Chimiothérapie : Libre accès
Libre accès
ISSN: 2167-7700
ISSN: 2167-7700
Yunfei Hu, Weiwei Ouyang, Jing Zhang, Mengxiang Chen, Daoping Qing, Qiangxing Zeng, Ye Huang, Chunyan Hao, Rui Jia, Zhufeng Wu, Shaonan Ni, Yunhong Huang
Background: Compared with conventional mitoxantrone, liposomal mitoxantrone hydrochloride (PLM60) has shown promising antineoplastic effect and better safety profiles in the previous studies, and worth a further evaluation on its pharmacokinetic profiles.
Methods: In this single-center, open-label, randomized, parallel-group study, patients with histologically/cytologically confirmed relapse/refractory non-Hodgkin lymphoma (n=18) and Hodgkin lymphoma (n=6) were randomized to receive PLM60 12 mg/m2, 16 mg/m2 and 20 mg/m2 on day 1 of each 28-day cycle until the completion of 4 cycles treatment, disease progression, intolerable toxicities, or patient/investigator decision to withdraw (whichever occurred first). Blood samples were collected at prespecified timepoint and the primary endpoint was the pharmacokinetic parameters of total mitoxantrone and free mitoxantrone, the second endpoint was the incidence of adverse event and severe adverse event during the treatment, as well as Overall Response Rate (ORR) and Progression Free Survival (PFS) after PLM60 treatment.
Results: Of 32 patients screened, 24 patients were enrolled between July 28, 2019 and June 22, 2020. Cmax, AUC0-t and AUC0→∞ of total mitoxantrone and free mitoxantrone increased with the increasing doses, and both showed liner pharmacokinetics profiles. The ratio of mean AUC0-t and AUC0-∞ of free mitoxantrone to total mitoxantrone was 0.94%, 1.23%, 0.98% and 0.98%, 1.24%, 0.99%, separately. All the patients completed at least 1 cycle of treatment except that one patient in 12 mg/m2 group discontinued treatment due to hypersensitivity of which, 15 patients completed 4 cycles of treatment. All 24 patients experienced treatment related adverse events (TRAE). The most common (≥ 5%) TRAE was leucopenia, neutropenia, thrombocytopenia, anemia and skin hyperpigmentation. Leucopenia and neutropenia were grade 3 or 4 TRAE occurring ≥ 5% patients. After a median 5.6 month of follow- up, ORR and disease control rate of 24 patients was 41.7% (10/24, 95% CI, 22.1%-63.4%) and 62.5% (15/24, 95% CI, 40.6%-81.2%) respectively, with 2 patients achieving complete remission. Median PFS was 7.6 month (95% CI 3.2-NA).
Conclusion: After administering 12 mg/m2-20 mg/m2, PLM60 had a favorable pharmacokinetic profile as a liposomal preparation and showed preliminary efficacy in patients with relapse/refractory lymphoma with manageable safety.