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UGT1A1 Polymorphisms and Mutations Affect Anticancer Drug Therapy
Published in Sherry X. Yang, Janet E. Dancey, Handbook of Therapeutic Biomarkers in Cancer, 2021
Tristan M. Sissung, Roberto Barbier, Lisa M. Cordes, William D. Figg
Irinotecan is included in a class of topoisomerase I inhibitors that is indicated for the treatment of metastatic colorectal cancer and metastatic pancreatic cancer (https://www.accessdata.fda.gov/drugsatfda_docs/label/2015/207793lbl.pdf). Irinotecan (CPT-11) is a semisynthetic, water-soluble derivative of camptothecin, an alkaloid which was isolated from the bark and wood of the Chinese tree Camptotheca acuminata. Irinotecan has a more-favorable toxicity profile than that of camptothecin [76] and has activity in colorectal and pancreatic cancer, particularly in combination with fluorouracil and leucovorin (i.e. FOLFIRI) with or without oxaliplatin (i.e. FOLFIRINOX, FOLFOXIRI) [77–81]. For most patients who are able to receive intensive therapy, four first-line options serve as the treatment backbone for metastatic colon cancer: FOLFOX (fluorouracil, leucovorin, and oxaliplatin), FOLFIRI, CapeOx (capecitabine and oxaliplatin), or FOLFOXIRI (see NCCN Colon Cancer Version 3.2020). One regimen is not considered preferable, and thus treatment decisions are based on patient-specific factors and toxicity profiles of the individual therapies.
Colorectal Cancer
Published in Pat Price, Karol Sikora, Treatment of Cancer, 2020
After over 40 years of frustratingly slow progress with conventional cytotoxics, the last 15 years have been remarkable due to the realization of new active agents of different biological mechanisms of action with specific molecular targets, which have incrementally improved response rates and overall survival over and above 5-FU and best supportive care (BSC) alone. The chemotherapeutic agents irinotecan and oxaliplatin now form part of the doublet chemotherapy approach (with 5-FU/LV) in the majority of patients worldwide, in the form of FOLFOX (or CAPOX) or FOLFIRI. There has also been a recent resurgence of using three cytotoxic agents combined: FOLFOX plus irinotecan (FOLFOXIRI regimen; see later).
Treatment of Metastatic Disease
Published in Peter Sagar, Andrew G. Hill, Charles H. Knowles, Stefan Post, Willem A. Bemelman, Patricia L. Roberts, Susan Galandiuk, John R.T. Monson, Michael R.B. Keighley, Norman S. Williams, Keighley & Williams’ Surgery of the Anus, Rectum and Colon, 2019
Jürgen Weitz, Carina Riediger, Annika Stange, Ralf-Thorsten Hoffmann, David Morris
Recently, evidence for the synergistic activity of 5-FU, oxaliplatin and irinotecan led to the development of the triplet chemotherapy regimen oxaliplatin, irinotecan and fluorouracil (FOLFOXIRI), which was superior to FOLFIRI in a phase III randomised trial (GONO; see Table 40.3).19
Effect of Glutamine on Short-term Surgical Outcomes in Rectal Cancer Patients Receiving Neoadjuvant Therapy: A Propensity Score Matching Study
Published in Nutrition and Cancer, 2023
Gang Tang, Feng Pi, Zhengqiang Wei, Xiangshu Li
The neoadjuvant regimen was chemotherapy alone, short-course radiotherapy, or chemoradiation. Chemotherapy alone generally included the administration of fluorouracil in combination with oxaliplatin (FOLFOX), capecitabine in combination with oxaliplatin (XELOX), or fluorouracil, oxaliplatin, and irinotecan (FOLFOXIRI) for 2–8 cycles prior to surgery. The waiting period was 1–2 weeks for chemotherapy. Short-course radiotherapy (5 × 5 Gy) is usually followed by surgery within 10 day. Five weeks of chemoradiation (25 × 2 Gy) with concurrent oral capecitabine (825 mg/m2 twice a day) was followed by surgery after approximately 6–8 weeks (with or without 1–3 cycles of XELOX). After the completion of neoadjuvant therapy, the decision to proceed to surgery was based on the clinical, endoscopic, and imaging evaluation results and the patient’s clinical response to treatment. The timing of the procedure was determined by the surgical team.
A prognostic nomogram for intrahepatic progression-free survival in patients with colorectal liver metastases after ultrasound-guided percutaneous microwave ablation
Published in International Journal of Hyperthermia, 2022
Si Qin, Huabin Hu, Rui Cui, Jing Lin, Yiming Liu, Yimin Wang, Yao Chen, Guangjian Liu
Patients with advanced CRC, CRLMs larger than 3 cm, and >5 CRLMs received chemotherapy before MWA to reduce tumor burden. The chemotherapy regimen was oxaliplatin-based (n = 98), including XELOX and mFOLFOX6; a FOLFIRI regimen (n = 22); and FOLFOXIRI (n = 30). Bevacizumab (n = 15) and cetuximab (n = 8) were additionally administered to 23 patients. The number of chemotherapy cycles ranged from 2 to 12. The response to pre-operative chemotherapy was evaluated by CECT/MRI after every four cycles of treatment according to the Response Evaluation Criteria in Solid Tumors (RECIST) [26]. During chemotherapy, the need for ablation was reconsidered at a multidisciplinary meeting each time a response to chemotherapy was observed. The interval between chemotherapy and MWA was 1–14 days. Patients with a high clinical risk score for tumor recurrence (score >2) received chemotherapy after MWA to reduce recurrence. Eleven patients did not undergo chemotherapy after MWA because they were unwilling or their physical status was unsuitable for chemotherapy administration.
New avenues in pancreatic cancer: exploiting microRNAs as predictive biomarkers and new approaches to target aberrant metabolism
Published in Expert Review of Clinical Pharmacology, 2019
Mjriam Capula, Giulia Mantini, Niccola Funel, Elisa Giovannetti
A phase III randomized trial of The Gruppo Oncologico Nord Ovest (GONO) further demonstrated the efficacy of the simplified FOLFOXIRI regimen in metastatic colorectal cancer. This modified regimen included a higher dose of 5-FU continuous infusion and a slightly lower dose of irinotecan [27]. More recently, Vivaldi and colleagues used the GONO-FOLFOXIRI regimen (irinotecan 165 mg/m2 over 1 h, followed by oxaliplatin 85 mg/m2 and leucovorin 200 mg/m2 concomitantly over 2 h through a Y-connector, on Day-1, followed by fluorouracil 3,200 mg/m2 as a 48-h continuous infusion starting on Day-1) and a modified schedule (irinotecan 150 mg/m2 over 1 h, followed by oxaliplatin 85 mg/m2 and leucovorin 200 mg/m2 concomitantly over 2 h through a Y-connector, on Day-1, and followed by 5-FU 2,800 mg/m2 as a 48-h continuous infusion starting on Day-1) in 137 stage III/IV PDAC patients. One (0.6%) complete response and 52 (38%) partial responses were observed in the whole population, with a disease control rate of 72.2%. The median OS and median PFS were 12 and 8 months, respectively. Regarding the toxicity profile, the main hematologic grade 3–4 toxicity was neutropenia (35.7%), but only one patient (0.7%) experienced febrile neutropenia. The main G3-4 non-hematological adverse events included G3 diarrhea in 11 (8%), nausea in 10 (7.3%), stomatitis in 9 (6.5%) and liver toxicity in 6 (4.4%) patients [28].