title: Phase I dose escalation study of capecitabine and erlotinib concurrent with radiation in locally advanced pancreatic cancer.
abstract: OBJECTIVE
  Pancreatic cancer is one of the leading causes of cancer-related deaths worldwide. The median survival of locally advanced nonoperable disease is approximately 9 months. 5-FU-based chemoradiotherapy has been the standard treatment. However, the survival benefit of this approach is modest. To improve the efficacy of 5-FU-based chemoradiation therapy, we evaluated the safety and feasibility of the combination of capecitabine and erlotinib with radiotherapy in this group of patients.
  
  
  METHODS
  A traditional "3 + 3" dose escalation design was adopted in the study. A total of four dose levels were designed. For safety purpose, a minus I dose level (-I) was also planned. The -I level consisted of capecitabine 600 mg/m² and erlotinib 50 mg daily, and the remaining four dose levels were as follows: level I: capecitabine 600 mg/m² bid (twice daily); level II: 700 mg/m² bid; level III: 825 mg/m² bid; and level IV: 925 mg/m² bid. Erlotinib was administered at 100 mg daily at all dose levels. Erlotinib and capceitabine were given continuously Monday through Friday concurrent with radiotherapy (50.4 Gy in 28 fractions).
  
  
  RESULTS
  A total of 18 patients were consented. Fifteen patients were enrolled and completed therapy. No dose-limiting toxicity was observed. The most frequent side effects were lymphopenia, nausea, vomiting, diarrhea, electrolyte imbalances, and skin rashes. The majority of the toxicities were grade 1 and 2. No objective response was observed. The median progression-free survival was 0.59 years (95 % CI 0.31-1.1), and the median overall survival was 1.1 years (95 % CI 0.62-1.59).
  
  
  CONCLUSIONS
  The combination of capecitabine and erlotinib with radiotherapy in locally advanced pancreatic cancer is well tolerated and feasible at the dose level of capecitabine 925 mg/m² bid and erlotinib 100 mg daily.
authors.affiliation: Marlene and Stewart Greenebaum Cancer Center, University of Maryland School of Medicine, Baltimore, MD, 21201, USA, yjiang@umm.edu.
authors.forename: Yixing
authors.initials: Y
authors.lastname: Jiang
authors.forename: Heath B
authors.initials: HB
authors.lastname: Mackley
authors.forename: Eric T
authors.initials: ET
authors.lastname: Kimchi
authors.forename: Junjia
authors.initials: J
authors.lastname: Zhu
authors.forename: Niraj
authors.initials: N
authors.lastname: Gusani
authors.forename: Jussuf
authors.initials: J
authors.lastname: Kaifi
authors.forename: Kevin F
authors.initials: KF
authors.lastname: Staveley-O'Carroll
authors.forename: Chandra P
authors.initials: CP
authors.lastname: Belani
mesh_terms: D000230:Adenocarcinoma / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D000069287:Capecitabine; D059248:Chemoradiotherapy / Q000009:adverse effects; D015331:Cohort Studies; D003841:Deoxycytidine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D000069347:Erlotinib Hydrochloride; D005240:Feasibility Studies; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D005500:Follow-Up Studies; D006801:Humans; D008231:Lymphopenia / Q000139:chemically induced / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D010179:Pancreas / Q000000981:diagnostic imaging / Q000187:drug effects* / Q000473:pathology / Q000528:radiation effects; D010190:Pancreatic Neoplasms / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy; D011799:Quinazolines / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D011859:Radiography; D012720:Severity of Illness Index; D016019:Survival Analysis; D047368:Tumor Burden / Q000187:drug effects / Q000528:radiation effects
chemical_list: D011799:Quinazolines; D003841:Deoxycytidine; D000069287:Capecitabine; D000069347:Erlotinib Hydrochloride; D005472:Fluorouracil