A phase I schedule optimization study of pegylated glutaminase (PEG-PGA) plus 6-diazo-5-oxo-l-norleucine (DON) in patients (pts) with advanced solid tumors.

3049 Background: DON is a glutamine antagonist and inhibits irreversibly the purine/pyrimidine synthesis. Effectiveness of DON is greatly enhanced if plasma glutamine is depleted by PEG-PGA. Previous phase I studies suggested twice weekly administration. Methods: Pts with refractory metastatic colorectal (mCRC) or non-small cell lung cancer (NSCLC) were enrolled. After a single initial dose (150 IU/m2) prior to day 1, PEG-PGA (150 IU/m2) was infused 30 minutes before DON (280-470 mg/m2). Both were given as 15 min i.v. infusions on day 1, 8 and 15 every 21 days until disease progression or unacceptable toxicity. DON was escalated in 3 pt cohorts until MTD was reached. Dose limiting toxicity (DLT) was assessed for the first 21 days. The objectives were: determination of the maximal tolerable dose (MTD), safety (NCI-CTC v2.0), pharmacodynamics and tumor response (RECIST 1.0). Results: Sixteen pts (4f/12m, 13 mCRC, 3 NSCLC, median age 62 yrs, ECOG PS 0/1) were enrolled from June to Nov 2009. Every pt received...