Carica Papaya Leaf Extract to Improve Chemotherapy-Induced Thrombocytopenia: A Phase III Triple-Blinded, Randomized, Placebo-Controlled, Multicentric Trial.

Abstract

Carica papaya leaf extract (CPLE) is known to increase platelet counts (PCs) in certain infections. Patients were randomly assigned in a 2:1 ratio to the CPLE or placebo arm and continued treatment until the PC improved to 75,000 × 10⁹/L or above, a platelet transfusion was required, or upto D+10. The primary outcome was to evaluate whether CPLE improves PC faster compared with placebo in a significant proportion of patients with a modified intention-to-treat protocol. Between March 2020 and October 2024, 219 patients were randomly assigned, of whom 198 patients (CPLE arm: 129; placebo arm: 69) were analyzed for outcomes. The primary end point with modified intention-to-treat analysis showed a statistically significant increase in PC to ≥75,000 × 10⁹/L in a greater proportion of patients by D+4 compared with placebo (59% <i>v</i> 44%; <i>P</i> = .042). The primary outcome of increasing PC >75,000 × 10⁹/L at D+4 was significantly improved by CPLE (83/129, 64% <i>v</i> 33/69, 48%; <i>P</i> = .034) compared with placebo as per protocol analysis. There was no grade 3 or grade 4 treatment-related adverse events associated with CPLE. About 43% of patients in the placebo arm versus 25% of patients in the CPLE arm needed dose reductions or delays in their subsequent chemotherapy treatment for patients with grade 2 chemotherapy-induced thrombocytopenia (CIT) at the baseline (<i>P</i> 0.033) and not significant in grade 3 CIT. CPLE is a potential therapeutic intervention to improve CIT faster and to a greater extent than placebo in this phase III randomized trial without any safety concerns. It could be potentially used as a secondary prophylaxis to maintain the chemotherapy intensity.