Shi M, et al. – This phase I trial wanted to ascertain the first cycle dose–limiting toxicities (DLTs) and maximum tolerated dose (MTD) of polymeric micellar paclitaxel (PM-paclitaxel), as well as, to assess the safety, antitumor activity, and pharmacokinetic (PK) profile of PM–paclitaxel in patients with advanced malignancies. Without additional toxicity, PM–paclitaxel had high MTD and exhibited desirable antitumor activity. Moreover, 300 mg/m² was the recommended dose of PM paclitaxel for phase II study.

Methods

• Experts escalated the PM-paclitaxel dose from 175 mg/m² (level 1) to 435 mg/m² (level 5).
• For 3 h without premedication on day 1 of a 21-day cycle, PM-paclitaxel was intravenously administered to patients.

Results

• PM-paclitaxel was administered to eighteen patients with confirmed advanced malignancies.
• Grade 4 neutropenia (four patients) and grade 3 numbness (one patient) were included in DLT.
• The aforementioned symptoms occurred in one of the six patients who received 300 mg/m² (level 3) PM-paclitaxel and all three patients who were treated with 435 mg/m² PM-paclitaxel.
• They determined the MTD of PM-paclitaxel as 390 mg/m² (level 4).
• Acute hypersensitive reactions were not observed.
• In six of 18 patients (33.3%), partial response was observed, three of whom had prior exposure to paclitaxel chemotherapy.
• Indicating that PM-paclitaxel exhibits linear Pks, the peak concentration and area under the curve values of paclitaxel increased with increasing dosage.