Results of a phase II clinical trial of 6-mercaptopurine (6MP) and methotrexate in patients with BRCA-defective tumours (2024)

References

  1. Ferlay, J. S. I, Ervik, M, Diksh*t, R, Eser, S, Mathers, C., Rebelo, M. et al. Rebelo M et al. GLOBOCAN2012 v1.0, Cancer Incidence and Mortality Worldwide: IARC CancerBase No. 11, Lyon, France: International Agency for Research on Cancer. http://globocan.iarc.fr (2013).

  2. Eisenhauer, E. A. Real-world evidence in the treatment of ovarian cancer. Ann. Oncol. 28, viii61–viii65 (2017).

    CAS PubMed Google Scholar

  3. Risch, H. A., McLaughlin, J. R., Cole, D. E., Rosen, B., Bradley, L., Kwan, E. et al. Prevalence and penetrance of germline BRCA1 and BRCA2 mutations in a population series of 649 women with ovarian cancer. Am. J. Hum. Genet. 68, 700–710 (2001).

    CAS PubMed PubMed Central Google Scholar

  4. Alsop, K., Fereday, S., Meldrum, C., deFazio, A., Emmanuel, C., George, J. 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. 30, 2654–2663 (2012).

    CAS PubMed PubMed Central Google Scholar

  5. McPherson, K., Steel, C. M. & Dixon, J. M. ABC of breast diseases. Breast cancer-epidemiology, risk factors, and genetics. BMJ. 321, 624–628 (2000).

    CAS PubMed PubMed Central Google Scholar

  6. Easton, D., Ford, D. & Peto, J. Inherited susceptibility to breast cancer. Cancer Surv. 18, 95–113 (1993).

    CAS PubMed Google Scholar

  7. Oesterreich, S. & Fuqua, S. A. Tumor suppressor genes in breast cancer. Endocr. Relat. Cancer. 6, 405–419 (1999).

    CAS PubMed Google Scholar

  8. Lakhani, S. R., Reis-Filho, J. S., Fulford, L., Penault-Llorca, F., van der Vijver, M., Parry, S. et al. Prediction of BRCA1 status in patients with breast cancer using estrogen receptor and basal phenotype. Clin. Cancer Res. 11, 5175–5180 (2005).

    CAS PubMed Google Scholar

  9. Bryant, H. E., Schultz, N., Thomas, H. D., Parker, K. M., Flower, D., Lopez, E. et al. Specific killing of BRCA2-deficient tumours with inhibitors of poly(ADP-ribose) polymerase. Nature 434, 913–917 (2005).

    CAS PubMed Google Scholar

  10. Farmer, H., McCabe, N., Lord, C. J., Tutt, A. N. J., Johnson, D. A., Richardson, T. B. et al. Targeting the DNA repair defect in BRCA mutant cells as a therapeutic strategy. Nature 434, 917–921 (2005).

    CAS PubMed Google Scholar

  11. Murai, J., Huang S-yN, Das, B. B., Renaud, A., Zhang, Y., Doroshow, J. H. et al. Trapping of PARP1 and PARP2 by Clinical PARP Inhibitors. Cancer Res. 72, 5588–5599 (2012).

    CAS PubMed PubMed Central Google Scholar

  12. Polak, P., Kim, J., Braunstein, L. Z., Karlic, R., Haradhavala, N. J., Tiao, G. et al. A mutational signature reveals alterations underlying deficient hom*ologous recombination repair in breast cancer. Nat. Genet. 49, 1476 (2017).

    CAS PubMed Google Scholar

  13. FDA. Lynparza (olaparib) tablets, for oral use: prescribing information. https://www.fda.gov/drugs/fda-approved-olaparib-lynparza-astrazeneca-pharmaceuticals-lp-maintenance-treatment-adult-patients (2018).

  14. Mirza, M. R., Monk, B. J., Herrstedt, J., Oza, A. M., Mahner, S., Redondo, A. et al. Niraparib maintenance therapy in platinum-sensitive, recurrent ovarian cancer. N. Engl. J. Med. 375, 2154–2164 (2016).

    CAS PubMed Google Scholar

  15. Coleman, R. L., Oza, A. M., Lorusso, D., Aghajanian, C., Oaknin, A., Dean, A. et al. Rucaparib maintenance treatment for recurrent ovarian carcinoma after response to platinum therapy (ARIEL3): a randomised, double-blind, placebo-controlled, phase 3 trial. The Lancet 390, 1949–1961 (2017).

    CAS Google Scholar

  16. Moore, K., Colombo, N., Scambia, G., Kim, B.-G., Oaknin, A., Friedlander, M. et al. Maintenance olaparib in patients with newly diagnosed advanced ovarian cancer. N. Engl. J. Med. 379, 2495–2505 (2018).

    CAS PubMed Google Scholar

  17. Robson, M., Im, S.-A., Senkus, E., Xu, B., Domchek, S. M., Masuda, N. et al. Olaparib for metastatic breast cancer in patients with a germline BRCA mutation. N. Engl. J. Med. 377, 523–533 (2017).

    CAS PubMed Google Scholar

  18. Barber, L. J., Sandhu, S., Chen, L., Campbell, J., Kozarewa, I., Fenwick, K. et al. Secondary mutations in BRCA2 associated with clinical resistance to a PARP inhibitor. J. Pathol. 229, 422–429 (2013).

    CAS PubMed Google Scholar

  19. Makvandi, M., Xu, K., Lieberman, B. P., Anderson, R.-C., Effron, S. S., Winters, H. D. et al. A radiotracer strategy to quantify PARP-1 expression in vivo provides a biomarker that can enable patient selection for PARP Inhibitor Therapy. Cancer Res. 76, 4516 (2016).

    CAS PubMed PubMed Central Google Scholar

  20. Ray Chaudhuri, A., Callen, E., Ding, X., Gogola, E., Duarte, A. A., Lee, J.-E. et al. Replication fork stability confers chemoresistance in BRCA-deficient cells. Nature 535, 382 (2016).

    PubMed Google Scholar

  21. Issaeva, N., Thomas, H. D., Djureinovic, T., Jaspers, J. E., Stoimenov, I., Kyle, S. et al. 6-thioguanine selectively kills BRCA2-defective tumors and overcomes PARP inhibitor resistance. Cancer Res. 70, 6268–6276 (2010).

    CAS PubMed PubMed Central Google Scholar

  22. Coulthard, S. & Hogarth, L. The thiopurines: An update. Investigational New Drugs. 23, 523–532 (2005).

    CAS PubMed Google Scholar

  23. Swann, P. F., Waters, T. R., Moulton, D. C., Xu, Y. Z., Zheng, Q., Edwards, M. et al. Role of postreplicative DNA mismatch repair in the cytotoxic action of thioguanine. Science 273, 1109–1111 (1996).

    CAS PubMed Google Scholar

  24. Griffin, S., Branch, P., Xu, Y. Z. & Karran, P. DNA mismatch binding and incision at modified guanine bases by extracts of mammalian cells: implications for tolerance to DNA methylation damage. Biochemistry 33, 4787–4793 (1994).

    CAS PubMed Google Scholar

  25. Waters, T. R. & Swann, P. F. Cytotoxic mechanism of 6-thioguanine: hMutSalpha, the human mismatch binding heterodimer, binds to DNA containing S6-methylthioguanine. Biochemistry. 36, 2501–2506 (1997).

    CAS PubMed Google Scholar

  26. Yan, T., Berry, S. E., Desai, A. B. & Kinsella, T. J. DNA mismatch repair (MMR) mediates 6-thioguanine genotoxicity by introducing single-strand breaks to signal a G2-M arrest in MMR-proficient RKO cells. Clin. Cancer Res. 9, 2327–2334 (2003).

    CAS PubMed Google Scholar

  27. Lennard, L. The clinical pharmacology of 6-mercaptopurine. Eur. J. Clin. Pharmacol. 43, 329–339 (1992).

    CAS PubMed Google Scholar

  28. Relling, M. V., Hanco*ck, M. L., Rivera, G. K., Sandlund, J. T., Ribeiro, R. C., Krynetski, E. Y. et al. Mercaptopurine therapy intolerance and heterozygosity at the thiopurine S-methyltransferase gene locus. J Natl Cancer Inst. 91, 2001–2008 (1999).

    CAS PubMed Google Scholar

  29. Dean L. Mercaptopurine Therapy and TPMT Genotype (eds Pratt V., McLeod H., Dean L., Malheiro A. & Rubinstein W.). (Medical Genetics Summaries, Bethesda, MD, 2012).

  30. Bokkerink, J. P., De Abreu, R. A., Bakker, M. A., Hulscher, T. W., van Baal, J. M., Schretlen, E. D. et al. Effects of methotrexate on purine and pyrimidine metabolism and cell-kinetic parameters in human malignant lymphoblasts of different lineages. Biochem. Pharmacol. 37, 2329–2338 (1988).

    CAS PubMed Google Scholar

  31. Martin, S. A., McCarthy, A., Barber, L. J., Burgess, D. J., Parry, S., Lord, C. J. et al. Methotrexate induces oxidative DNA damage and is selectively lethal to tumour cells with defects in the DNA mismatch repair gene MSH2. EMBO Mol. Med. 1, 323–337 (2009).

    CAS PubMed PubMed Central Google Scholar

  32. Nicum, S., Roberts, C., Boyle, L., Kopijasz, S., Gourley, C., Hall, M. et al. A phase II clinical trial of 6-mercaptopurine (6MP) and methotrexate in patients with BRCA defective tumours: a study protocol. BMC Cancer 14, 983 (2014).

    PubMed PubMed Central Google Scholar

  33. Jung, S. H., Carey, M. & Kim, K. M. Graphical search for two-stage designs for phase II clinical trials. Control Clin. Trials. 22, 367–372 (2001).

    CAS PubMed Google Scholar

  34. Jung, S. H., Lee, T., Kim, K. & George, S. L. Admissible two-stage designs for phase II cancer clinical trials. Stat Med. 23, 561–569 (2004).

    PubMed Google Scholar

  35. Hawwa, A. F., Millership, J. S., Collier, P. S. & McElnay, J. C. Development and validation of an HPLC method for the rapid and simultaneous determination of 6-mercaptopurine and four of its metabolites in plasma and red blood cells. J. Pharm. Biomed. Anal. 49, 401–409 (2009).

    CAS PubMed Google Scholar

  36. Kaufman, B., Shapira-Frommer, R., Schmutzler, R. K., Audeh, M. W., Friedlander, M., Balmana, J. et al. Olaparib monotherapy in patients with advanced cancer and a germline BRCA1/2 mutation. J. Clin. Oncol. 33, 244–250 (2015).

    CAS PubMed Google Scholar

  37. McNeish, I. A., Ledermann, J. A., Webber, L., James, L., Kaye, S. B., Hall, M. et al. A randomised, placebo-controlled trial of weekly pacl*taxel and saracatinib (AZD0530) in platinum-resistant ovarian, fallopian tube or primary peritoneal cancerdagger. Ann. Oncol. 25, 1988–1995 (2014).

    CAS PubMed Google Scholar

  38. Tan, D. S., Yap, T. A., Hutka, M., Roxburgh, P., Ang, J., Banerjee, S. et al. Implications of BRCA1 and BRCA2 mutations for the efficacy of pacl*taxel monotherapy in advanced ovarian cancer. Eu.r J. Cancer 49, 1246–1253 (2013).

    CAS Google Scholar

  39. Kaye, S. B., Lubinski, J., Matulonis, U., Ang, J. E., Gourley, C., Karlan, B. Y. et al. Phase II, open-label, randomized, multicenter study comparing the efficacy and safety of olaparib, a poly (ADP-ribose) polymerase inhibitor, and pegylated liposomal doxorubicin in patients with BRCA1 or BRCA2 mutations and recurrent ovarian cancer. J. Clin. Oncol. 30, 372–379 (2012).

    CAS PubMed Google Scholar

  40. Lilleyman, J. S. & Lennard, L. Mercaptopurine metabolism and risk of relapse in childhood lymphoblastic leukaemia. Lancet. 343, 1188–1190 (1994).

    CAS PubMed Google Scholar

  41. Hawwa, A. F., Collier, P. S., Millership, J. S., McCarthy, A., Dempsey, S., Cairns, C. et al. Population pharmaco*kinetic and pharmacogenetic analysis of 6-mercaptopurine in paediatric patients with acute lymphoblastic leukaemia. Br. J. Clin. Pharmacol. 66, 826–837 (2008).

    CAS PubMed PubMed Central Google Scholar

  42. Cheok, M. H. & Evans, W. E. Acute lymphoblastic leukaemia: a model for the pharmacogenomics of cancer therapy. Nat Rev Cancer. 6, 117–129 (2006).

    CAS PubMed Google Scholar

  43. Colombel, J. F., Ferrari, N., Debuysere, H., Marteau, P., Gendre, J. P., Bonaz, B. et al. Genotypic analysis of thiopurine S-methyltransferase in patients with Crohn’s disease and severe myelosuppression during azathioprine therapy. Gastroenterology. 118, 1025–1030 (2000).

    CAS PubMed Google Scholar

  44. Lennard, L., Welch, J. & Lilleyman, J. S. Mercaptopurine in childhood leukaemia: the effects of dose escalation on thioguanine nucleotide metabolites. Br. J. Clin. Pharmacol. 42, 525–527 (1996).

    CAS PubMed PubMed Central Google Scholar

  45. Dervieux, T., Brenner, T. L., Hon, Y. Y., Zhou, Y., Hanco*ck, M. L., Sandlund, J. T. et al. De novo purine synthesis inhibition and antileukemic effects of mercaptopurine alone or in combination with methotrexate in vivo. Blood. 100, 1240–1247 (2002).

    CAS PubMed Google Scholar

  46. McAlpine, J. N., Porter, H., Kobel, M., Nelson, B. H., Prentice, L. M., Kalloger, S. E. et al. BRCA1 and BRCA2 mutations correlate with TP53 abnormalities and presence of immune cell infiltrates in ovarian high-grade serous carcinoma. Mod. Pathol. 25, 740–750 (2012).

    CAS PubMed Google Scholar

  47. Strickland, K. C., Howitt, B. E., Shukla, S. A., Rodig, S., Ritterhouse, L. L., Liu, J. F. et al. Association and prognostic significance of BRCA1/2-mutation status with neoantigen load, number of tumor-infiltrating lymphocytes and expression of PD-1/PD-L1 in high grade serous ovarian cancer. Oncotarget 7, 13587–13598 (2016).

    PubMed PubMed Central Google Scholar

  48. Nolan, E., Savas, P., Policheni, A. N., Darcy, P. K., Vaillant, F., Mintoff, C. P., et al. Combined immune checkpoint blockade as a therapeutic strategy for BRCA1-mutated breast cancer. Sci. Transl. Med. 9, pii: eaal4922 (2017).

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Results of a phase II clinical trial of 6-mercaptopurine (6MP) and methotrexate in patients with BRCA-defective tumours (2024)

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