Synergistic activity of PHY906 with capecitabine in pancreatic carcinoma.

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2007 ASCO Annual Meeting

Abstract No: 15116

Journal of Clinical Oncology, 2007 ASCO Annual Meeting Proceedings Part I. Vol 25, No. 18S (June 20 Supplement), 2007: 15116
M. W. Saif, S. Liu, A. Elfiky, Z. Jiang, Y. Cheng

Background:
Preclinical data indicates that PHY906, a traditional Chinese botanical
formulation, can reduce chemo-induced gastrointestinal toxicity while
simultaneously enhancing therapeutic efficacy of a broad-spectrum of
common anticancer agents.
Methods: Male NCR athymic nude mice
were transplanted with human PANC-1 cells. To determine the best dose
of combinational regimen, two dose ranges of capecitabine, 60 and 180
mg/kg bid for 14 consecutive days with two dose ranges of PHY906, 300
and 900 mg/kg bid on days 1-4 and days 8-11 were administered by gavage
in the first experiment. In the second experiment,
PHY906 was fixed at 500 mg/kg bid at days 1-4 and 8-11 while dose of
capecitabine was increased to 360 mg/kg bid for 14 consecutive days. A
dose of 180 mg/kg of capecitabine was also included for comparison with
previous experiments. In the third experiment, capecitabine at
360 mg/kg was selected to evaluate effect of different doses of PHY906
ranging from 100 mg/kg to 500 mg/kg on enhancement of antitumor
activity of capecitabine. PHY906 was always administered 30 minutes
prior to capecitabine. Tumor size, body weight and mortality were
monitored daily and mice were sacrificed when tumor size reached 10% of
body weight or on Day 21.
Results: PHY906 showed enhancement
of antitumor activity of capecitabine when both doses of PHY906 were
co-administered with both doses of capecitabine in first experiment. In second experiment,
increase of capecitabine dose from 180 mg/kg to 360 mg/kg significantly
increased disparity of tumor growth rates between capecitabine alone
and concomitant use of both PHY906 and capecitabine. Similar results
were obtained in third experiment using a dose of 360 mg/kg of
capecitabine and 500 mg/kg of PHY906 (p= 0.0018) as compared with
control, capecitabine or PHY906 alone. Similar observation was found in
mice bearing PAN-2 murine pancreatic cancer.
Conclusions: The
studies demonstrate that PHY906 potentiates antitumor activity of
capecitabine in human pancreatic carcinoma xenograft mouse model in all
capecitabine and PHY906 dosing regimens examined. Observed effect
appeared to be dependant on dosage of capecitabine. Therefore, we are
employing a dose intense weekly schedule for capecitabine with PHY906
in a phase I/II study in patients with advanced pancreatic cancer.