دورية أكاديمية
Metformin plus lrinotecan in patients with refractory colorectal cancer: a phase 2 clinical trial.
العنوان: | Metformin plus lrinotecan in patients with refractory colorectal cancer: a phase 2 clinical trial. |
---|---|
المؤلفون: | Bragagnoli AC; Hospital de Câncer de Barretos, Barretos, SP, Brazil. aryscampos@yahoo.com.br., Araujo RLC; Hospital de Câncer de Barretos, Barretos, SP, Brazil.; Universidade Federal de São Paulo, São Paulo, SP, Brazil.; Hospital Israelita Albert Einstein, São Paulo, SP, Brazil., Ferraz MW; Hospital de Câncer de Barretos, Barretos, SP, Brazil., Dos Santos LV; Beneficência Portuguesa de São Paulo, São Paulo, SP, Brazil., Abdalla KC; Fundação Faculdade Regional de Medicina de São José do Rio Preto, São José do Rio Preto, SP, Brazil., Comar F; Aliança Instituto de Oncologia, Brasília, DF, Brazil., Santos FA; Hospital de Câncer de Barretos, Barretos, SP, Brazil., Oliveira MA; Hospital de Câncer de Barretos, Barretos, SP, Brazil., Carvalheira JBC; Universidade Estadual de Campinas, Campinas, SP, Brazil., Cárcano FM; Hospital de Câncer de Barretos, Barretos, SP, Brazil., da Silveira Nogueira Lima JP; AC Camargo Cancer Center, São Paulo, SP, Brazil. |
المصدر: | British journal of cancer [Br J Cancer] 2021 Mar; Vol. 124 (6), pp. 1072-1078. Date of Electronic Publication: 2021 Jan 04. |
نوع المنشور: | Clinical Trial, Phase II; Journal Article; Research Support, Non-U.S. Gov't |
اللغة: | English |
بيانات الدورية: | Publisher: Nature Publishing Group on behalf of Cancer Research UK Country of Publication: England NLM ID: 0370635 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1532-1827 (Electronic) Linking ISSN: 00070920 NLM ISO Abbreviation: Br J Cancer Subsets: MEDLINE |
أسماء مطبوعة: | Publication: 2002- : London : Nature Publishing Group on behalf of Cancer Research UK Original Publication: London, Lewis. |
مواضيع طبية MeSH: | Antineoplastic Combined Chemotherapy Protocols/*therapeutic use , Colorectal Neoplasms/*drug therapy , Neoplasm Recurrence, Local/*drug therapy, Adult ; Aged ; Colorectal Neoplasms/pathology ; Female ; Follow-Up Studies ; Humans ; Irinotecan/administration & dosage ; Male ; Metformin/administration & dosage ; Middle Aged ; Neoplasm Recurrence, Local/pathology ; Prognosis ; Survival Rate ; Young Adult |
مستخلص: | Background: Patients with refractory colorectal (CRC) cancer have few treatment options. This trial tests the combination of metformin and irinotecan in this setting. Methods: A phase 2 single-arm trial was conducted, patients received metformin 2500 mg orally a day plus irinotecan 125 mg/m 2 intravenously weekly D1 and D8 every 21 days. The primary endpoint was the disease control rate according to the Response Evaluation Criteria in Solid Tumors version 1.1 at 12 weeks. Results: Between December 2015 and January 2018, 41 patients were enrolled. Seventeen patients (41%) met the primary endpoint of disease control in 12 weeks; hence, the study was deemed positive. The median progression-free survival was 3.3 months (CI 95%, 2.0-4.5 months), and the median overall survival was 8.4 months (CI 95%, 5.9-10.8 months). Both mutation RAS status and disease control at 12 weeks impacted overall survival in the multivariate model (HR 2.28, CI 95%, 1.12-4.7, p = 0.02; and HR 0.21, CI 95%, 0.08-0.5, p = 0.001, respectively). The most common adverse event was diarrhoea (29.2% grade 3). Conclusions: In this trial, metformin plus irinotecan demonstrated disease control in patients with refractory CRC. Further trials with optimised diarrhoea control are needed to confirm these results. |
References: | Bray, F., Ferlay, J., Soerjomataram, I., Siegel, R. L., Torre, L. A. & Jemal, A. J. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J. Clin. 68, 394–424 (2018). (PMID: 10.3322/caac.21492) Van Cutsem, E., Cervantes, A., Adam, R., Sobrero, A., Van Krieken, J. H., Aderka, D. et al. ESMO consensus guidelines for the management of patients with metastatic colorectal cancer. Ann. Oncol. 27, 1386–1422 (2016). (PMID: 10.1093/annonc/mdw235) Grothey, A., Van Cutsem, E., Sobrero, A., Siena, S., Falcone, A., Ychou, M. et al. Regorafenib monotherapy for previously treated metastatic colorectal cancer (CORRECT): an international, multicentre, randomised, placebo-controlled, phase 3 trial. Lancet 381, 303–312 (2013). (PMID: 10.1016/S0140-6736(12)61900-X) Mayer, R. J., Van Cutsem, E., Falcone, A., Yoshino, T., Garcia-Carbonero, R., Mizunuma, N. et al. Randomized trial of TAS-102 for refractory metastatic colorectal cancer. N. Engl. J. Med. 372, 1909–1919 (2015). (PMID: 10.1056/NEJMoa1414325) Pfeiffer, P., Yilmaz, M., Moller, S., Zitnjak, D., Krogh, M., Petersen, L. N. et al. TAS-102 with or without bevacizumab in patients with chemorefractory metastatic colorectal cancer: an investigator-initiated, open-label, randomised, phase 2 trial. Lancet Oncol. 21, 412–420 (2020). (PMID: 10.1016/S1470-2045(19)30827-7) Mei, Z. B., Zhang, Z. J., Liu, C. Y., Liu, Y., Cui, A., Liang, Z. L. et al. Survival benefits of metformin for colorectal cancer patients with diabetes: a systematic review and meta-analysis. PLoS ONE 9, e91818 (2014). (PMID: 10.1371/journal.pone.0091818) Fernández-Fernández, F. J. Antineoplastic potential of metformin in colorectal cancer. Eur. J. Intern. Med. 37, e22 (2017). (PMID: 10.1016/j.ejim.2016.08.034) Henderson, D., Frieson, D., Zuber, J. & Solomon, S. S. Metformin has positive therapeutic effects in colon cancer and lung cancer. Am. J. Med. Sci. 354, 246–251 (2017). (PMID: 10.1016/j.amjms.2017.05.006) Higurashi, T., Hosono, K., Takahashi, H., Komiya, Y., Umezawa, S., Sakai, E. et al. Metformin for chemoprevention of metachronous colorectal adenoma or polyps in post-polypectomy patients without diabetes: a multicentre double-blind, placebo-controlled, randomised phase 3 trial. Lancet Oncol. 17, 475–483 (2016). (PMID: 10.1016/S1470-2045(15)00565-3) Jiralerspong, S., Palla, S. L., Giordano, S. H., Meric-Bernstam, F., Liedtke, C., Barnett, C. M. et al. Metformin and pathologic complete responses to neoadjuvant chemotherapy in diabetic patients with breast cancer. J. Clin. Oncol. 27, 3297–3302 (2009). (PMID: 10.1200/JCO.2009.19.6410) Liu, F., Yan, L., Wang, Z., Lu, Y., Chu, Y., Li, X. et al. Metformin therapy and risk of colorectal adenomas and colorectal cancer in type 2 diabetes mellitus patients: a systematic review and meta-analysis. Oncotarget 8, 16017–16026 (2017). (PMID: 10.18632/oncotarget.13762) Mc Menamin, Ú. C., Murray, L. J., Hughes, C. M. & Cardwell, C. R. Metformin use and survival after colorectal cancer: A population-based cohort study. Int. J. Cancer 138, 369–379 (2016). (PMID: 10.1002/ijc.29720) Meng, F., Song, L. & Wang, W. Metformin improves overall survival of colorectal cancer patients with diabetes: a meta-analysis. J. Diabetes Res. 2017, 5063239 (2017). (PMID: 10.1155/2017/5063239) Rocha, G. Z., Dias, M. M., Ropelle, E. R., Osório-Costa, F., Rossato, F. A., Vercesi, A. E. et al. Metformin amplifies chemotherapy-induced AMPK activation and antitumoral growth. Clin. Cancer Res. 17, 3993–4005 (2011). (PMID: 10.1158/1078-0432.CCR-10-2243) Miranda, V. C., Braghiroli. M. I., Faria, L. D., Bariani, G., Alex, A., Neto, J. E. B. et al. Phase 2 trial of metformin combined with 5-fluorouracil in patients with refractory metastatic colorectal cancer. Clin. Colorectal Cancer 15, 321–328 (2016). Parikh, A. B., Marrone, K. A., Becker, D. J., Brahmer, J. R., Ettinger, D. S. & Levy, B. P. A pooled analysis of two phase II trials evaluating metformin plus platinum-based chemotherapy in advanced non-small cell lung cancer. Cancer Treat. Res. Commun. 20, 100150 (2019). (PMID: 10.1016/j.ctarc.2019.100150) Eisenhauer, E. A., Therasse, P., Bogaerts, J., Schwartz, L. H., Sargent, D., Ford, R. et al. New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur. J. Cancer 45, 228–247 (2009). (PMID: 10.1016/j.ejca.2008.10.026) Fayers, P., Aaronson, N., Bjordal, K., Groenvold, M., Curran, D. & Bottomley, A. On behalf of the EORTC Quality of Life Group. EORTC QLQ-C30 Scoring Manual Guidelines for assessing quality of life in EORTC Clinical Trials. (2001). https://www.eortc.org/app/uploads/sites/2/2018/02/SCmanual.pdf . Simon, R. Optimal two-stage designs for phase II clinical trials. Control Clin. Trials 10, 1–10 (1989). (PMID: 10.1016/0197-2456(89)90015-9) Morales, D. R. & Morris, A. D. Metformin in cancer treatment and prevention. Annu. Rev. Med. 66, 17–29 (2015). (PMID: 10.1146/annurev-med-062613-093128) Daugan, M., Dufay Wojcicki, A., d’Hayer, B. & Boudy, V. Metformin: an anti-diabetic drug to fight cancer. Pharmacol. Res. 113(Pt A), 675–685 (2016). (PMID: 10.1016/j.phrs.2016.10.006) Souza, K. K. d. Irinotecano ativa a via PI3-quinase/AKT/mTOR em linhagem de adenocarcinoma de colon. (2007). http://repositorio.unicamp.br/jspui/handle/REPOSIP/309953 . Tonini, G., Imperatori, M., Vincenzi, B., Frezza, A. M. & Santini, D. Rechallenge therapy and treatment holiday: different strategies in management of metastatic colorectal cancer. J. Exp. Clin. Cancer Res. 32, 92 (2013). (PMID: 10.1186/1756-9966-32-92) Chibaudel, B., Tournigand, C., Bonnetain, F., Maindrault-Goebel, F., Lledo, G., André, T. et al. Platinum-sensitivity in metastatic colorectal cancer: towards a definition. Eur. J. Cancer 49, 3813–3820 (2013). (PMID: 10.1016/j.ejca.2013.07.150) Bhadkamkar, N. A., Sahin, I. H., Shen, Y., Hassabo, H. M., Kee, B. K., Hassan, M. et al. Outcomes in patients (pts) with colorectal cancer (CRC) treated with oxaliplatin-based chemotherapy (OC) following prior oxaliplatin exposure. J. Clin. Oncol. 31(4_suppl), 500 (2013). (PMID: 10.1200/jco.2013.31.4_suppl.500) Fukuoka, S., Hara, H., Takahashi, N., Kojima, T., Kawazoe, A., Asayama, M. et al. Regorafenib plus nivolumab in patients with advanced gastric or colorectal cancer: an open-label, dose-escalation, and dose-expansion phase Ib trial (REGONIVO, EPOC1603). J. Clin. Oncol. (2020). https://ascopubs.org/doi/10.1200/JCO.19.03296 . Iglesias, D. A., Yates, M. S., Van Der Hoeven, D., Rodkey, T. L., Zhang, Q., Burzawa, J. et al. Another surprise from Metformin: novel mechanism of action via K-Ras influences endometrial cancer response to therapy. Mol. Cancer Ther. 12, 2847–2856 (2013). (PMID: 10.1158/1535-7163.MCT-13-0439) Innocenti, F., Ou, F.-S., Qu, X., Zemla, T. J., Niedzwiecki, D., Tam, R. et al. Mutational analysis of patients with colorectal cancer in CALGB/SWOG 80405 identifies new roles of microsatellite instability and tumor mutational burden for patient outcome. J. Clin. Oncol. 37, 1217–1227 (2019). (PMID: 10.1200/JCO.18.01798) Trilla-Fuertes, L., Gámez-Pozo, A., Arevalillo, J. M., Díaz-Almirón, M., Prado-Vázquez, G., Zapater-Moros, A. et al. Molecular characterization of breast cancer cell response to metabolic drugs. Oncotarget 9, 9645 (2018). (PMID: 10.18632/oncotarget.24047) Shrestha, A., Martin, C., Burton, M., Walters, S., Collins, K. & Wyld, L. Quality of life versus length of life considerations in cancer patients: a systematic literature review. Psycho Oncol. 28, 1367–1380 (2019). (PMID: 10.1002/pon.5054) Cho, S. K., Hay, J. W. & Barzi, A. Cost-effectiveness analysis of regorafenib and TAS-102 in refractory metastatic colorectal cancer in the United States. Clin. Colorectal Cancer 17, e751–e761 (2018). (PMID: 10.1016/j.clcc.2018.08.003) Ren, L., Chen, L., Wu, W., Garribba, L., Tian, H., Liu, Z. et al. Potential biomarkers of DNA replication stress in cancer. Oncotarget 8, 36996–37008 (2017). (PMID: 10.18632/oncotarget.16940) |
المشرفين على المادة: | 7673326042 (Irinotecan) 9100L32L2N (Metformin) |
تواريخ الأحداث: | Date Created: 20210105 Date Completed: 20210927 Latest Revision: 20230127 |
رمز التحديث: | 20240628 |
مُعرف محوري في PubMed: | PMC7961008 |
DOI: | 10.1038/s41416-020-01208-6 |
PMID: | 33398062 |
قاعدة البيانات: | MEDLINE |
تدمد: | 1532-1827 |
---|---|
DOI: | 10.1038/s41416-020-01208-6 |