Abstract

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

Category: Gastrointestinal (Noncolorectal) Cancer

Meeting: 2009 ASCO Annual Meeting

Citation: J Clin Oncol 27:7s, 2009 (suppl; abstr 4620)

Abstract No: 4620

Author(s): K. Pennington, M. J. Guarino, A. N. Serafini, C. Rocha-Lima, K. Suppiah, C. J. Schneider, D. V. Gold, R. M. Sharkey, W. A. Wegener, D. M. Goldenberg; Goshen Center for Cancer Care, Goshen, IN; Helen F. Graham Cancer Center, Newark, DE; University of Miami School of Medicine, Miami, FL; Garden State Cancer Center, Belleville, NJ; Immunomedics, Inc., Morris Plains, NJ

Abstract:

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 metastatic disease) have now been treated at the first 2 dose levels (6.5 and 9.0 mCi/m2 90Y-hPAM4 x 3) with hematologic toxicity all transient Grade 1-2 (NCI CTC v3). 111In-hPAM4 imaging showed normal biodistribution, evidence of tumor targeting and acceptable dosimetry estimates to normal organs per treatment cycle. Two pts had tumor responses to initial treatment with significant decreases in FDG metabolic activity on PET imaging, regression of lesion sizes on CT, and CA19.9 decreases. Both pts continue in excellent performance status now at 9 and 11 months after study entry, after receiving a total of 3 and 4 treatment cycles, respectively, without additional toxicity. A 3rd pt with a stable response by PET and CT 4 weeks after initial treatment and decreases in CA19.9 levels is now undergoing a 2nd treatment cycle. Four other pts had early progression of disease by or before post-treatment week-4 evaluation, and the remaining pt is still being evaluated.
Conclusions: Dose escalation is continuing after fractionated radioimmunotherapy with 90Y-hPAM4 plus low-dose gemcitabine demonstrated therapeutic activity at the first two 90Y dose levels, with minimal hematologic toxicity, even after 4 treatment cycles.