Breast Disease pp 789-801 | Cite as

Systemic Treatment Drugs/Regimens and Dose Modifications

  • Naziye Ak
  • Adnan Aydiner


This chapter discusses chemotherapy regimens and targeted options for breast cancer treatment. Dose-limiting toxicities for targeted therapies are often markedly different from those of classic cytotoxic chemotherapy agents. This chapter briefly summarizes the recommendations for dose modifications of some new drugs.


Dose modification Everolimus Palbociclib Ribociclib Abemaciclib Olaparib Neratinib Lapatinib TDM-1 (Ado-trastuzumab Emtansine) Pertuzumab Trastuzumab 


  1. 1.
    Common Terminology Criteria for Adverse Events (CTCAE), Version 5.0, November 2017, National Institutes of Health, National Cancer Institute.Google Scholar
  2. 2.
    Yardley DA, Noguchi S, Pritchard KI, Burris HA, Baselga J, Gnant M, et al. Everolimus plus exemestane in postmenopausal patients with HR+ breast cancer: BOLERO-2 final progression-free survival analysis. Adv Ther. 30(10):870–84.CrossRefGoogle Scholar
  3. 3.
    Finn RS, Crown JP, Ettl J, Schmidt M, Bondarenko IM, Lang I, et al. Efficacy and safety of palbociclib in combination with letrozole as first-line treatment of ER-positive, HER2-negative, advanced breast cancer: expanded analyses of subgroups from the randomized pivotal trial PALOMA-1/TRIO-18. Breast Cancer Res. 2016;18(1):67. Scholar
  4. 4.
    Hortobagyi GN, Stemmer SM, Burris HA, Yap YS, Sonke GS, Paluch-Shimon S, et al. Updated results from MONALEESA-2, a phase III trial of first-line ribociclib plus letrozole versus placebo plus letrozole in hormone receptor-positive, HER2-negative advanced breast cancer. Ann Oncol. 2018;29(7):1541–7.
  5. 5.
    Goetz MP, Toi M, Campone M, Sohn J, Paluch-Shimon S, Huober J, et al. MONARCH 3: Abemaciclib as initial therapy for advanced breast Cancer. J Clin Oncol. 2017;35(32):3638–46. Epub 2017 Oct 2.CrossRefPubMedGoogle Scholar
  6. 6.
    Robson M, Im SA, Senkus E, Xu B, Domchek SM, Masuda N, et al. Olaparib for metastatic breast Cancer in patients with a germline BRCA mutation. N Engl J Med. 2017;377(6):523–33.CrossRefGoogle Scholar
  7. 7.
    Tiwari SR, Mishra P, Abraham J. Neratinib, a novel HER2-targeted tyrosine kinase inhibitor. Clin Breast Cancer. 2016;16(5):344–8.CrossRefGoogle Scholar
  8. 8.
    Chan A, Delaloge S, Holmes FA, Moy B, Iwata H, Harvey VJ, et al. Neratinib after trastuzumab-based adjuvant therapy in patients with HER2-positive breast cancer (ExteNET): a multicenter, randomized, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol. 2016;17(3):367–77.CrossRefGoogle Scholar
  9. 9.
    Cameron D, Casey M, Oliva C, Newstat B, Imwalle B, Geyer CE. Lapatinib plus Capecitabine in women with HER-2-positive advanced breast Cancer: final survival analysis of a phase III randomized TriaL. Oncologist. 2010;15(9):924–34.CrossRefGoogle Scholar
  10. 10.
    Bachelot T, Romieu G, Campone M, Diéras V, Cropet C, Dalenc F, et al. Lapatinib plus Capecitabine in patients with previously untreated brain metastases from HER2-positive metastatic breast Cancer (LANDSCAPE): a single-group phase 2 study. Lancet Oncol. 2013;14(1):64–71.CrossRefGoogle Scholar
  11. 11.
    Tykerb (lapatinib) [prescribing information]. East Hanover, NJ: Novartis Pharmaceuticals Corporation; 2017.Google Scholar
  12. 12.
    Child CGIII, Turcotte JG. Surgery and portal hypertension. In: Child CGIII, editor. The liver and portal hypertension. Philadelphia: WB Saunders; 1964. p. 50.Google Scholar
  13. 13.
    Isakoff SJ, Baselga J. Trastuzumab-DM1: building a chemotherapy-free road in the treatment of human epidermal growth factor receptor 2-positive breast cancer. J Clin Oncol. 2011;29(4):351–4. Epub 2010 Dec 20.CrossRefGoogle Scholar
  14. 14.
    Perez EA, Barrios C, Eiermann W, Toi M, Im YH, Conte P, Martin M, Pienkowski T, Pivot X, Burris H 3rd, Petersen JA, Stanzel S, Strasak A, Patre M, Ellis P. Trastuzumab emtansine with or without pertuzumab versus trastuzumab plus taxane for human epidermal growth factor receptor 2-positive, advanced breast cancer: primary results from the phase III MARIANNE Study. J Clin Oncol. 2017;35(2):141. Epub 2016 Nov 7.CrossRefGoogle Scholar
  15. 15.
    Guarneri V, Lenihan DJ, Valero V, Durand JB, Broglio K, Hess KR, et al. Long-term cardiac tolerability of trastuzumab in metastatic breast cancer: the M.D. Anderson Cancer Center experience. J Clin Oncol. 2006;24(25):4107–15.CrossRefGoogle Scholar
  16. 16.
    Mackey JR, Clemons M, Côté MA, Delgado D, Dent S, Paterson A, et al. Cardiac management during adjuvant trastuzumab therapy: recommendations of the Canadian Trastuzumab working group. Curr Oncol. 2008;15(1):24–35.CrossRefGoogle Scholar
  17. 17.
    Swain SM, Baselga J, Kim SB, Ro J, Semiglazov V, Campone M, et al. CLEOPATRA study group. Pertuzumab, trastuzumab, and docetaxel in HER2-positive metastatic breast cancer. N Engl J Med. 2015;372(8):724–34.CrossRefGoogle Scholar
  18. 18.
    Verma S, Miles D, Gianni L, Krop IE, Welslau M, Baselga J, et al. EMILIA study group. Trastuzumab emtansine for HER2-positive advanced breast cancer. N Engl J Med. 2012;367(19):1783–91.CrossRefGoogle Scholar

Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  • Naziye Ak
    • 1
  • Adnan Aydiner
    • 2
  1. 1.Department of Medical Oncology, Internal MedicineIstanbul University Istanbul Medical Faculty, Institute of OncologyIstanbulTurkey
  2. 2.Oncology Institute, Istanbul Medical FacultyIstanbul UniversityIstanbulTurkey

Personalised recommendations