Phase I trial of 17-dimethylaminoethylamino-17-demethoxygeldanamycin (17-DMAG) administered twice weekly

3566 Background: 17-DMAG binds to heat-shock protein 90, leading to degradation of oncogene client proteins, inhibiting tumor growth. Preclinically, 17-DMAG has potent antitumor activity. Methods: 17-DMAG was given by 1–2 hour infusion twice weekly for 4 weeks/28-day cycle. Starting dose: 1mg/m2/dose. Eligibility: ECOG = 2, adequate organ function. Exclusions: prolonged QTc/uncontrolled illness. An accelerated titration escalation design was used; one patient (pt)/dose level was entered until a single pt experienced dose-limiting toxicity (DLT) or 2 pts have grade (gr) = 2 toxicity during the first cycle. Ending the accelerated phase, it converts to a standard 3–6 pt/cohort design. Objectives: To determine the toxicity profile, pharmacokinetics (PK), pharmacodynamics (PD) and MTD of twice weekly 17-DMAG. Plasma samples collected before and up to 48 hours after 17-DMAG infusion were analyzed by LC-MS. Results: 23 pts were accrued and treated; Diagnosis: renal cell-1, pancreatic-2, medullary thyroid-1, NSCL...