• Jaffer A Ajani, Chris Takimoto, Carlos R Becerra, Alejandro Silva, Luis Baez, Allen Cohn, Pierre Major, Makio Kamida, Kevie Feit, and Robert De Jager.
• M.D. Anderson Cancer Center, The University of Texas, 1515 Holcombe Boulevard, Box 426, Houston, TX, 77030, USA. jajani@mdanderson.org
• Invest New Drugs. 2005 Oct 1; 23 (5): 479-84.

PurposeTo 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 MethodsForty-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.ResultsThirty-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.ConclusionsDX-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.

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