title: 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.affiliation: Section of GI Cancers and Experimental Therapeutics, Tufts University School of Medicine, 800 Washington Street, Boston, MA, 02111, USA, wsaif@tuftsmedicalcenter.org.
authors.forename: Muhammad Wasif
authors.initials: MW
authors.lastname: Saif
authors.forename: Jia
authors.initials: J
authors.lastname: Li
authors.forename: Lynne
authors.initials: L
authors.lastname: Lamb
authors.forename: Kristin
authors.initials: K
authors.lastname: Kaley
authors.forename: Kyle
authors.initials: K
authors.lastname: Elligers
authors.forename: Zaoli
authors.initials: Z
authors.lastname: Jiang
authors.forename: Scott
authors.initials: S
authors.lastname: Bussom
authors.forename: Shwu-Huey
authors.initials: SH
authors.lastname: Liu
authors.forename: Yung-Chi
authors.initials: YC
authors.lastname: Cheng
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D000069287:Capecitabine; D003841:Deoxycytidine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D018572:Disease-Free Survival; D004365:Drugs, Chinese Herbal / Q000008:administration & dosage / Q000009:adverse effects; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D006801:Humans; D008297:Male; D008875:Middle Aged; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000473:pathology; D015996:Survival Rate; D016896:Treatment Outcome
chemical_list: D004365:Drugs, Chinese Herbal; C476037:PHY 906; D003841:Deoxycytidine; D000069287:Capecitabine; D005472:Fluorouracil