytotoxicity drugs and seven molecular-targeted drugs). We focused on molecular-targeted drugs and assessed the risk of hepatitis B from specific anticancer drug combinations. The frequency of hepatitis B infection was significantly high for drugs such as rituximab, bortezomib, imatinib, and everolimus. The addition of cyclophosphamide, doxorubicin, and fludarabine to drug combinations additively enhanced the frequency of hepatitis B infection. There were no reports on hepatitis B infection associated with trastuzumab or azacitidine monotherapy. However, trastuzumab-containing regimens (e.g., combinations with docetaxel or paclitaxel) were correlated with the incidence of hepatitis B infection, similar to azacitidine monotherapy. Our findings suggest that the concomitant use of anticancer drugs, such as trastuzumab, taxane, and azacitidine, may contribute to the risk of hepatitis B infection. The unique signals detected from the public database might provide clues to eliminate the threat of HBV in oncology.