Introduction: Cancer remains a worldwide threat, having caused almost 10 million deaths in 2020. The American Cancer Society has identified both known and probable carcinogens, including commonly used drugs. The aim of this study is to describe the drugs most frequently reported in the occurrence of cancer.

Methods: Among all individual case safety reports (ICSRs) in the global pharmacovigilance database VigiBase, we searched for the 50 most reported drugs with an adverse drug reaction term belonging to the query “Malignant or unspecified tumors” until June 30, 2023. Then, we extracted the disproportionality measurement data, information component (IC), and reporting odds ratio (ROR) in order to assess a disproportionality signal.

Results: Among all ICSRs in VigiBase, 871,925 contained an ADR belonging to the SMQ “Malignant or unspecified tumors”. Ranitidine was the drug with the most reported ADRs related to cancer (N= 106,484), followed by lenalidomide (N= 13,466), and etanercept (N= 8,014). The drugs with the highest IC were ranitidine (IC= 5.2, 95% confidence interval (95% CI) = [5.2; 5.2]), pioglitazone (1,353 ICSRs, IC= 4.2, 95% CI = [4.2; 4.2]), and regorafenib (1,272 ICSRs, IC= 2.8, 95% CI = [2.8; 2.8]).

Discussion: Our results show that the main pharmacological mechanisms are associated with ranitidine (link with levels of N-nitrosodimethylamine in ranitidine-based drugs), gene-activating drugs (pioglitazone: link with agonist effects on PPAR-γ gene activation), various pharmacological families with immunosuppressive effects (protein kinase inhibitors, immunomodulators, azathioprine, etc.), certain types of protein kinase inhibitors whose oncogenic mechanisms remain unclear (regorafenib, sorafenib, imatinib, ibrutinib, etc..), and hormone antagonists (tamoxifen, letrozole). Special monitoring of patients exposed to these drugs may be required. Further studies are needed to assess the risk with certain drugs in this ranking.