title: A phase I study of sorafenib, oxaliplatin and 2 days of high dose capecitabine in advanced pancreatic and biliary tract cancer: a Wisconsin oncology network study.
abstract: Chemotherapy has yielded minimal clinical benefit in pancreatic and biliary tract cancer. A high-dose, short course capecitabine schedule with oxaliplatin, has shown some efficacy with a lower incidence of palmar-plantar erythrodysesthesia. Achieving high exposures of the targeted agent sorafenib may be possible with this shorter schedule of capecitabine by avoiding dermatologic toxicity. All patients had pancreatic or biliary tract cancer. Patients in both cohorts received oxaliplatin 85 mg/m2 followed by capecitabine 2,250 mg/m2 PO every 8 h x 6 doses starting on days 1 and 15 of a 28 day cycle, or 2DOC (2 Day Oxaliplatin/Capecitabine). Cohort 1 used sorafenib 200 mg BID, and cohort 2 used sorafenib 400 mg BID. Sixteen patients were enrolled. Across all cycles the most common grade 1 or 2 adverse events were fatigue (10 pts), diarrhea (10 pts), nausea (9 pts), vomiting (8 pts), sensory neuropathy (8 pts), thrombocytopenia (7 pts), neutropenia (5 pts), and hand-foot syndrome (5 pts). Grade 3 toxicites included neutropenia, mucositis, fatigue, vomiting and diarrhea. Cohort 1 represented the MTD. Two partial responses were seen, one each in pancreatic and biliary tract cancers. The recommended phase II dose of sorafenib in combination with 2DOC is 200 mg BID. There were infrequent grade 3 toxicities, most evident with sorafenib at 400 mg BID.
authors.affiliation: University of Wisconsin Carbone Cancer Center and the University of Wisconsin School of Medicine and Public Health, 600 Highland Avenue, K6/548 CSC, Madison, WI 53792, USA. Ns3@medicine.wisc.edu
authors.forename: Noelle K
authors.initials: NK
authors.lastname: LoConte
authors.forename: Kyle D
authors.initials: KD
authors.lastname: Holen
authors.forename: William R
authors.initials: WR
authors.lastname: Schelman
authors.forename: Daniel L
authors.initials: DL
authors.lastname: Mulkerin
authors.forename: Dustin A
authors.initials: DA
authors.lastname: Deming
authors.forename: Hilary R
authors.initials: HR
authors.lastname: Hernan
authors.forename: Anne M
authors.initials: AM
authors.lastname: Traynor
authors.forename: Timothy
authors.initials: T
authors.lastname: Goggins
authors.forename: David
authors.initials: D
authors.lastname: Groteluschen
authors.forename: Kurt
authors.initials: K
authors.lastname: Oettel
authors.forename: Emily
authors.initials: E
authors.lastname: Robinson
authors.forename: Sam J
authors.initials: SJ
authors.lastname: Lubner
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D001661:Biliary Tract Neoplasms / Q000188:drug therapy* / Q000473:pathology; D000069287:Capecitabine; D003710:Demography; D003841:Deoxycytidine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D005260:Female; D005472:Fluorouracil / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D006801:Humans; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D009536:Niacinamide / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D009944:Organoplatinum Compounds / Q000009:adverse effects / Q000627:therapeutic use*; D000077150:Oxaliplatin; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000473:pathology; D010671:Phenylurea Compounds / Q000009:adverse effects / Q000627:therapeutic use*; D000077157:Sorafenib; D016896:Treatment Outcome; D014922:Wisconsin
chemical_list: D000970:Antineoplastic Agents; D009944:Organoplatinum Compounds; D010671:Phenylurea Compounds; D000077150:Oxaliplatin; D003841:Deoxycytidine; D009536:Niacinamide; D000069287:Capecitabine; D000077157:Sorafenib; D005472:Fluorouracil