First-in-human phase II trial of the botanical formulation PHY906 with capecitabine as second-line therapy in patients with advanced pancreatic cancer
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Preclinical studies showed a Chinese botanical formula, PHY906, has synergistic anti-tumor activity with capecitabine. Our phase I study determined maximal tolerated dose of capecitabine 1,500 mg/m2 BID day 1–7 and PHY906 800 mg BID day 1–4 every 2 weeks. We conducted this phase II study to explore the efficacy of capecitabine and PHY906 in patients with advanced pancreatic cancer who were previously treated with gemcitabine-based regimens.
Patients with pancreatic cancer and an Eastern Cooperative Oncology Group performance status of 0–2 received PHY906 and capecitabine. Toxicity was assessed per NCI-CTCAE v3.0 and response per response evaluation criteria in solid tumors q 6 weeks. Correlative studies of cytokines, chemokines and growth factors were tested using a cytometric bead array. Quality of life was assessed by utilizing Edmonton symptom assessment system. The primary objective was overall survival.
The study enrolled 25 patients. Median progression-free survival (mPFS) was 10.1 weeks (range 0.4–54.1) and median overall survival (mOS) was 21.6 weeks (range 0.4–84.1). Eighteen patients received at least 2 cycles, and achieved mPFS of 12.3 weeks and mOS of 28 weeks. Six-month survival rate was 44 % (11/25). Unsupervised clustering of patients grouped those with shortened survival together by their cytokine profile showed that only IL-6 had a significant difference (p < .001) between short- and long-term survivors.
Capecitabine plus PHY906 provides a safe and feasible salvage therapy after gemcitabine failure for APC. Role of IL-6 in tumor progression and tumor cachexia needs to be investigated with respect to its relation to pathophysiology of pancreatic cancer and development of anti-IL-6 therapeutics.
KeywordsCapecitabine PHY906 Herbal medicines Pancreatic cancer Diarrhea Hand-foot syndrome (HFS)
This study was approved and funded by the National Comprehensive Cancer Network (NCCN) from general research support provided by Roche Laboratories; PO1CA154295; and Dr. Cheng is a Fellow of the National Foundation for Cancer Research.
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