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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).
Radical Sphincter-Sparing Resection in Rectal Cancer
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
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
Colorectal cancer
Published in Pat Price, Karol Sikora, 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.
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
Efficacy of adjuvant cytokine-induced killer cell immunotherapy in patients with colorectal cancer after radical resection
Published in OncoImmunology, 2020
Qiu-Zhong Pan, Jing-Jing Zhao, Chao-Pin Yang, Yu-Qing Zhou, Jun-Zhong Lin, Yan Tang, Jia-Mei Gu, Qi-Jing Wang, Yong-Qiang Li, Jia He, Shi-Ping Chen, Meng-Jia Song, Yue Huang, Jie-Ying Yang, De-Sheng Weng, Jian-Chuan Xia
All patients underwent completion resection. Following surgery, all patients in the control and CIK groups received adjuvant chemotherapy with FOLFOX (bolus and infused fluorouracil with oxaliplatin), CAPOX (oxaliplatin and capecitabine), or single-agent capecitabine regimen. For patients receiving FOLFOX, treatment was given every 2 weeks with the intention of delivering twelve cycles to patients assigned 24 weeks of therapy. For patients receiving CAPOX or single-agent capecitabine, treatment was given every 3 weeks with an intention of delivering eight cycles to patients assigned 24 weeks of therapy. The duration of chemotherapy included neoadjuvant and adjuvant treatment stage (Supplementary Table S1). Dose reductions or treatment delays were calculated according to the treatment- related adverse events, which were graded according to the National Cancer Institute Common Toxicity Criteria for Adverse Events version 4.0.
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.