A phase I dose-escalation study of Lobaplatin combined with paclitaxel in platinum-sensitive recurrent ovarian epithelial carcinoma: preliminary safety and tolerability supporting clinical trial dosing

<b>Objective</b>: To establish the recommended dose (MTD) and assess the safety and tolerability of lobaplatin (LBP) combined with paclitaxel for subsequent clinical development in platinum-sensitive recurrent ovarian epithelial carcinoma (PSROC), with antitumor activity evaluated as an exploratory endpoint. <b>Methods</b>: Twelve patients were enrolled in three LBP dose cohorts (25, 30, 35 mg/m²), with paclitaxel administered at a fixed dose of 175 mg/m². MTD was established by a 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. Exploratory antitumor activity was assessed using objective response rate (ORR) per RECIST v1.1, progression-free survival (PFS), and overall survival (OS). <b>Results</b>: The MTD was established at 30 mg/m², following the occurrence of two DLTs (Grade 4 neutropenia lasting > 7 days) at the 35 mg/m² dose level. The regimen demonstrated a 50% ORR (1 CR, 5 PR) and a 100% disease control rate. Median PFS was 7.0 months (95% CI:5.3-NA) with a 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 demonstrated dose-proportional exposure (AUC slope 1.02) and rapid renal clearance, with 68.5% of the administered dose excreted in urine within 24 h. <b>Conclusion:</b> The LBP-TAX regimen demonstrated manageable toxicity and established an MTD of 30 mg/m² in PSROC. Observed antitumor activity in this small phase I cohort are exploratory and warrant confirmation in larger, appropriately powered studies. A Phase I Dose-Escalation Study of Lobaplatin Combined with Paclitaxel in Platinum-Sensitive Recurrent Ovarian Epithelial Carcinoma: Preliminary Safety and Tolerability Supporting Clinical Trial Dosing.