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

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/m(2) 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.

• Authors: Muhammad Wasif Saif, Jia Li, Lynne Lamb, Kristin Kaley, Kyle Elligers, Zaoli Jiang, Scott Bussom, Shwu-Huey Liu, Yung-Chi Cheng
• Journal: Cancer chemotherapy and pharmacology (Cancer Chemother Pharmacol) Vol. 73 Issue 2 Pg. 373-80 (Feb 2014) ISSN: 1432-0843 [Electronic] Germany
• PMID: 24297682 (Publication Type: Clinical Trial, Phase II, Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Drugs, Chinese Herbal
• PHY 906
• Deoxycytidine
• Capecitabine
• Fluorouracil

Topics

• Aged
• Aged, 80 and over
• Antineoplastic Combined Chemotherapy Protocols (adverse effects, therapeutic use)
• Capecitabine
• Deoxycytidine (administration & dosage, adverse effects, analogs & derivatives)
• Disease-Free Survival
• Drugs, Chinese Herbal (administration & dosage, adverse effects)
• Female
• Fluorouracil (administration & dosage, adverse effects, analogs & derivatives)
• Humans
• Male
• Middle Aged
• Pancreatic Neoplasms (drug therapy, pathology)
• Survival Rate
• Treatment Outcome