A Phase I Dose-Escalation Study of Lobaplatin Combined with Paclitaxel in Platinum-Sensitive Recurrent Ovarian Epithelial Carcinoma: Safety, Tolerability, and Preliminary Efficacy Analysis

Background : Platinum-Sensitive Recurrent Ovarian Epithelial Carcinoma (PSROC) is challenging to treat due to cumulative toxicity and resistance to platinum rechallenge. Lobaplatin (LBP), a third-generation platinum agent, offers advantages such as lower nephrotoxicity and lack of cross-resistance with carboplatin. Methods : Twelve patients were entered to three LBP dose cohorts (25, 30, 35 mg/m²) and TAX fixed to 175 mg/m². MTD was established by the 3+3 escalation design based on the occurrence of dose-limiting toxicities (DLTs) within Cycle 1. Safety evaluation was performed with CTCAE v5.0 criteria while pharmacokinetic (PK) analysis employed HPLC-MS/MS. Efficacy endpoints measured were objective response rate (ORR) in accordance with RECIST v1.1, progression-free survival (PFS), and overall survival (OS). Results : MTD was established at 30 mg/m² after two DLTs of Grade 4 neutropenia >7 days at 35 mg/m². The regimen had 50% ORR (1 CR, 5 PR) and 100% disease control rate. Median PFS was 7.0 months (95% CI:5.3-NA) with median OS of 21.7 months (95% CI:7.3-NA). Grade 3-4 hematologic toxicities were neutropenia (100%), thrombocytopenia (41.7%), and anemia (33.3%) that were manageable with supportive care. Non-hematologic toxicities were primarily Grade 1-2 (nausea/vomiting 25%, neuropathy 16.7%). PK analysis revealed dose-proportional exposure (AUC slope 1.02) and rapid renal clearance (68.5% of the dose excreted in urine in 24h). Conclusion : The LBP-TAX regimen shows promising efficacy and manageable toxicity in PSROC. The established MTD of 30 mg/m² supports future trials against standard platinum therapies.