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Cancer Chemotherapy and Pharmacology

, Volume 73, Issue 2, pp 373–380 | Cite as

First-in-human phase II trial of the botanical formulation PHY906 with capecitabine as second-line therapy in patients with advanced pancreatic cancer

  • Muhammad Wasif Saif
  • Jia Li
  • Lynne Lamb
  • Kristin Kaley
  • Kyle Elligers
  • Zaoli Jiang
  • Scott Bussom
  • Shwu-Huey Liu
  • Yung-Chi Cheng
Original Article

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.

Keywords

Capecitabine PHY906 Herbal medicines Pancreatic cancer Diarrhea Hand-foot syndrome (HFS) 

Notes

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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Copyright information

© Springer-Verlag Berlin Heidelberg 2013

Authors and Affiliations

  • Muhammad Wasif Saif
    • 1
  • Jia Li
    • 2
  • Lynne Lamb
    • 3
  • Kristin Kaley
    • 3
  • Kyle Elligers
    • 3
  • Zaoli Jiang
    • 3
  • Scott Bussom
    • 3
  • Shwu-Huey Liu
    • 4
  • Yung-Chi Cheng
    • 3
  1. 1.Section of GI Cancers and Experimental TherapeuticsTufts University School of MedicineBostonUSA
  2. 2.VA Connecticut Healthcare SystemWest HavenUSA
  3. 3.Yale University School of MedicineNew HavenUSA
  4. 4.Phytoceutica Inc.New HavenUSA

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