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
| Autor: | E. Gabriela Chiorean, Matthew Burns, Menggang Yu, David T. Hinkle, Jose A. Bufill, Romnee Clark, Higinia R. Cardenes, Nicki Coleman, Bruce W. Robb, Sonal P. Sanghani, Patrick J. Loehrer, Marissa A. Schiel, Colleen Curie, Julia K. Leblanc, Yan Tong |
|---|---|
| Rok vydání: | 2012 |
| Předmět: |
Adult
Diarrhea Male Oncology Cancer Research medicine.medical_specialty Colorectal cancer medicine.medical_treatment Irinotecan Toxicology Deoxycytidine Thymidylate synthase Disease-Free Survival Drug Administration Schedule Capecitabine Internal medicine Antineoplastic Combined Chemotherapy Protocols medicine Humans Pharmacology (medical) Thymidine phosphorylase Fatigue Neoadjuvant therapy Aged Neoplasm Staging Pharmacology Thymidine Phosphorylase biology Rectal Neoplasms Reverse Transcriptase Polymerase Chain Reaction business.industry Gene Expression Profiling Chemoradiotherapy Middle Aged medicine.disease Neoadjuvant Therapy Gene Expression Regulation Neoplastic Radiation therapy Treatment Outcome biology.protein Camptothecin Female Fluorouracil business medicine.drug |
| Zdroj: | Cancer Chemotherapy and Pharmacology. 70:25-32 |
| ISSN: | 1432-0843 0344-5704 |
| Popis: | 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.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.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.This neoadjuvant regimen was safe and demonstrated significant antitumor activity. High TP tumor gene expression was associated with obtaining pCR. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full text from SpringerLink