Colorectal cancer
Pat Price, Karol Sikora in Treatment of Cancer, 2014
Unfortunately, other doublet combinations with 5-FU, such as irinotecan and triplets, with the addition of biological agents (the anti-EGFR antibody cetuximab and the anti-VEGF antibody bevacizumab, which are also discussed under metastatic tumour therapy), have disappointingly not shown any additional benefits over MOSAIC in large randomized studies. Thus, the standard of care for adjuvant chemotherapy remains FOLFOX (or its equivalent CAPOX) for Dukes C colon cancer. For Dukes B cancer, the risk assessment can favour no adjuvant treatment versus monotherapy with capecitabine or 5-FU or in higher risk patients (at the potential expense of a risk of permanent neuropathy) FOLFOX or CAPOX. For the latter, there has been no prospective randomized study unequivocally demonstrating the additional benefit of oxaliplatin, even in the higher risk Dukes B patients. Newer risk assessment tools using molecular signatures are now available but are still to be validated prospectively and do not have general acceptance as yet.
Colorectal Cancer
Pat Price, Karol Sikora in Treatment of Cancer, 2020
Since the pivotal MOSAIC trial, no further progress in improving overall survival in unselected Dukes’ B and C patients has been made. The addition of a third agent to FOLFOX, either cetuximab or bevacizumab, was not superior. Neither was their equivalence when switching from oxaliplatin to irinotecan. However, approaches to reduce treatment toxicity and improve the quality of life in patients by giving shorter-duration FOLFOX or CAPOX chemotherapy have been successfully tested. In the United Kingdom, the SCOT trial, which was also part of a larger global initiative (the IDEA collaboration), demonstrates that 3 months duration versus the standard 6 months, in most subsets of patients, is a non-inferior approach with a significant reduction in neuropathy risk, improved quality of life, and improved health economics.180
Radical Sphincter-Sparing Resection in Rectal Cancer
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 in Keighley & Williams’ Surgery of the Anus, Rectum and Colon, 2019
An alternative strategy for locally advanced tumours was evaluated in the single-arm EXPERT trial.349 The trial administered capecitabine with oxaliplatin (CAPOX) prior to pre-operative CRT followed by TME and 12 weeks of adjuvant therapy in high-risk rectal cancer patients (optimal MRI – <1 mm tumour from mesorectal fascia, unsafe mrLRP, extramural venous invasion). The three- and five-year progression-free survival were 68% and 64% respectively and overall survival rates 83% and 75% respectively.349 The trial was followed by the EXPERT-C multicentre phase II RCT; the design included four cycles of pre-operative CAPOX prior to pre-operative CRT and randomisation to have or not have Cetuximab.350 One hundred and sixty-five eligible patients were randomised. Ninety (60%) of 149 were KRAS or BRAF wild type (1:1 randomised CAPOX n = 44, CAPOX-C n = 46), and in these patients, the addition of cetuximab did not improve the primary end point of complete response (9% vs 11%, respectively) but cetuximab significantly improved the response rate (post-CRT by RECIST criteria: CAPOX 75% vs CAPOX-C 93%, p = 0.028) and overall survival (HR, 0.27; p = 0.034). Skin toxicity and diarrhoea were more frequent in the CAPOX-C arm. The combined overall survival was 85% at three-year follow-up.350
Performance of capecitabine in novel combination therapies in colorectal cancer
Published in Journal of Chemotherapy, 2021
Fahima Danesh Pouya, Yousef Rasmi, Irem Yalim Camci, Yusuf Tutar, Mohadeseh Nemati
OX is a non-nephrotoxic third-generation platinum-based chemotherapeutic agent used to treat CRC. If used as a single drug, the RR is between 10% and 20%23,24 and is inactive in second-line treatment for CRC patients.25 OX inhibits DNA replication and DNA transcription by binding intrastrand between two adjacent guanine residues or guanine and an adenine.26 Preclinical data suggest a synergistic interaction between OX and fluoropyrimidines.27 Also, CAP and OX (CAPOX) could potentially be co-administered because of their overlapping toxicity. Nishimura et al.28 in Phase II clinical trial, examined only the performance of chemotherapy combination of CAPOX in locally advanced rectal and have reported that CAPOX following mesorectal excision may be a safe treatment strategy. In Phase III studies, OX in combination with CAP showed similar efficacy and safety as folinic acid, fluorouracil, and OX (FOLFOX) as first-line therapy for mCRC (Figure 1, Table 1).29
The consensus Immunoscore in phase 3 clinical trials; potential impact on patient management decisions
Published in OncoImmunology, 2020
Franck Pagès, Julien Taieb, Pierre Laurent-Puig, Jérôme Galon
The feasibility, robustness, and reproducibility of Immunoscore are essential steps for its integration in clinical practice. In a routine practice for prospective cases, the Immunoscore success rate exceeds 90% without retesting and 95% after retesting. Indeed, the analytical validity of Immunoscore was recently published.12,13 A limitation of our study is that 90% of patients in the IDEA France study were treated with the FOLFOX-regimen, precluding from any conclusion for patients receiving CAPOX. Furthermore, these important predictive results should be further validated in additional IDEA studies. Finally, ctDNA assessment after surgery seems to be a relevant marker of minimal residual disease and to stratify patients for their relapse risk and may bear complementary information to help guiding clinical decision.
Adjuvant therapy for resected colon cancer 2017, including the IDEA analysis
Published in Expert Review of Anticancer Therapy, 2018
Monica Tang, Timothy Jay Price, Jeremy Shapiro, Peter Gibbs, Daniel G. Haller, Dirk Arnold, Marc Peeters, Eva Segelov, Amitesh Roy, Niall Tebbutt, Nick Pavlakis, Chris Karapetis, Matthew Burge
Fluoropyrimidines and oxaliplatin remain the backbone for adjuvant treatment of Stage III colon cancer, with 5-FU and capecitabine both acceptable agents to combine with oxaliplatin.Single agent fluoropyrimidine is an acceptable choice for patients at high risk of toxicities and/or are likely to derive low absolute benefits from doublet chemotherapy.The IDEA collaboration meta-analysis provides evidence that 3 months of adjuvant oxaliplatin-based chemotherapy is reasonable in low-risk resected Stage III colon cancer, in which case CAPOX is the preferred regimen. This will result in substantial benefits for quality of life and health care costs.In high risk Stage III patients, defined as T4 and/or N2, if FOLFOX is the chosen adjuvant regimen, 6 months’ treatment is preferred. If using CAPOX, 3 months is reasonable, although continuing to 6 months may be considered, particularly in those with T4 primary tumors. Clinicians should have careful discussions with patients regarding the absolute benefits and potential toxicities of treatment when making decisions regarding the choice and duration of adjuvant chemotherapy.There is currently insufficient information regarding optimal duration of adjuvant chemotherapy in resected Stage II colon cancer patients.
Related Knowledge Centers
- Capecitabine
- Chemotherapy Regimen
- Oxaliplatin
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