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Small-Molecule Targeted Therapies
Published in David E. Thurston, Ilona Pysz, Chemistry and Pharmacology of Anticancer Drugs, 2021
Aflibercept, also known in the US as ziv-aflibercept, was approved by the FDA in 2011 for the treatment of wet macular degeneration in the eye, followed by approval in 2012 for use in combination with FOLFIRI for the treatment of metastatic colorectal cancer resistant to, or has progressed following, an oxaliplatin-containing regimen. It is now marketed under the trade name of Eylea™ for wet macular degeneration, and Zaltrap™ for metastatic colorectal cancer. In the UK it is recommended by NICE in combination with irinotecan, fluorouracil, and folinic acid (FOLFIRI) chemotherapy for the treatment of metastatic colorectal cancer resistant to an oxaliplatin-containing regimen.
Colorectal Cancer
Published in Pat Price, Karol Sikora, Treatment of Cancer, 2020
Combinations of irinotecan with 5-FU and FA showed synergy in pre-clinical studies, and clinical combination regimens were developed and have become a standard of care globally. Randomized comparison of the combination with 5-infusional FU and FA showed significantly higher response rates for the combination in two trials146,147 and a survival improvement of 17.4 versus 14.1 months. A 2-weekly combination with infusional 5-FU/FA (FOLFIRI) is favored over the original 3-weekly irinotecan monotherapy due to increased diarrheal toxicity with the latter.
Effects of treatment on the abdomen and pelvis
Published in Anju Sahdev, Sarah J. Vinnicombe, Husband & Reznek's Imaging in Oncology, 2020
Chemotherapy effects on the bowel mainly occur early following treatment (Table 39.3). Benign non-specific small bowel thickening is seen with many agents manifested by smooth thickening of the valvulae conniventes without evidence of any free fluid, obstruction, or inflammatory changes (Figure 39.11a). Enteritis may be diffuse or limited to the terminal ileum. Chemotherapeutic regimens like FOLFIRI, i.e. folinic acid (leucovorin) with fluorouracil (5-FU) and irinotecan, increase the risk. This is seen as hyperaemia with submucosal oedema producing a ‘target sign’ on CT (36) (Figure 39.11b). Neutropenic enterocolitis results from chemotherapy-induced mucosal injury and secondary superinfection, most commonly associated with treatment of acute leukaemia. Typhlitis is the localized form limited to the caecum (Figure 39.12).
Telmisartan Influences the Antiproliferative Activity of Linoleic Acid in Human Colon Cancer Cells
Published in Nutrition and Cancer, 2020
Magdalena Mielczarek-Puta, Dagmara Otto-Ślusarczyk, Alicja Chrzanowska, Agnieszka Filipek, Wojciech Graboń
Colorectal cancer (CRC) is the third most common malignancy and the fourth lethal disease worldwide. In recent decades, the incidence and mortality rates of CRC in Eastern Europe, Latin America, and Asia significant increased. Moreover, the risk of developing CRC depends on age (1). The most common treatment for CRC is chemo- and radiotherapy often given after tumor resection. FOLFIRI and FOLFOX regimens commonly used in colon cancer chemotherapy prolong the survival period over 20 months. However, 40% of patients with disease progression after a first line of treatment cannot undergo long-term therapy because of deterioration of their performance condition or liver function (2). Therefore, it seems important to find other agents that can be administrated every day and selectively affect cancer cells through time- and cell-specific effect. Literature data have been reported that polyunsaturated fatty acids (PUFAs) possess selectively tumoricidal action (3–5). Numerous epidemiological and animal experimental studies have shown that PUFAs have growth-inhibitory and pro-apoptotic effects on colon cancer cells such as HT-29, HCT116, SW480, SW620, and Caco-2 (6–10). One of the important PUFAs commonly present in diet is linoleic acid ((LA), n-6, 18:2) (11). In vivo and in vitro studies suggested that LA induced apoptosis in cancer cells by free radical generation and mitochondrial dysfunction as well as by PPARgamma activation (12,13).
KRAS codon 12 and 13 mutations may guide the selection of irinotecan or oxaliplatin in first-line treatment of metastatic colorectal cancer
Published in Expert Review of Molecular Diagnostics, 2019
Yakup Ergun, Yusuf Acikgoz, Oznur Bal, Gokhan Ucar, Merve Dirikoc, Eda Caliskan Yildirim, Nadiye Akdeniz, Dogan Uncu
The first-line treatment of patients was one of the following regimens, FUFA, modified FOLFOX6 or FOLFIRI. The FUFA regimen comprised folinic acid 400 mg/m2/day administered as a 2-h infusion, followed by a 10-min bolus 5-FU 400 mg/m2, and a 46-h continuous infusion of 5-FU, 2400 mg/m2. The FOLFOX combination included oxaliplatin 85 mg/m2 in 250 mL of dextrose 5%, concurrent with FA 400 mg/m2/day administered as a 2-h intravenous infusion, followed by a 10-min bolus 5-FU 400 mg/m2, and a 46-h continuous infusion of 5-FU 2400 mg/m2. The FOLFIRI combination regimen comprised irinotecan 180 mg/m2, followed by FA 400 mg/m2 in a 2-h infusion, and then by a 10-min bolus 5-FU 400 mg/m2, and a 46-h continuous infusion of 5-FU 2400 mg/m2. For patients receiving anti-VEGF treatment, bevacizumab was administrated either with FOLFOX or FOLFIRI regimens at a dose of 5 mg/kg. For patients receiving anti-EGFR, cetuximab (500 mg/m2) or panitumumab (6 mg/kg) was administrated with either FOLFOX or FOLFIRI regimens. The cycles were repeated every 2 weeks.
Choosing the right strategy based on individualized treatment effect predictions: combination versus sequential chemotherapy in patients with metastatic colorectal cancer
Published in Acta Oncologica, 2019
Johannes J. M. Kwakman, Rob C. M. van Kruijsdijk, Sjoerd G. Elias, Matthew T. Seymour, Angela M. Meade, Frank L. J. Visseren, Cornelis J. A. Punt, Miriam Koopman
Data of the FOCUS trial were used for the external validation of the models. In FOCUS, 2135 patients were randomized between (a) first-line treatment 5-fluorouracil (5-FU) and second-line irinotecan, (b) first-line treatment 5-FU and second-line 5-FU plus irinotecan (FOLFIRI) or 5-FU plus oxaliplatin (FOLFOX), or (c) upfront combination chemotherapy with FOLFIRI or FOLFOX. For the model predicting survival times, arm A (sequential chemotherapy) and arm C (combination chemotherapy) were included. For the model predicting the probability of receiving second-line treatment arm A and B were used.