The prospective randomized trial evaluating the efficacy of the mitomycin C and cisplatin regimen (MP) versus standard first-line chemotherapy in patients with advanced BRCA1/2-associated ovarian cancer (NCT04747717)
##article.numberofdownloads## 158
##article.numberofviews## 450
pdf (Русский)

Keywords

ovarian cancer
chemotherapy

How to Cite

Gorodnova, T., Sokolenko, A., Kotiv , K., Ivantsov, A., Yakovleva , M., Lavrinovich, O., Mikaya, N., Ibragimov, Z., Trifanov, Y., Bondarev , N., Smirnova, O., Guseinov, K., Bakhidze, E., Meshkova, I., Konstantinova, E., Urmancheeva, A., Berlev, I., Belyaev, A., & Imyanitov, E. (2022). The prospective randomized trial evaluating the efficacy of the mitomycin C and cisplatin regimen (MP) versus standard first-line chemotherapy in patients with advanced BRCA1/2-associated ovarian cancer (NCT04747717). Voprosy Onkologii, 68(5), 628–638. https://doi.org/10.37469/0507-3758-2022-68-5-628-638

Abstract

Introduction. BRCA1-associated ovarian cancer (OC) is characterized by high sensitivity to DNA-damaging agents, however, the most effective drug therapy regimen is not defined.

Aim. To compare the clinical efficacy of the combination «mitomycin C and cisplatin» (MP) and «paclitaxel and carboplatin» (TCbP) in neoadjuvant therapy of BRCA-associated ovarian cancer in the randomized trial.

Methods. The study involved 98 patients with advanced ovarian cancer, who were treated at N.N. Petrov NMRC of Oncology (St Petersburg, Russia) from 2019 to 2020. Sixteen carriers of pathogenic variants of BRCA1 and BRCA2 were identified. The patients were randomized at the ratio 1:1 into the experimental group for chemotherapy with the combination of mitomycin C and cisplatin (MP), or into the control group for standard chemotherapy with the combination of paclitaxel and carboplatin (TCbP)

Results. All 8 patients of the advanced BRCA-associated ovarian cancer demonstrated the objective clinical response to treatment in the MP group, whereas only 4 of 8 (50%) patients acieved the same in the TCbP group. Complete and moderate pathomorphologic response (CRS2 and CRS3) was observed in all women in the MP group and only in 5 of 8 (62.5%) patients in the TCbP group.

Twelve patients receiving MP regimen 22 patients who followed the TCbP regimen were included for long term outcomes assessment. Median recurrence-free survival in the MP group was significantly higher than in the TCbP group: 27.3 months versus 17.4 months (p=0.048).

Conclusions. The combination of mitomycin C and cisplatin is superior to the «gold standard» of neoadjuvant chemotherapy in patients with BRCA-associated OC.

https://doi.org/10.37469/0507-3758-2022-68-5-628-638
##article.numberofdownloads## 158
##article.numberofviews## 450
pdf (Русский)

References

Roy R, Chun J, Powell SN. BRCA1 and BRCA2: different roles in a common pathway of genome protection // Nat. Rev. Cancer. 2012;12(1):68–78.

Yoshida K, Miki Y. Role of BRCA1 and BRCA2 as regulators of DNA repair, transcription, and cell cycle in response to DNA damage // Cancer Sci. 2004;95(11):866–871.

Tan DSP, Kaye SB. Chemotherapy for Patients with BRCA1 and BRCA2–Mutated Ovarian Cancer: Same or Different? // Am. Soc. Clin. Oncol. Educ. B. 2015;35):114–121.

Fasano J, Muggia F. Breast cancer arising in a BRCA-mutated background: therapeutic implications from an animal model and drug development // Ann. Oncol. Off. J. Eur. Soc. Med. Oncol. 2009;20(4):609–614.

Martin LP, Hamilton TC, Schilder RJ. Platinum Resistance: The Role of DNA Repair Pathways // Clin. Cancer Res. 2008;14(5):1291–1295.

Siddik ZH. Cisplatin: mode of cytotoxic action and molecular basis of resistance // Oncogene. 2003;22(47):7265–7279.

Quinn JE et al. BRCA1 functions as a differential modulator of chemotherapy-induced apoptosis // Cancer Res. 2003;63(19):6221–6228.

Bolton KL et al. Association between BRCA1 and BRCA2 mutations and survival in women with invasive epithelial ovarian cancer // JAMA. NIH Public Access. 2012;307(4):382–390.

Tan DSP et al. Implications of BRCA1 and BRCA2 mutations for the efficacy of paclitaxel monotherapy in advanced ovarian cancer // Eur. J. Cancer. 2013;49(6):1246–1253.

Alsop K et al. BRCA Mutation Frequency and Patterns of Treatment Response in BRCA Mutation-Positive Women With Ovarian Cancer: A Report From the Australian Ovarian Cancer Study Group // J. Clin. Oncol. 2012;30(21):2654–2663.

Sun C et al. The role of BRCA status on the prognosis of patients with epithelial ovarian cancer: a systematic review of the literature with a meta-analysis // PLoS One/ed. Bishop A.J.R. 2014;9(5):e95285.

Yang D et al. Association of BRCA1 and BRCA2 Mutations With Survival, Chemotherapy Sensitivity, and Gene Mutator Phenotype in Patients With Ovarian Cancer // JAMA. 2011;306(14):1557.

Moynahan ME, Cui TY, Jasin M. Homology-directed dna repair, mitomycin-c resistance, and chromosome stability is restored with correction of a Brca1 mutation // Cancer Res. 2001;61(12):4842–4850.

Yun J et al. Hypersensitivity of Brca1-deficient MEF to the DNA interstrand crosslinking agent mitomycin C is associated with defect in homologous recombination repair and aberrant S-phase arrest // Oncogene. 2005;24(25):4009–4016.

van der Heijden MS BJR, Dezentje DA, Gallmeier E et al. In vivo Therapeutic Responses Contingent on Fanconi Anemia/BRCA2 Status of the Tumor // Clin. Cancer Res. 2005;11(20):7508–7515.

Santarosa M et al. Premature senescence is a major response to DNA cross-linking agents in BRCA1-defective cells: implication for tailored treatments of BRCA1 mutation carriers // Mol. Cancer Ther. 2009;8(4).

Gowen LC et al. BRCA1 required for transcription-coupled repair of oxidative DNA damage // Science. 1998;281(5379):1009–1012.

Bhattacharyya A et al. The breast cancer susceptibility gene BRCA1 is required for subnuclear assembly of Rad51 and survival following treatment with the DNA cross-linking agent cisplatin // J. Biol. Chem. American Society for Biochemistry and Molecular Biology. 2000;275(31):23899–23903.

Creech RH et al. Phase II study of low-dose mitomycin in patients with ovarian cancer previously treated with chemotherapy // Cancer Treat. Rep. 1985;69(11):1271–1273.

Shimizu Y, Umezawa S, Hasumi K. A phase II study of combined CPT-11 and mitomycin-C in platinum refractory clear cell and mucinous ovarian carcinoma // Ann. Acad. Med. Singapore. 1998;27(5):650–656.

Alberts DS, Garcia-Kendall D, Surwit EA. Phase II trial of mitomycin C plus 5-FU in the treatment of drug-refractory ovarian cancer // Semin. Oncol. 1988;15(3 Suppl 4):22–26.

Hempling RE et al. Lack of activity of 5-fluorouracil plus mitomycin-C as salvage therapy in cisplatin-resistant epithelial ovarian cancer: results of a phase II trial // Eur. J. Gynaecol. Oncol. 1994;15(3):165–169.

Massad LS et al. Salvage mitomycin/5-fluorouracil after platinum-based therapy for women with advanced ovarian cancer and related gynecologic malignancies // Eur. J. Gynaecol. Oncol. 1994;15(5):337–342.

Redman C et al. Phase II study of combination 4’-epidoxorubicin and mitomycin C in recurrent epithelial ovarian cancer // Cancer Chemother. Pharmacol. 1989;23(1):51–53.

Zhang J, Wang X, Lin C CFJ, Fei P. Altered expression of FANCL confers mitomycin C sensitivity in Calu-6 lung cancer cells // Cancer Biol. Ther. 2006;5(12):1632–1636.

Villalona-Calero MA et al. Veliparib Alone or in Combination with Mitomycin C in Patients with Solid Tumors With Functional Deficiency in Homologous Recombination Repair // J. Natl. Cancer Inst. Oxford University Press, 2016;108(7):djv437.

Городнова Т.В., Соколенко А.П., Иванцов А.О. и др. Системная терапия распространенного рака яичников у носительниц мутаций в гене BRCA1 ― новые лечебные подходы: результаты проспективного нерандомизированного многоцентрового исследования // Фарматека. 2018;7:57–64 [Gorodnova TV, Sokolenko AP, Ivancov AO et al. Systemic Therapy for Advanced Ovarian Cancer in Carriers of Mutations in the BRCA1 Gene ― New Treatment Approaches: Results of a Prospective Non-Randomized Multicenter Study // Farmateka. 2018;7:57–64 (In Russ.)].

Gorodnova TV et al. Efficacy of Neoadjuvant Therapy With Cisplatin Plus Mitomycin C in BRCA1-Mutated Ovarian Cancer // Int. J. Gynecol. Cancer. 2018;28(8):1498–1506.

Bohm S. Chemotherapy response score: development and validation of a system to quantify histopathologic response to neoadjuvant chemotherapy in tubo-ovarian high-grade serous carcinoma // J Clin Oncol. 2015;33:2457-2463.

Querleu D, Planchamp F, Chiva L et al. European Society of Gynaecological Oncology (ESGO) Guidelines for Ovarian Cancer Surgery/ /Int. J. Gynecol. Cancer. 2017;27:1534–1542.

Creative Commons License

This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.

© АННМО «Вопросы онкологии», Copyright (c) 2022