Raadpleeg ook literatuurlijst niet-toxische stoffen en behandelingen specifiek bij vormen van darmkanker van arts-bioloog drs. Engelbert Valstar.

Zie ook gerelateerde artikelen voor effectiviteit van de verschillende vormen van chemo voor darmkanker.

7 oktober 2019: Bron: Journal of Clinical Oncology

Standaard eerstelijns voor uitgezaaide endeldarmkanker is vooraf aan een operatie 4 tot 6 kuren met chemo plus eventueel radiotherapie. En na operatie nog eens 4 tot 6 kuren met chemotherapie. Heel veel patienten krijgen als chemo mFOLFOX6 die is samengesteld met gemodificeerde fluorouracil via infuus, leucovorin, en oxaliplatin. Echter uit een fase III studie blijkt nu dat de toevoeging van oxaliplatin geen enkel effect heeft op de 3-jaars overall overleving en de kans op een recidief.

In een Chinese multicenter, open-label, fase III-studie, werden mFOLFOX6 (gemodificeerd infuus fluorouracil, leucovorin en oxaliplatin) met of zonder radiotherapie versus infuus fluorouracil plus radiotherapie geëvalueerd in de neoadjuvante setting voor de behandeling van 495 patiënten met stadium II / III rectumkanker.

Ondanks de toevoeging van oxaliplatine, was de 3-jaars kans op lokaal recidief na R0 / R1-resectie en de 3-jaars totale overleving vergelijkbaar in alle drie de groepen. Respectievelijk: 91.3%, 89.1%, and 90.7% (P = .971 by log-rank test)

Ook was er geen verschil tussen wel of geen radiotherapie naast oxaliplatin. Ondanks dat mFOLFOX6 wel een betere respons gaf op de behandeling vooraf aan de operatie was de overall overleving en kans op een recidief gelijk bij alle drie de groepen. 

Hier de grafieken van de drie groepen:

Figure

FIG 2.Kaplan-Meier estimates of (A) disease-free survival (DFS), (B) locoregional recurrence after R0/1 resection, and (C) overall survival (OS) in the intention-to-treat population. FU, fluorouracil; HR, hazard ratio; mFOLFOX6, modified infusional fluorouracil, leucovorin, and oxaliplatin; RT, radiotherapy.

Het volledige studierapport is gratis in te zien: Neoadjuvant Modified FOLFOX6 With or Without Radiation Versus Fluorouracil Plus Radiation for Locally Advanced Rectal Cancer: Final Results of the Chinese FOWARC Trial

Hier het abstract van de studie:

Neoadjuvant Modified FOLFOX6 With or Without Radiation Versus Fluorouracil Plus Radiation for Locally Advanced Rectal Cancer: Final Results of the Chinese FOWARC Trial

Yanhong Deng, MD, PhD1; Pan Chi, MD2; Ping Lan, MD, PhD1; Lei Wang, PhD1†; Weiqing Chen, MD, PhD3; Long Cui, MD4; ...Show More

†Deceased.

Y.D., P.C., and P.L. contributed equally to the article.

Creative Commons Attribution Non-Commercial No Derivatives 4.0 License: https://creativecommons.org/licenses/by-nc-nd/4.0/

ABSTRACT

PURPOSE

In the multicenter, open-label, phase III FOWARC trial, modified infusional fluorouracil, leucovorin, and oxaliplatin (mFOLFOX6) plus radiotherapy resulted in a higher pathologic complete response rate than fluorouracil plus radiotherapy in Chinese patients with locally advanced rectal cancer. Here, we report the final results.

METHODS

Adults ages 18 to 75 years with stage II/III rectal cancer were randomly assigned (1:1:1) to five cycles of infusional fluorouracil (leucovorin 400 mg/m2, fluorouracil 400 mg/m2, and fluorouracil 2.4 g/m2 over 48 hours) plus radiotherapy (46.0 to 50.4 Gy delivered in 23 to 25 fractions during cycles 2 to 4) followed by surgery and seven cycles of infusional fluorouracil, the same treatment plus intravenous oxaliplatin 85 mg/m2 on day 1 of each cycle (mFOLFOX6), or four to six cycles of mFOLFOX6 followed by surgery and six to eight cycles of mFOLFOX6. The primary end point was 3-year disease-free survival (DFS).

RESULTS

In total, 495 patients were randomly assigned to treatment. After a median follow-up of 45.2 months, DFS events were reported in 46, 39, and 46 patients in the fluorouracil plus radiotherapy, mFOLFOX6 plus radiotherapy, and mFOLFOX6 arms. In each arm, the probability of 3-year DFS was 72.9%, 77.2%, and 73.5% (P = .709 by the log-rank test), the 3-year probability of local recurrence after R0/1 resection was 8.0%, 7.0%, and 8.3% (P = .873 by the log-rank test), and the 3-year overall survival rate was 91.3%, 89.1%, and 90.7% (P = .971 by log-rank test), respectively.

CONCLUSION

mFOLFOX6, with or without radiation, did not significantly improve 3-year DFS versus fluorouracil with radiation in patients with locally advanced rectal cancer. No significant difference in outcomes was found between mFOLFOX6 without radiotherapy and fluorouracil with radiotherapy, which requires additional investigation of the role of radiotherapy in these regimens.

REFERENCES
1. Benson AB III, Venook AP, Al-Hawary MM, et al: Rectal cancer, version 2.2018, NCCN Clinical Practice Guidelines in Oncology. J Natl Compr Canc Netw 16:874-901, 2018 Crossref, Google Scholar
2. Gérard JP, Conroy T, Bonnetain F, et al: Preoperative radiotherapy with or without concurrent fluorouracil and leucovorin in T3-4 rectal cancers: Results of FFCD 9203. J Clin Oncol 24:4620-4625, 2006 Link, Google Scholar
3. De Caluwé L, Van Nieuwenhove Y, Ceelen WP: Preoperative chemoradiation versus radiation alone for stage II and III resectable rectal cancer. Cochrane Database Syst Rev (2):CD006041, 2013 Google Scholar
4. McCarthy K, Pearson K, Fulton R, et al: Pre-operative chemoradiation for non-metastatic locally advanced rectal cancer. Cochrane Database Syst Rev 12:CD008368, 2012 Google Scholar
5. Rahbari NN, Elbers H, Askoxylakis V, et al: Neoadjuvant radiotherapy for rectal cancer: Meta-analysis of randomized controlled trials. Ann Surg Oncol 20:4169-4182, 2013 Crossref, Medline, Google Scholar
6. Aschele C, Cionini L, Lonardi S, et al: Primary tumor response to preoperative chemoradiation with or without oxaliplatin in locally advanced rectal cancer: Pathologic results of the STAR-01 randomized phase III trial. J Clin Oncol 29:2773-2780, 2011 Link, Google Scholar
7. Allegra CJ, Yothers G, O’Connell MJ, et al: Neoadjuvant 5-FU or capecitabine plus radiation with or without oxaliplatin in rectal cancer patients: A phase III randomized clinical trial. J Natl Cancer Inst 107:djv248, 2015 Crossref, Google Scholar
8. Azria D, Doyen J, Jarlier M, et al: Late toxicities and clinical outcome at 5 years of the ACCORD 12/0405-PRODIGE 02 trial comparing two neoadjuvant chemoradiotherapy regimens for intermediate-risk rectal cancer. Ann Oncol 28:2436-2442, 2017 Crossref, Google Scholar
9. Rödel C, Graeven U, Fietkau R, et al: Oxaliplatin added to fluorouracil-based preoperative chemoradiotherapy and postoperative chemotherapy of locally advanced rectal cancer (the German CAO/ARO/AIO-04 study): Final results of the multicentre, open-label, randomised, phase 3 trial. Lancet Oncol 16:979-989, 2015 Crossref, Medline, Google Scholar
10. Rödel C, Liersch T, Becker H, et al: Preoperative chemoradiotherapy and postoperative chemotherapy with fluorouracil and oxaliplatin versus fluorouracil alone in locally advanced rectal cancer: Initial results of the German CAO/ARO/AIO-04 randomised phase 3 trial. Lancet Oncol 13:679-687, 2012 Crossref, Medline, Google Scholar
11. Peeters KC, van de Velde CJ, Leer JW, et al: Late side effects of short-course preoperative radiotherapy combined with total mesorectal excision for rectal cancer: Increased bowel dysfunction in irradiated patients–a Dutch colorectal cancer group study. J Clin Oncol 23:6199-6206, 2005 Link, Google Scholar
12. Lange MM, den Dulk M, Bossema ER, et al: Risk factors for faecal incontinence after rectal cancer treatment. Br J Surg 94:1278-1284, 2007 Crossref, Medline, Google Scholar
13. Bruheim K, Guren MG, Skovlund E, et al: Late side effects and quality of life after radiotherapy for rectal cancer. Int J Radiat Oncol Biol Phys 76:1005-1011, 2010 Crossref, Medline, Google Scholar
14. Jalil O, Claydon L, Arulampalam T: Review of neoadjuvant chemotherapy alone in locally advanced rectal cancer. J Gastrointest Cancer 46:219-236, 2015 Crossref, Google Scholar
15. Deng Y, Chi P, Lan P, et al: Modified FOLFOX6 with or without radiation versus fluorouracil and leucovorin with radiation in neoadjuvant treatment of locally advanced rectal cancer: Initial results of the Chinese FOWARC multicenter, open-label, randomized three-arm phase III trial. J Clin Oncol 34:3300-3307, 2016 Link, Google Scholar
16. Ryan R, Gibbons D, Hyland JM, et al: Pathological response following long-course neoadjuvant chemoradiotherapy for locally advanced rectal cancer. Histopathology 47:141-146, 2005 Crossref, Medline, Google Scholar
17. Zheng J, Feng X, Hu W, et al: Systematic review and meta-analysis of preoperative chemoradiotherapy with or without oxaliplatin in locally advanced rectal cancer. Medicine (Baltimore) 96:e6487, 2017 Crossref, Google Scholar
18. André T, Boni C, Mounedji-Boudiaf L, et al: Oxaliplatin, fluorouracil, and leucovorin as adjuvant treatment for colon cancer. N Engl J Med 350:2343-2351, 2004 Crossref, Medline, Google Scholar
19. Lefevre JH, Mineur L, Cachanado M, et al: Does a longer waiting period after neoadjuvant radiochemotherapy improve the oncological prognosis of rectal cancer?: Three-year follow-up results of the GRECCAR-6 randomized multicenter trial. J Clin Oncol 37, 2019 (suppl; abstr 483) Google Scholar
20. Gérard JP, Azria D, Gourgou-Bourgade S, et al: Comparison of two neoadjuvant chemoradiotherapy regimens for locally advanced rectal cancer: Results of the phase III trial ACCORD 12/0405-Prodige 2. J Clin Oncol 28:1638-1644, 2010 Link, Google Scholar
21. Schmoll H-J, Haustermans K, Price T, et al: Preoperative chemoradiotherapy and postoperative chemotherapy with capecitabine and oxaliplatin versus capecitabine alone in locally advanced rectal cancer: Disease-free survival results at interim analysis. Proc Am Soc Clin Oncol 32:3501, 2014 Google Scholar
22. Jiao D, Zhang R, Gong Z, et al: Fluorouracil-based preoperative chemoradiotherapy with or without oxaliplatin for stage II/III rectal cancer: A 3-year follow-up study. Chin J Cancer Res 27:588-596, 2015 Google Scholar
23. Bernier L, Balyasnikova S, Tait D, et al: Watch-and-wait as a therapeutic strategy in rectal cancer. Curr Colorectal Cancer Rep 14:37-55, 2018 Crossref, Google Scholar
24. Kim CH, Lee SY, Kim HR, et al: Prognostic effect of pretreatment serum carcinoembryonic antigen level: A useful tool for prediction of distant metastasis in locally advanced rectal cancer following neoadjuvant chemoradiotherapy and total mesorectal excision. Medicine (Baltimore) 94:e1291, 2015 Crossref, Google Scholar
25. Lee JH, Kim SH, Jang HS, et al: Preoperative elevation of carcinoembryonic antigen predicts poor tumor response and frequent distant recurrence for patients with rectal cancer who receive preoperative chemoradiotherapy and total mesorectal excision: A multi-institutional analysis in an Asian population. Int J Colorectal Dis 28:511-517, 2013 Google Scholar
26. Yang KL, Yang SH, Liang WY, et al: Carcinoembryonic antigen (CEA) level, CEA ratio, and treatment outcome of rectal cancer patients receiving pre-operative chemoradiation and surgery. Radiat Oncol 8:43, 2013 Crossref, Google Scholar
27. Sung S, Son SH, Kay CS, et al: Prognosis can be predicted more accurately using pre- and postchemoradiotherapy carcinoembryonic antigen levels compared to only prechemoradiotherapy carcinoembryonic antigen level in locally advanced rectal cancer patients who received neoadjuvant chemoradiotherapy. Medicine (Baltimore) 95:e2965, 2016 Google Scholar

mFOLFOX6, fluorouracil, leucovorin, oxaliplatin, endeldarmkanker, overall overleving, radiotherapie


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