A phase i and pharmacokinetic study of paclitaxel poliglumex and cisplatin in patients with advanced solid tumors

Purpose: Determine the toxicity, maximum tolerated dose (MTD), and pharmacokinetics of paclitaxel poliglumex (PPX; CT-2103) in combination with cisplatin administered every 3 weeks. Patients and methods: Forty-three patients with advanced solid tumors were treated at escalating doses of PPX with a fixed dose of cisplatin at 75 mg/m². Conjugated and unconjugated paclitaxel were measured in plasma and urine. Cisplatin, as total platinum content in urine, was also assayed. Results: Dose-limiting toxicities included neutropenia and neuropathy with a cycle 1 MTD of 210 mg/m². Conjugated taxanes had a prolonged half-life of >100 h. Nine patients had partial responses, and 19 had stable disease. Conclusions: PPX is a water-soluble paclitaxel-polymer conjugate with a prolonged half-life and a limited volume of distribution. PPX/cisplatin showed good activity in a refractory patient population; however, cumulative neuropathy was a significant issue at high doses, suggesting that a lower dose may be appropriate for prolonged therapy.