title: Phase Ib Study of PEGylated Recombinant Human Hyaluronidase and Gemcitabine in Patients with Advanced Pancreatic Cancer.
abstract: This phase Ib study evaluated the safety and tolerability of PEGylated human recombinant hyaluronidase (PEGPH20) in combination with gemcitabine (Gem), and established a phase II dose for patients with untreated stage IV metastatic pancreatic ductal adenocarcinoma (PDA). Objective response rate and treatment efficacy using biomarker and imaging measurements were also evaluated.
  
  
  
  Patients received escalating intravenous doses of PEGPH20 in combination with Gem using a standard 3+3 dose-escalation design. In cycle 1 (8 weeks), PEGPH20 was administrated twice weekly for 4 weeks, then once weekly for 3 weeks; Gem was administrated once weekly for 7 weeks, followed by 1 week off treatment. In each subsequent 4-week cycle, PEGPH20 and Gem were administered once weekly for 3 weeks, followed by 1 week off. Dexamethasone (8 mg) was given pre- and post-PEGPH20 administration. Several safety parameters were evaluated.
  
  
  
  Twenty-eight patients were enrolled and received PEGPH20 at 1.0 (n = 4), 1.6 (n = 4), or 3.0 μg/kg (n = 20), respectively. The most common PEGPH20-related adverse events were musculoskeletal and extremity pain, peripheral edema, and fatigue. The incidence of thromboembolic events was 29%. Median progression-free survival (PFS) and overall survival (OS) rates were 5.0 and 6.6 months, respectively. In 17 patients evaluated for pretreatment tissue hyaluronan (HA) levels, median PFS and OS rates were 7.2 and 13.0 months for "high"-HA patients (n = 6), and 3.5 and 5.7 months for "low"-HA patients (n = 11), respectively.
  
  
  
  PEGPH20 in combination with Gem was well tolerated and may have therapeutic benefit in patients with advanced PDA, especially in those with high HA tumors. Clin Cancer Res; 22(12); 2848-54. ©2016 AACR.
authors.affiliation: Fred Hutchinson Cancer Research Center, Seattle, Washington. University of Washington School of Medicine, Seattle, Washington. srh@fhcrc.org.
authors.forename: Sunil R
authors.initials: SR
authors.lastname: Hingorani
authors.affiliation: Fred Hutchinson Cancer Research Center, Seattle, Washington. University of Washington School of Medicine, Seattle, Washington.
authors.forename: William P
authors.initials: WP
authors.lastname: Harris
authors.affiliation: Highlands Oncology Group, Fayetteville, Arkansas.
authors.forename: J Thaddeus
authors.initials: JT
authors.lastname: Beck
authors.affiliation: Medical Radiological Research Center, Obninsk, Russian Federation.
authors.forename: Boris A
authors.initials: BA
authors.lastname: Berdov
authors.affiliation: Indiana University Melvin and Bren Simon Cancer Center, Indianapolis, Indiana.
authors.forename: Stephanie A
authors.initials: SA
authors.lastname: Wagner
authors.affiliation: Omsk Regional Budget Medical Institution: Clinical Oncological Center, Omsk, Russian Federation.
authors.forename: Eduard M
authors.initials: EM
authors.lastname: Pshevlotsky
authors.affiliation: Russian Oncology Research Center n.a. N.N. Blokhin, Moscow, Russian Federation.
authors.forename: Sergei A
authors.initials: SA
authors.lastname: Tjulandin
authors.affiliation: Chelyabinsk Regional Clinical Oncology Center, Chelyabinsk, Russian Federation.
authors.forename: Oleg A
authors.initials: OA
authors.lastname: Gladkov
authors.affiliation: Icahn School of Medicine at Mt. Sinai, New York, New York.
authors.forename: Randall F
authors.initials: RF
authors.lastname: Holcombe
authors.affiliation: Imaging Endpoints, Scottsdale, Arizona.
authors.forename: Ronald
authors.initials: R
authors.lastname: Korn
authors.affiliation: Moffitt Cancer Center, Tampa, Florida.
authors.forename: Natarajan
authors.initials: N
authors.lastname: Raghunand
authors.affiliation: Halozyme Therapeutics, San Diego, California.
authors.forename: Samuel
authors.initials: S
authors.lastname: Dychter
authors.affiliation: Halozyme Therapeutics, San Diego, California.
authors.forename: Ping
authors.initials: P
authors.lastname: Jiang
authors.affiliation: Halozyme Therapeutics, San Diego, California.
authors.forename: H Michael
authors.initials: HM
authors.lastname: Shepard
authors.affiliation: Hofstra North Shore-LIJ School of Medicine, Hempstead, New York.
authors.forename: Craig E
authors.initials: CE
authors.lastname: Devoe
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D021441:Carcinoma, Pancreatic Ductal / Q000188:drug therapy* / Q000473:pathology; D003841:Deoxycytidine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D003907:Dexamethasone / Q000627:therapeutic use; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D006821:Hyaluronoglucosaminidase / Q000009:adverse effects / Q000737:chemistry / Q000235:genetics / Q000627:therapeutic use*; D008113:Liver Neoplasms / Q000556:secondary; D008175:Lung Neoplasms / Q000556:secondary; D008207:Lymphatic Metastasis / Q000473:pathology; D008297:Male; D008875:Middle Aged; D010179:Pancreas / Q000473:pathology; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000473:pathology; D011092:Polyethylene Glycols / Q000737:chemistry; D011994:Recombinant Proteins / Q000235:genetics / Q000627:therapeutic use; D012426:Russia; D016896:Treatment Outcome; D014481:United States; D000093542:Gemcitabine
chemical_list: D011994:Recombinant Proteins; D003841:Deoxycytidine; D011092:Polyethylene Glycols; D003907:Dexamethasone; D006821:Hyaluronoglucosaminidase; D000093542:Gemcitabine
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