A phase I trial of weekly gemcitabine (GEM), administered as a constant dose-rate infusion, and docetaxel (DOC) in patients with advanced solid tumors (LOA-8)

Abstract

2090 Background: GEM and DOC have demonstrated single-agent antitumor activity against a variety of malignancies. Pharmacological studies of GEM have demonstrated that the intracellular concentration of its active triphosphate metabolite is maximized at a dose rate of approximately 10 mg/m2/minute. The major purposes of this study were to determine the maximally tolerated dose (MTD), dose-limiting toxicity (DLT), and toxicity profile for GEM and DOC when administered to patients with advanced solid tumors on a weekly schedule. Methods: Both GEM and DOC were administered on days 1 and 8 of each 21-day course, with GEM administered at a rate of 10 mg/m2/minute and DOC over 60 minutes (after GEM). The initial dose levels were 600 mg/m2 and 25 mg/m2 for GEM and DOC, respectively. Results: Eight patients (5 men, 3 women, median age 60 years old) with advanced solid tumors have been treated with 25+ courses at 2 dose levels. Three patients were treated at dose-level 1 without DLT. Five patients have now been treated at dose level 2 (GEM 800 mg/m2 and DOC 25 mg/m2), with 1 too early to evaluate. One patient developed DLT (grade IV neutropenia with fever) and 2 patients experienced grade III thrombocytopenia. No grade III-IV non-hematologic side effects have been observed. No major responses have been observed as of yet, but 3 patients had dissease stabilization for at least 4 courses of treatment. Conclusions: The MTD of GEM and DOC on the current weekly schedule has not been established as of yet. Patient accrual is on-going at dose-level 2. Six patients will be treated at this level before dose-escalation if no further DLT is observed. Updated results will be presented at the meeting. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Eli Lilly