Phase II and gene expression analysis trial of neoadjuvant capecitabine plus irinotecan followed by capecitabine-based chemoradiotherapy for locally advanced rectal cancer: Hoosier Oncology Group GI03-53

E. Gabriela Chiorean, Sonal Sanghani, Marissa A. Schiel, Menggang Yu, Matthew Burns, Yan Tong, David T. Hinkle, Nicki Coleman, Bruce Robb, Julia Leblanc, Romnee Clark, Jose Bufill, Colleen Curie, Patrick J. Loehrer, Higinia Cardenes

Research output: Contribution to journalArticle

15 Scopus citations


Purpose: We designed this study in locally advanced rectal cancer to determine the pathological response, toxicity, and disease-free survival (DFS) with induction capecitabine plus irinotecan followed by capecitabine-based chemoradiotherapy (CRT) and analyze the gene expression of enzymes involved in the metabolism of capecitabine and irinotecan for associations with response and toxicity. Methods: Patients with T3/T4 or node positive rectal cancer were treated with capecitabine 1,000 mg/m 2 twice daily (BID) days 1-14, and irinotecan 200 mg/m 2 on day 1 every 21 days for 2 cycles, followed by capecitabine 825 mg/m 2 BID days 1-5 per week with concurrent radiotherapy 50.4 Gy in 28 fractions. Surgical resection occured a median of 7.4 weeks after CRT. Gene expression levels or sequencing were used to analyze carboxylesterase-converting enzymes (CES1, CES2), thymidylate synthase (TS), thymidine phosphorylase (TP), dehydropyrimidine dehydrogenase (DPD), topoisomerase I (TOPO I), and uridine-diphosphate (UDP) glucuronosyl transferase 1A1 in pre- and post-treatment tumor and normal tissue samples. Results: Twenty-two patients were enrolled, and 18 completed neoadjuvant therapy and underwent R0 resection. Two patients with UGT1A1 7/7 had grade 3 and 4 neutropenic fever and sepsis. Pathological complete response (pCR) occurred in 6 of 18 patients (33 %) and 10 (56 %) had tumor and/or nodal downstaging. The 3-year DFS was 75.5 % (95 % CI, 39.7-91.8 %). Locoregional control rate was 100 %. We observed higher TP gene expression in pCR patients, but no correlations with toxicity. Conclusions: This neoadjuvant regimen was safe and demonstrated significant antitumor activity. High TP tumor gene expression was associated with obtaining pCR.

Original languageEnglish (US)
Pages (from-to)25-32
Number of pages8
JournalCancer Chemotherapy and Pharmacology
Issue number1
StatePublished - Jul 1 2012



  • Capecitabine
  • Chemoradiotherapy
  • Gene expression
  • Irinotecan
  • Rectal cancer

ASJC Scopus subject areas

  • Cancer Research
  • Oncology
  • Pharmacology
  • Pharmacology (medical)
  • Toxicology

Cite this