The clinical value of using chloroquine or hydroxychloroquine as autophagy inhibitors in the treatment of cancers: A systematic review and meta-analysis.
Level 1 - systematic review of randomized trials
Systematic review and meta-analysis of controlled clinical trials.
PubMed 30431566 · doi:10.1097/MD.0000000000012912
What was done
A systematic review and meta-analysis of clinical studies evaluating autophagy-inhibitor-based therapy in cancer. Investigators searched for clinical trials examining chloroquine or hydroxychloroquine combinations (gemcitabine, doxorubicin, radiation, temozolomide with radiation, or monotherapy) compared to therapy without autophagy inhibition. Extracted outcomes included relative risk (RR) of overall response rate (ORR), 6-month progression-free survival (PFS) rate, and 1-year overall survival (OS) rate.
What was found
Seven clinical trials totaling 293 patients were analyzed. Autophagy-inhibitor-based regimens were associated with: - ORR: RR 1.33 (95% CI: 0.95–1.86, P = .009; note that the reported 95% CI crosses 1.0 despite the reported p-value) - 6-month PFS rate: RR 1.72 (95% CI: 1.05–2.82, P = .000) - 1-year OS rate: RR 1.39 (95% CI: 1.11–1.75, P = .000)
Why it matters
This review provides preliminary pooled evidence that repurposing chloroquine or hydroxychloroquine to inhibit autophagy may enhance standard chemotherapy and radiation response in cancer patients.
Limits
The total sample size is small (7 trials, 293 patients). Regimens, cancer types, and comparator backbones were highly heterogeneous (ranging from radiation combinations to monotherapy). There is an apparent reporting inconsistency in the abstract between the ORR 95% confidence interval and its p-value. Safety and long-term outcomes were not reported in the abstract.
Cited by
- supports Chloroquine functions as an autophagy inhibitor and has been utilized in cancer therapeutics.