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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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Abstract

Background

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.

Methods

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.

Results

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.

Conclusions

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.

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Acknowledgments

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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Authors and Affiliations

  1. Section of GI Cancers and Experimental Therapeutics, Tufts University School of Medicine, 800 Washington Street, Boston, MA, 02111, USA

    Muhammad Wasif Saif

  2. VA Connecticut Healthcare System, West Haven, CT, USA

    Jia Li

  3. Yale University School of Medicine, New Haven, CT, USA

    Lynne Lamb, Kristin Kaley, Kyle Elligers, Zaoli Jiang, Scott Bussom & Yung-Chi Cheng

  4. Phytoceutica Inc., New Haven, CT, USA

    Shwu-Huey Liu

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  1. Muhammad Wasif Saif
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Correspondence to Muhammad Wasif Saif.

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Saif, M.W., Li, J., Lamb, L. et al. First-in-human phase II trial of the botanical formulation PHY906 with capecitabine as second-line therapy in patients with advanced pancreatic cancer. Cancer Chemother Pharmacol 73, 373–380 (2014). https://doi.org/10.1007/s00280-013-2359-7

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