Skip to main content
Log in

Oral Alkylating Agents for Breast Cancer Therapy

  • Review Article
  • Published:
Drugs Aims and scope Submit manuscript

Abstract

Oral cyclophosphamide is well tolerated and effective. Published data support its use as part of adjuvant and metastatic breast cancer treatment regimens. Cyclophosphamide has generally been administered at a higher dose intensity when given orally compared with intravenous infusion. However, there is currently no evidence that oral cyclophosphamide is either more toxic or more or less effective than an equivalent dose of intravenous cyclophosphamide. There is evidence in both the adjuvant and metastatic settings that classical oral cyclophosphamide-methotrexate-fluorouracil (CMF) is more effective than intravenous CMF, possibly because of the greater dose intensity of classical CMF. Prolonged administration of oral cyclophosphamide up to high cumulative doses is associated with an elevated risk of a secondary leukaemia. The rates of chemotherapy-related amenorrhoea with oral cyclophosphamide are directly related to the total dose of cyclophosphamide administered and the patient’s age. With the growing availability of other oral cytotoxic agents with demonstrated effectiveness in breast cancer, it is likely that oral cyclophosphamide will be incorporated once again into regimens for both metastatic and adjuvant treatment.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. Tew KD, Colvin M, Chabner BA. Alkylating agents. In: Chabner BA, Longo DL, editors. Cancer chemotherapy and biotherapy. 2nd ed. Philadelphia: Lippincott-Raven, 1996: 297–332

    Google Scholar 

  2. Clamon GH. Alkylating agents. In: Perry MC, editor. The chemotherapy sourcebook. Baltimore: Williams & Wilkins, 1992: 286–300

    Google Scholar 

  3. Fisher B, Fisher ER, Redmond C. Ten-year results from the National Surgical Adjuvant Breast and Bowel Project (NSABP) clinical trial evaluating the use of L-phenylalanine mustard (L-PAM) in the management of primary breast cancer. J Clin Oncol 1986; 4: 929–41

    PubMed  CAS  Google Scholar 

  4. Rivkin SE, Green S, Metch B, et al. Adjuvant CMFVP versus melphalan for operable breast cancer with positive axillary nodes: 10-year results of a Southwest Oncology Group Study. J Clin Oncol 1989; 7: 1229–38

    PubMed  CAS  Google Scholar 

  5. Bonadonna G, Valagussa P, Rossi A, et al. Ten-year experience with CMF-based adjuvant chemotherapy in resectable breast cancer. Breast Cancer Res Treat 1985; 5: 95–115

    Article  PubMed  CAS  Google Scholar 

  6. Bonadonna G. Evolving concepts in the systemic adjuvant treatment of breast cancer. Cancer Res 1992; 52: 2127–37

    PubMed  CAS  Google Scholar 

  7. Fisher B, Brown AM, Dimitrov NV, et al. Two months of doxorubicin-cyclophosphamide with and without interval reinduction therapy compared with 6 months of cyclophos-phamide, methotrexate, and fluorouracil in positive-node breast cancer patients with tamoxifen-nonresponsive tumors: results from the National Surgical Adjuvant Breast and Bowel Project B-15. J Clin Oncol 1990; 8: 1483–96

    PubMed  CAS  Google Scholar 

  8. Hryniuk W, Levine MN. Analysis of dose intensity for adjuvant chemotherapy trials in stage II breast cancer. J Clin Oncol 1986; 4: 1162–70

    PubMed  CAS  Google Scholar 

  9. Bonadonna G, Valagussa P. Dose-response effect of adjuvant chemotherapy in breast cancer. N Engl J Med 1981;304: 10–5

    Article  PubMed  CAS  Google Scholar 

  10. Engelsman E, Klijn JCM, Rubens RD, et al. ‘Classical’ CMF versus a 3-weekly intravenous CMF schedule in post-menopausal patients with advanced breast cancer. An EORTC Breast Cancer Co-operative Group phase III trial (10808). Eur J Cancer 1991; 27: 966–70

    Article  PubMed  CAS  Google Scholar 

  11. Goldhirsch A, Coates AS, Colleoni M, et al. Adjuvant chemoendocrine therapy in postmenopausal breast cancer: cyclophosphamide, methotrexate, and fluorouracil dose and schedule may make a difference. International Breast Cancer Study Group. J Clin Oncol 1998; 16: 1358–62

    PubMed  CAS  Google Scholar 

  12. Kolaric K, Mechl Z. Combination of idarubicin and cyclophosphamide administered orally in untreated postmenopausal breast cancer patients. A phase II study. Oncology 1991; 48: 93–6

    CAS  Google Scholar 

  13. Fisher B, Rockette H, Fisher ER, et al. Leukemia in breast cancer patients following adjuvant chemotherapy or postoperative radiation: the NSABP experience. J Clin Oncol 1985; 3: 1640–58

    PubMed  CAS  Google Scholar 

  14. Curtis RE, Boice Jr JD, Stovall M, et al. Risk of leukemia after chemotherapy and radiation treatment for breast cancer. N Engl J Med 1992; 326: 1745–51

    Article  PubMed  CAS  Google Scholar 

  15. Cobleigh MA, Bines J, Harris D, et al. Amenorrhea following adjuvant chemotherapy for breast cancer. Proc Am Soc Clin Oncol 1995; 14: 158A

    Google Scholar 

  16. Goldhirsch A, Gelber RD, Castiglione M. The magnitude of endocrine effects of adjuvant chemotherapy for premenopausal breast cancer patients. Ann Oncol 1990; 1: 183–8

    PubMed  CAS  Google Scholar 

  17. Redwood WR, Colvin M. Transport of melphalan by sensitive and resistant L1210 cells. Cancer Res 1980; 40: 1144–9

    PubMed  CAS  Google Scholar 

  18. Ewig RAG, Kohn KW. DNA damage and repair in mouse leukemia L1210 cells treated with nitrogen mustard, 1,3-bis (2-chloroethyl)-l-nitrosourea, and other nitrosoureas. Cancer Res 1977; 37: 2114–22

    PubMed  CAS  Google Scholar 

  19. Teicher B A, Herman TS, Holden SA, et al. Tumor resistance to alkylating agents conferred by mechanisms operative only in vivo. Science 1990; 247: 1457–61

    Article  PubMed  CAS  Google Scholar 

  20. Schabel Jr FM, Trader MW, Laster Jr WR, et al. Patterns of resistance and therapeutic synergism among alkylating agents. Antibiot Chemother 1978; 23: 200–15

    PubMed  CAS  Google Scholar 

  21. Newlands ES, Blacklege GR, Slack JA, et al. Phase I trial of temozolomide (CCRG 81045; M & B 39831; NSC 362856). Br J Cancer 1992; 65A: 287–91

    Article  Google Scholar 

  22. Newlands ES, O’Reilly SM, Glaser MG, et al. The Charing Cross Hospital experience with temozolomide in patients with gliomas. Eur J Cancer 1996; 32A: 2236–41

    Article  PubMed  CAS  Google Scholar 

  23. Bleehen NM, Newlands ES, Lee SM, et al. Cancer Research Campaign phase II trial of temozolomide in metastatic melanoma. J Clin Oncol 1995; 12: 910–3

    Google Scholar 

  24. Raymond E, Izbicka E, Soda H, et al. Activity of temozolomide against human tumor colony-forming units. Clin Cancer Res 1997; 3: 1769–74

    PubMed  CAS  Google Scholar 

  25. MacDonald JR, Muscoplat CC, Dexter DL, et al. Preclinical antitumor activity of 6-hydroxymethyl acylfulvene, a semisynthetic derivative of the mushroom toxin illudin S. Cancer Res 1997; 57: 279–83

    PubMed  CAS  Google Scholar 

  26. Hoff PM, Lassere Y, Pazdur R. Tegafur/uracil plus calcium folinate in colorectal cancer: double modulation of fluorouracil. Drugs 1999; 58 Suppl. 3: 77–83

    Article  PubMed  CAS  Google Scholar 

  27. Diasio RB. Improving fluorouracil chemotherapy with novel orally administered fluoropyrimidines. Drugs 1999; 58 Suppl. 3: 119–26

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

O’Shaughnessy, J.A. Oral Alkylating Agents for Breast Cancer Therapy. Drugs 58 (Suppl 3), 1–9 (1999). https://doi.org/10.2165/00003495-199958003-00001

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.2165/00003495-199958003-00001

Keywords

Navigation