Abstract
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.
Original language | English (US) |
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Pages (from-to) | 903-910 |
Number of pages | 8 |
Journal | Cancer chemotherapy and pharmacology |
Volume | 63 |
Issue number | 5 |
DOIs | |
State | Published - Apr 2009 |
Keywords
- Chemotherapy
- Cisplatin
- Conjugated taxanes
- Neuropathy
- PPX
- Paclitaxel poliglumex