Safety and efficacy of tirapazamine as anti-cancer drug: a meta-analysis of randomized controlled trials

Abstract

Background: The benefits of achieving better response by adding tirapazamine, a specific hypoxic cancer cell killer to chemo and or radiotherapy is contradictory. This study aims at analyzing the efficacy and safety of tirapazamine, apart from understanding the reasons for its doubtful and inconsistent benefits.Methods: Electronic database search in PUBMED, EMBASE, Cochrane library was conducted using search term “tirapazamine”. Randomized or cross-over studies comparing effects of tirapazamine vs other active treatment or placebo in patients >18yrs with any type of cancers were included under analysis. Overall Survival rate was the primary outcome measure while the incidences of grade-3 and 4 adverse drug reactions were the secondary outcome measure. Inverse variance method and both random and fixed effect models were used in the analysis by RevMan 5.3 software.Results: Total six studies were eligible with 1034 patients included in the analysis. Tirapazamine failed to show significant effect on overall survival rate at the end of one year (HR: 0.96, 95% CI: 0.88, 1.05), two year (HR: 1.04, 95% CI: 0.98, 1.12), three year (HR: 1.01, 95% CI: 0.89, 1.15) and five year (HR: 0.97, 95% CI: 0.77, 1.23) compared to placebo group. There was a significantly higher incidence of muscle cramps (Risk Difference, RD: 0.06, 95% CI: 0.02, 0.11) and dermal adverse events (RD: 0.03, 95% CI: 0.01, 0.06) in tirapazamine group.Conclusions: With the available evidences from clinical trials and preclinical studies, use of tirapazamine may not be justifiable and so is to side line this drug as another failed drug.

High throughput microfluidic system with multiple oxygen levels for the study of hypoxia in tumor spheroids

“…While these results demonstrate the higher cytotoxicity of TPZ under hypoxia, they are in contrast with standard in vitro tests reporting up to ∼500fold cytotoxicity increase under hypoxia in cell suspensions [45]. As clinical data showed that TPZ is only mildly effective in achieving tumor cytotoxicity [14,68,69], the results presented here are more in line with in vivo data. Overall, our system has shown how these two mechanistically-different drugs result in significantly different cytotoxicity under oxygen conditioning.…”

Role of Tumor-Associated Macrophages in Cervical Cancer: Integrating Classical Perspectives with Recent Technological Advances

“…Hypoxia-targeting therapy methods involve direct delivery of oxygen to hypoxic area via nanoparticles, the normalization of tumor vasculature, or the modulation of the HIF signaling pathway [30]. In CC, Tirapazamine was investigated as a potential drug targeting hypoxia; however, clinical and preclinical studies did not demonstrate significant efficacy [102].…”