A randomized phase II study of gemcitabine (G) plus the cardiac glycoside huachansu (H) in the treatment of patients with locally advanced (LAPC) or metastatic pancreatic cancer (MPC).

4127 Background: Wild toad venom has been used for over 1,000 years as a traditional Chinese medicine; H, the extract of dried toad skin glands, is a potent cardiac glycoside without significant toxicity. H has demonstrated preliminary evidence of anti-tumor activity in phase I clinical trial evaluation (Cancer 2009, 115:5309-18). Methods: We conducted a randomized, single-blind, phase II clinical trial of G + H versus G + placebo in patients with LAPC or MPC. Plasma bufalin levels were performed in H-treated subjects. 80 evaluable subjects accrued from October 2007 to May 2010 and were treated with G 1,000mg/m2(iv on days 1, 8, 15, q 28d) plus either H (20 mL/m2 iv daily for 21 days followed by 7 days off, q 28d) or placebo. Demographic data is demonstrated in the table below. Results: Grade 3/4 adverse events, objective radiographic response rates (ORR), time to progression (TTP), quality of life (QOL), and overall survival (OS) were similar in the two groups (see table). There was not a statistically significant difference in the average plasma bufalin levels in patients with a radiographic partial response (PR) or stable disease versus those with progressive disease (PD) (0.098 ± 0.093 ng/mL vs. 0.071 ± 0.048 ng/mL, p=0.679). Conclusions: H when added to G was well tolerated but did not improve OS, TTP, QOL, or ORR. Further investigation of a more potent oral formulation of H is planned. H provided by Shenzhen 999 Traditional Chinese Medicine & Development Co., Ltd. Supported by NIH U19CA121503-01. Demographics and results. Huachansu plus gemcitabine Placebo plus gemcitabine Total Demographics Age, years (SD) 60.2 ± 9.5 61.7 ± 9.9 60.9 ± 9.6 Male/female (%) 23/16 (59, 41) 23/14 (62, 38) 46/30 (61,39) Karnfosky performance status (%) ± SD 84.9 ± 6.5 85.4 ± 5.0 85.1 ± 5.8 Stage (LAPC/MPC, %) 10/29 (26, 74) 8/29 (22, 78) 18, 58 (24, 76) Site (head/body/tail, %) 17, 9, 13 (44, 23, 33) 14, 8, 15 (38, 22, 40) 31, 17, 28 (41, 22, 37) Prior surgery (yes/no, %) 4, 35 (10, 90) 5, 32 (14, 86) 9, 70 (12, 92) Results ORR PR/stable disease/PD (%) 3, 18, 13 (9, 53, 38) 1, 21, 11 (3, 64, 33) 4, 40, 25 (6, 60, 34) TTP (days) 102 103 p = 0.626 OS (median days) 154 134 p = 0.831 Abbreviation: SD, standard deviation.