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

Abstract We have examined the application of 90 Y‐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 90 Y‐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 90 Y‐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 90 Y‐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 90 Y‐DOTA‐hLL2 ( p <0.001). These data suggest that addition of 90 Y‐DOTA‐cPAM4 RAIT to a gemcitabine treatment regimen may provide enhanced antitumor efficacy for the treatment of pancreatic cancer. © 2004 Wiley‐Liss, Inc.