Hydroxychloroquine as an adjunct to chemotherapy in neoplastic diseases: a systematic review and meta-analysis of clinical outcomes and toxicity profiles meta-analysis

Abstract Background Hydroxychloroquine (HCQ), an antimalarial and immunomodulatory drug, has been investigated as an adjunct to chemotherapy owing to its capability to inhibit autophagy and potentially sensitize tumor cells to cytotoxic agents. Objective To assess the influence of adding hydroxychloroquine to standard chemotherapy in cases with neoplasia, with emphasis on treatment response, performance status, and adverse events. Methods A systematic review and meta-analysis have been done in line with reporting items for systematic reviews and meta-analyses (PRISMA) guidelines. Web of Science, PubMed, Scopus, and Cochrane Library were searched up to August 2025. Eligible investigations involved adult patients with malignancy treated with chemotherapy plus HCQ versus chemotherapy alone or placebo. Main findings Seven studies comprising 383 patients have been involved. The mean patient age was 57.4 years. HCQ addition did not significantly improve complete response (OR 0.46; 95% CI, 0.08–2.61), partial response (OR 0.75; ninety-five percent CI, 0.36–1.56), stable disease (OR 1.01; 95% CI, 0.42–2.46), progressive disease (OR 2.07; 95% CI, 0.91–4.73), or objective response (OR 0.67; 95%CI, 0.30–1.46). A significant variance has been detected in ECOG 1 status (OR 1.93; 95% CI, 1.10–3.40), while ECOG 0 and ECOG 2 showed no differences. Reported adverse events, including headache and nausea/vomiting, were comparable between groups. Conclusion Adding hydroxychloroquine to conventional chemotherapy did not improve response results in cancer cases, though an association with ECOG 1 performance status was noted. HCQ was generally well tolerated without additional toxicity. Further large-scale randomized studies are required to clarify its therapeutic role.