Abstract
679 Background: Gemcitabine and irinotecan, have both demonstrated efficacy in patients with MBC. The incorporation of gemcitabine into DNA enhances cleavage complexes induced by a topo I inhibitor in vitro. Objectives: response, tolerability, and translational studies measuring topo I and PK. Methods: Inclusion criteria: male and female patients with MBC, prior anthracycline therapy, ECOG PS of ≤ 2, adequate organ function ≤ 3 prior chemotherapy regimens for MBC. 26 patients received gemcitabine at 1000 mg/m2 and irinotecan at 100 mg/m2 on days 1 and 8 of a 21 day cycle. Response evaluated by RECIST criteria. Topo I: Tumors were biopsied by fine needle aspiration (FNA) prior to initiation of therapy. Topo I was detected using immunofluorscence with a murine monclonal antibody against the protein’s C-terminus. PK: Irinotecan: A previously validated limited sampling strategy was used. Gemcitabine: Blood was collected over 24 hrs following the first dose. Intracellular nucleotides were also quantified in PBMCs using established techniques. Results: Of the 26 patients enrolled, 26 have been evaluated for response with an overall response rate of 31% (CR=0, PR=8 (1 unconfirmed), SD=4, PD=14). No febrile neutropenia was seen. Grade 3 non-hematologic toxicities included fatigue (1), N/V (3), dehydration (1) and diarrhea (1). Results from the 6 tumors assessed for topo I are listed in the table below. PK data will be available at presentation. Conclusion: Preliminary results indicate that GI is an active combination for metastatic breast cancer with acceptable toxicity; therefore accrual continues. Additionally, topo I levels and localization can be measured in breast tumors using FNA. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration AstraZeneca, Lilly Oncology Lilly Oncology, Pfizer GlaxoSmithKline, Lilly Oncology, Pfizer AstraZeneca, Lilly Oncology
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