A phase II study of capecitabine (CAP) plus PHY906 in patients (pts) with advanced pancreatic cancer (APC)

Abstract

e15508 Background: Gemcitabine (G) is regarded as the standard treatment for pts with APC. However, a standard second-line chemotherapy regimen has yet to be defined after G. PHY906, a 4-herb traditional Chinese medicine has a history of > 1,800 yrs of human use to treat GI symptoms including diarrhea. Preclinical studies showed that PHY906 may potentiate antitumor activity of CAP in human PANC-1 xenograft (ASCO 2007). A phase I study showed that CAP can be escalated up to 1750 mg/m2 PO BID on d1- 7 and PHY906 800mg PO BID on d1–4 q 2 wks with no DLTs (ASCO, 2008). Delivered dose-intensity of CAP was similar at 1750mg/m2 dose level as 1500mg/m2. Therefore, 1500mg/m2 of CAP and PHY906 was further tested in a phase II study as second-line treatment in pts with APC. Methods: Pts with G-refractory APC with ECOG PS <2 were treated with CAP 1500mg/m2 d1–7 with PHY906 800mg d1–4 q 2 wks. Response was assessed by CT scan according to RECIST q 6 wks and toxicity according to NCI-CTC v3.0. Primary objective is overall survival. Secondary objectives include overall RR, PFS and measurement of cytokines to assess inhibition of NF-kappa B, a possible mechanism responsible for PHY906's pharmacological activity. Results: As of January 5, 2009, 25 pts have been enrolled. Baseline characteristics include median age, 65 (range, 40–85); male/female,15/10; ECOG PS 0/1, 4/19; median cycles: 3 (r: 0.5–15). At this point 5 pts are still in active treatment. 4 pts have confirmed OS > 6 ms (1 still on study) with 2 further pts approaching 6 ms. Among evaluable pts, 1 had PR (5.3%), 11 SD (57.9%) and 7 PD (36.8%) after initial restaging scan. 36 % pts had >30% reduction in CA19–9 as biochemical response. There were 7 deaths on/within 30 days of study treatment, 6 related to PD and 1 had acute MI. G3/4 toxicities diarrhea 3/25 (12%), fatigue, 1/25 (4%), HFS 1/25 (4%) and mucositis 1/25 (4%). 1 pt was removed from study due to G3 HFS. Biomarker studies (IL4, GM-CSF, TNF-alpha, IL10, MCP-1, IL2, IL6) are ongoing. Conclusions: This is the first clinical study to evaluate a botanical formulation PHY906 with CAP in G-refractory APC pts. CAP + PHY906 regimen appears a safe and feasible salvage therapy in APC and warrants further investigation. In addition, PHY906 may have a cytoprotective antidiarrheal and anti-HFS effect, making treatment with CAP more tolerable. [Table: see text]