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Combined 90Yttrium‐DOTA‐labeled PAM4 antibody radioimmunotherapy and gemcitabine radiosensitization for the treatment of a human pancreatic cancer xenograft

We have examined the application of 90Y‐DOTA‐cPAM4, anti‐MUC1 IgG, in combination with the front‐line drug gemcitabine as a potential therapeutic for pancreatic cancer. Athymic nude mice bearing CaPan1 human pancreatic cancer xenografts were administered 2 mg of gemcitabine on days 0, 3, 6, 9 and 12 with concurrent 90Y‐DOTA‐cPAM4 (100 μCi) provided on day 0. A second group of mice received a second cycle of treatment 5 weeks after the start of the first cycle. Control groups of mice included those that received either treatment arm alone, the combined modality treatment employing a nontargeting control antibody (hLL2, anti‐B‐cell lymphoma) and a final group that was left untreated. Gemcitabine administered as a single agent provided no antitumor effect. A single cycle of the combined 90Y‐DOTA‐cPAM4 and gemcitabine treatment provided greater inhibition of tumor growth than was observed for any of the other treatment procedures. Tumor growth was delayed for a period of 7 weeks. Two cycles of gemcitabine with concomitant 90Y‐DOTA‐cPAM4 yielded significant tumor regression and increased median survival to 21 weeks vs. 12 weeks for mice receiving a single cycle of therapy (p<0.024). Median tumor volume doubling‐times were 18 weeks in mice treated with 2‐cycles of therapy vs. 7 weeks in mice given only 1‐cycle (p<0.001), and 3.5 weeks for the group that received 2‐cycles of gemcitabine concomitant with equitoxic nontargeting 90Y‐DOTA‐hLL2 (p<0.001). These data suggest that addition of 90Y‐DOTA‐cPAM4 RAIT to a gemcitabine treatment regimen may provide enhanced antitumor efficacy for the treatment of pancreatic cancer. © 2004 Wiley‐Liss, Inc.