Abstract
Purpose: To determine the anti-tumor activity DX-8951f when administered as a 30-minute infusion daily for 5 days every 3 weeks to patients with previously untreated metastatic gastric cancer, and to evaluate toxicities and pharmacokinetics (PK) of DX-8951f in this patient population. Patients and methods: Forty-one patients were enrolled. All had previously untreated metastatic gastric cancer. DX-8951f was administered until disease progression or unacceptable toxicity. Responses were assessed after every 2 courses using RECIST criteria. Results: Thirty-nine patients were evaluable. Two patients achieved a partial response (PR) and 18 achieved stable disease (SD), including five patients with unconfirmed PR. A total of 141 courses of therapy were delivered (median 3, range 1-10). The most common drug-related toxicity was neutropenia. Non-hematologic toxicities were mostly mild to moderate; the most common were nausea, vomiting and anorexia. Plasma concentrations of DX-8951 (the anhydrous form of DX-8951f) were well described using a linear 2-compartment PK model. All concentrations and dose events were simultaneously modeled and explained by the population PK model. There was no evidence of non-linearity in the elimination PK, auto-inhibition or induction of DX-8951 clearance over the five days of administration. Conclusions: DX-8951f had modest activity against metastatic gastric cancer and its PK was dose-proportional. The toxicity profile was predictable and manageable. Further development of this agent is warranted.
Original language | English (US) |
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Pages (from-to) | 479-484 |
Number of pages | 6 |
Journal | Investigational New Drugs |
Volume | 23 |
Issue number | 5 |
DOIs | |
State | Published - Oct 2005 |
Keywords
- Camptothecin
- DX-8951f
- Exatecan mesylate
- Gastric cancer
- Topoisomerase I
ASJC Scopus subject areas
- Oncology
- Pharmacology
- Pharmacology (medical)