A prospective feasibility study of uracil-tegafur and leucovorin as adjuvant chemotherapy for patients aged ≥ 80 years after curative resection of colorectal cancer, the HiSCO-03 study.
Adjuvant chemotherapy
Colorectal cancer
Elderly
Uracil–tegafur and leucovorin
Journal
Cancer chemotherapy and pharmacology
ISSN: 1432-0843
Titre abrégé: Cancer Chemother Pharmacol
Pays: Germany
ID NLM: 7806519
Informations de publication
Date de publication:
04 2023
04 2023
Historique:
received:
12
12
2022
accepted:
16
03
2023
medline:
4
4
2023
pubmed:
23
3
2023
entrez:
22
3
2023
Statut:
ppublish
Résumé
There is no consensus on the safety and effectiveness of adjuvant chemotherapy for patients with stage III colorectal cancer (CRC) aged ≥ 80 years. We conducted a prospective multi-institutional phase II study of uracil-tegafur and leucovorin (UFT/LV) as adjuvant chemotherapy in this population. Patients with stage III CRC aged ≥ 80 years who underwent curative resection were enrolled. Eligible patients received UFT/LV therapy (UFT, 300 mg/m Sixty-nine patients were enrolled between 2013 and 2021. Of the 69 patients, 65 were included in the analysis. There were 32 males and 33 females with a median age of 82 years (range 80-88 years). In the primary endpoint, administration completion rate was 67.3% (95% confidence interval 54.9-77.6%), and the lower limit of the 95% confidence interval was below the threshold of 60%. 21 patients discontinued treatment because of adverse events (AEs) and refused treatment. The median relative dose intensities were 84% (range 4-100%) for UFT, and 100% (range 4-100%) for LV. Incidence of grade three or higher AEs were neutropenia (1.5%), aspartate transaminase elevation (3%), alanine transaminase elevation (1.5%), oral mucositis (3%), anemia (1.5%), and diarrhea (4.6%). The indications for adjuvant UFT/LV therapy for elderly CRC aged ≥ 80 years were considered limited. It is necessary to clarify the background of patients in whom drug administration is discontinued and investigate their impact on long-term prognosis.
Identifiants
pubmed: 36947210
doi: 10.1007/s00280-023-04526-7
pii: 10.1007/s00280-023-04526-7
doi:
Substances chimiques
Leucovorin
Q573I9DVLP
Tegafur
1548R74NSZ
Uracil
56HH86ZVCT
Types de publication
Clinical Trial, Phase II
Journal Article
Multicenter Study
Langues
eng
Sous-ensembles de citation
IM
Pagination
317-324Informations de copyright
© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.
Références
National Cancer Institute (2022) Surveillance, epidemiology, and end results program. https://seer.cancer.gov/statfacts/html/colorect.html . Accessed 29 Oct 2022
André T, Boni C, Mounedji-Boudiaf L, Navarro M, Tabernero J, Hickish T, Topham C, Zaninelli M, Clingan P, Bridgewater J et al (2004) Oxaliplatin, fluorouracil, and leucovorin as adjuvant treatment for colon cancer. N Engl J Med 350(23):2343–2351. https://doi.org/10.1056/NEJMoa032709
doi: 10.1056/NEJMoa032709
pubmed: 15175436
Kuebler JP, Wieand HS, O’Connell MJ, Smith RE, Colangelo LH, Yothers G, Petrelli NJ, Findlay MP, Seay TE, Atkins JN et al (2007) Oxaliplatin combined with weekly bolus fluorouracil and leucovorin as surgical adjuvant chemotherapy for stage II and III colon cancer: results from NSABP C-07. J Clin Oncol 25(16):2198–2204. https://doi.org/10.1200/JCO.2006.08.2974
doi: 10.1200/JCO.2006.08.2974
pubmed: 17470851
Haller DG, O'Connell MJ, Cartwright TH, Twelves CJ, McKenna EF, Sun W, Saif MW, Lee S, Yothers G, Schmoll HJ (2015) Impact of age and medical comorbidity on adjuvant treatment outcomes for stage III colon cancer: a pooled analysis of individual patient data from four randomized, controlled trials. Ann Oncol 26(4):715–724. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4374386
Tournigand C, Andre T, Bonnetain F, Chibaudel B, Lledo G, Hickish T, Tabernero J, Boni C, Bachet JB, Teixeira L et al (2012) Adjuvant therapy with fluorouracil and oxaliplatin in stage II and elderly patients (between ages 70 and 75 years) with colon cancer: subgroup analyses of the Multicenter International Study of Oxaliplatin, Fluorouracil, and Leucovorin in the Adjuvant Treatment of Colon Cancer trial. J Clin Oncol 30(27):3353–3360. https://doi.org/10.1200/JCO.2012.42.5645
Yothers G, O'Connell MJ, Allegra CJ, Kuebler JP, Colangelo LH, Petrelli NJ, Wolmark N (2011) Oxaliplatin as adjuvant therapy for colon cancer: updated results of NSABP C-07 trial, including survival and subset analyses. J Clin Oncol 29(28):3768–3774. https://doi.org/10.1200/JCO.2011.36.4539
Twelves C, Wong A, Nowacki MP, Abt M, Burris H III, Carrato A, Cassidy J, Cervantes A, Fagerberg J, Georgoulias V et al (2005) Capecitabine as adjuvant treatment for stage III colon cancer. N Engl J Med 352(26):2696–2704. https://doi.org/10.1056/NEJMoa043116
YoYoshida M, Ishiguro M, Ikejiri K, Mochizuki I, Nakamoto Y, Kinugasa Y, Takagane A, Endo T, Shinozaki H, Takii Y et al (2014) S-1 as adjuvant chemotherapy for stage III colon cancer: a randomized phase III study (ACTS-CC trial). Ann Oncol 25(9):1743–1749. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4143094
Sadahiro S, Tsuchiya T, Sasaki K, Kondo K, Katsumata K, Nishimura G, Kakeji Y, Baba H, Sato S, Koda K et al (2015) Randomized phase III trial of treatment duration for oral uracil and tegafur plus leucovorin as adjuvant chemotherapy for patients with stage IIB/III colon cancer: final results of JFMC33-0502. Ann Oncol 26(11):2274–2280. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4621030
Shimada Y, Hamaguchi T, Mizusawa J, Saito N, Kanemitsu Y, Takiguchi N, Ohue M, Kato T, Takii Y, Sato T et al (2014) Randomised phase III trial of adjuvant chemotherapy with oral uracil and tegafur plus leucovorin versus intravenous fluorouracil and levofolinate in patients with stage III colorectal cancer who have undergone Japanese D2/D3 lymph node dissection: final results of JCOG0205. Eur J Cancer 50(13):2231–2240. https://www.sciencedirect.com/science/article/pii/S0959804914007242
Shimomura M, Ikeda S, Nakahara M, Adachi T, Saitoh Y, Shimizu Y, Toyota K, Ishizaki Y, Yoshimitsu M, Takakura Y et al (2023) Prospective cohort study of patients with stage III colorectal cancer aged ≥ 80 years who underwent curative resection: the HiSCO-04 study. J Clin Oncol 41(Suppl 4: Abstr 1):26s
Dindo D, Demartines N, Clavien PA (2004) Classification of surgical complications: a new proposal with evaluation in a cohort of 6336 patients and results of a survey. Ann Surg 240(2):205–213. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1360123
World Health Organization (2022) The global health observatory. https://www.who.int/data/gho . Accessed 29 Oct 2022
Ministry of Health, Labour and Welfare (2022) Summary of the 2010 simplified life tables. https://www.mhlw.go.jp/toukei/saikin/hw/life/life10/01.html . Accessed 29 Oct 2022
Sargent DJ, Goldberg RM, Jacobson SD, Macdonald JS, Labianca R, Haller DG, Shepherd LE, Seitz JF, Francini G (2001) A pooled analysis of adjuvant chemotherapy for resected colon cancer in elderly patients. N Engl J Med 345(15):1091–1097. https://doi.org/10.1056/NEJMoa010957
Mochizuki I, Takiuchi H, Ikejiri K, Nakamoto Y, Kinugasa Y, Takagane A, Endo T, Shinozaki H, Takii Y, Takahashi Y et al (2012) Safety of UFT/LV and S-1 as adjuvant therapy for stage III colon cancer in phase III trial: ACTS-CC trial. Br J Cancer 106(7):1268–1273. https://www.nature.com/articles/bjc201286
Lembersky BC, Wieand HS, Petrelli NJ, O'Connell MJ, Colangelo LH, Smith RE, Seay TE, Giguere JK, Marshall ME, Jacobs AD et al (2006) Oral uracil and tegafur plus leucovorin compared with intravenous fluorouracil and leucovorin in stage II and III carcinoma of the colon: results from National Surgical Adjuvant Breast and Bowel Project Protocol C-06. J Clin Oncol 24(13):2059–2064. https://doi.org/10.1200/JCO.2005.04.7498
Ellis G, Whitehead MA, O'Neill D, Langhorne P, Robinson D (2011) Comprehensive geriatric assessment for older adults admitted to hospital. Cochrane Database Syst Rev (7):CD006211. https://www.bmj.com/content/343/bmj.d6553.long
Kalsi T, Babic-Illman G, Ross PJ, Maisey NR, Hughes S, Fields P, Martin FC, Wang Y, Harari D (2015) The impact of comprehensive geriatric assessment interventions on tolerance to chemotherapy in older people. Br J Cancer 112(9):1435–1444. https://www.nature.com/articles/bjc2015120
Puts MT, Hardt J, Monette J, Girre V, Springall E, Alibhai SM (2012) Use of geriatric assessment for older adults in the oncology setting: a systematic review. J Natl Cancer Inst 104(15):1133–1163. https://academic.oup.com/jnci/article/104/15/1134/949848
Wildiers H, Heeren P, Puts M, Topinkova E, Janssen-Heijnen ML, Extermann M, Falandry C, Artz A, Brain E, Colloca G et al (2014) International Society of Geriatric Oncology consensus on geriatric assessment in older patients with cancer. J Clin Oncol 32(24):2595–2603. https://doi.org/10.1200/JCO.2013.54.8347
Antonio M, Saldana J, Carmona-Bayonas A, Navarro V, Tebe C, Nadal M, Formiga F, Salazar R, Borras JM (2017) Geriatric assessment predicts survival and competing mortality in elderly patients with early colorectal cancer: Can it help in adjuvant therapy decision-making? Oncologist 22(8):934–943. https://www.nature.com/articles/bjc2017455
Vallet-Regi M, Manzano M, Rodriguez-Manas L, Checa Lopez M, Aapro M, Balducci L (2017) Management of cancer in the older age person: an approach to complex medical decisions. Oncologist 22(3):335–342. https://doi.org/10.1634/theoncologist.2016-0276
Lund CM, Vistisen KK, Olsen AP, Bardal P, Schultz M, Dolin TG, Ronholt F, Johansen JS, Nielsen DL (2021) The effect of geriatric intervention in frail older patients receiving chemotherapy for colorectal cancer: a randomised trial (GERICO). Br J Cancer 124(12):1949–1958. https://www.nature.com/articles/s41416-021-01367-0