Comparison of Anticancer Drug Toxicities: Paradigm Shift in Adverse Effect Profile

The inception of cancer treatment with chemotherapeutics began in the 1940s with nitrogen mustards that were initially employed as weapons in World War II. Since then, treatment options for different malignancies have evolved over the period of last seventy years. Until the late 1990s, all the chemotherapeutic agents were small molecule chemicals with a highly nonspecific and severe toxicity spectrum. With the landmark approval of rituximab in 1997, a new horizon has opened up for numerous therapeutic antibodies in solid and hematological cancers. Although this transition to large molecules improved the survival and quality of life of cancer patients, this has also coincided with the change in adverse effect patterns. Typically, the anticancer agents are fraught with multifarious adverse effects that negatively impact different organs of cancer patients, which ultimately aggravate their sufferings. In contrast to the small molecules, anticancer antibodies are more targeted toward cancer signaling pathways and exhibit fewer side effects than traditional small molecule chemotherapy treatments. Nevertheless, the interference with the immune system triggers serious inflammation- and infection-related adverse effects. The differences in drug disposition and interaction with human basal pathways contribute to this paradigm shift in adverse effect profile. It is critical that healthcare team members gain a thorough insight of the adverse effect differences between the agents discovered during the last twenty-five years and before. In this review, we summarized the general mechanisms and adverse effects of small and large molecule anticancer drugs that would further our understanding on the toxicity patterns of chemotherapeutic regimens.

Safety and adverse effect profile of colchicine in renal impairment: a systematic review of randomised trials

Introduction: Colchicine is an anti-inflammatory drug prescribed for numerous medical conditions. Side effects are frequently encountered, particularly gastrointestinal symptoms. Caution and dose reduction are advised in patients with renal impairment because of a presumed increased risk of side effects. This systematic review intends to summarise the available literature to define the adverse effect profile of colchicine used in patients with kidney disease. Methods: We conducted a systematic review of randomised clinical trials seeking to evaluate the association between renal impairment and colchicine toxicity. We limited our search to randomised studies in humans in the English language. We allowed colchicine prescribed for any duration, dose or indication. Results: Our literature search identified a total of 7707 records. Only a single randomised trial was ultimately identified as meeting the inclusion criteria and addressing our research question. In patients with renal impairment, colchicine was not associated with an increased risk of dialysis, time until dialysis, or the incidence of liver function test derangement. We found no data for adverse events such as leukopenia, thrombocytopenia or diarrhoea in the kidney disease subgroup. Data was sparse and of poor quality. Conclusion: It is widely recommended that colchicine dose be reduced in patients with renal impairment due to an increased risk of drug accumulation and side effects. In our study, we failed to identify any robust clinical research substantiating this association. This is the first systematic review of randomised trials to investigate this link. Further research is required before the safety and tolerability of colchicine in renal disease can be confirmed.