Effectiveness and Safety of Common Non-Oncologic Pharmaceuticals in Cancer Management: A Systematic Review

Background. De novo anticancer drug development is lengthy, costly, and risky, motivating cautious evaluation of off-label use of common non-oncologic agents where mechanistic plausibility and clinical signals exist. Objectives. To synthesize the effectiveness and safety of frequently repurposed non-oncologic drug classes in oncology and to identify priorities for practice and research. Methods. A PRISMA-guided systematic review (2015–2025) screened titles/abstracts and full texts in duplicate, with standardized extraction and narrative/thematic synthesis. Records identified: 1,699; duplicates removed: 119; other removals (missing metadata): 33; records screened: 1,547; excluded at title/abstract: 956; reports sought: 591; not retrieved: 410; assessed for eligibility: 181; included: 181. Outcomes included OS, PFS/DFS, ORR, QoL, and CTCAE-graded toxicities. Results. Antihypertensives comprised the largest class, followed by antidiabetics, statins, anti-inflammatories/aspirin, antibiotics, antidepressants, and anthelmintics; lung, breast, colorectal, pancreatic, and ovarian cancers were most represented. Signals suggest possible benefit for overall survival and mortality, with limited and inconsistent evidence for PFS/DFS and ORR; QoL was rarely reported. Outcome definitions, progression ascertainment, censoring rules, exposure metrics (dose, duration, timing), and reporting completeness were heterogeneous, constraining meta-analytic pooling and causal inference. Conclusion. Generalized repurposing for oncology is not supported at this time beyond established non-oncologic indications. Biologically coherent, low-toxicity signals, most consistently for β-blockade and RAAS modulation, and more variably for metformin, statins, and aspirin, justify targeted, rigorously designed evaluation in prospective trials and robust observational emulations, with harmonized endpoints and systematic CTCAE capture. Equity-by-design, common data elements, preregistration, and data/code sharing are essential to accelerate credible, practice-informing evidence. Keywords: Non-Oncologic Agents, Effectiveness and Safety, Cancer Management