Multicenter study of radiosensitizing gemcitabine combined with fractionated radioimmunotherapy for repeated treatment cycles in advanced pancreatic cancer

4620 Background: In a phase I study, a single dose of 90Y-labeled anti-mucin humanized antibody, hPAM4 (90Y-hPAM4), led to several transient reductions or stabilization of lesions in advanced pancreatic cancer, with bone marrow toxicity limiting the maximum tolerated dose to 20 mCi/m2. Preclinical studies showed gemcitabine enhanced radioimmunotherapy, so a phase Ib study was undertaken to evaluate repeated treatment cycles of 90Y-hPAM4 plus gemcitabine. Methods: Patients (pts) with previously untreated, locally advanced or metastatic, pancreatic cancer were treated in 4-week cycles (200 mg/m2 gemcitabine once-weekly; 111In-hPAM4 the 1st wk for imaging, biodistribution, and dosimetry; 90Y-hPAM4 once-weekly the last 3 wks), which could be repeated in the absence of progression or unacceptable toxicity. The 90Y-dose was escalated by patient cohort following a 3+3 design, with tumor responses assessed by CT and FDG/PET imaging, and by CA19.9 serum levels. Results: Eight pts (3F/5M, 56–72 years old, 7 with me...