Title : 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 - Chiorean_2012_Cancer.Chemother.Pharmacol_70_25 |
Author(s) : Chiorean EG , Sanghani S , Schiel MA , Yu M , Burns M , Tong Y , Hinkle DT , Coleman N , Robb B , LeBlanc J , Clark R , Bufill J , Curie C , Loehrer PJ , Cardenes H |
Ref : Cancer Chemother Pharmacol , 70 :25 , 2012 |
Abstract :
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 occurred 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. |
PubMedSearch : Chiorean_2012_Cancer.Chemother.Pharmacol_70_25 |
PubMedID: 22610353 |
Substrate | Capecitabine |
Chiorean EG, Sanghani S, Schiel MA, Yu M, Burns M, Tong Y, Hinkle DT, Coleman N, Robb B, LeBlanc J, Clark R, Bufill J, Curie C, Loehrer PJ, Cardenes H (2012)
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
Cancer Chemother Pharmacol
70 :25
Chiorean EG, Sanghani S, Schiel MA, Yu M, Burns M, Tong Y, Hinkle DT, Coleman N, Robb B, LeBlanc J, Clark R, Bufill J, Curie C, Loehrer PJ, Cardenes H (2012)
Cancer Chemother Pharmacol
70 :25