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The Norton–Simon hypothesis: designing more effective and less toxic chemotherapeutic regimens

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  1. Norton L and Simon R (1976) Tumor size, sensitivity to therapy and the design of treatment protocols. Cancer Treat Rep 61: 1307–1317

    Google Scholar 

  2. Norton L and Simon R (1977) The growth curve of an experimental solid tumor following radiotherapy. J Natl Cancer Inst 58: 1735–1741

    Article  CAS  Google Scholar 

  3. Norton L and Simon R (1986) The Norton-Simon hypothesis revisited. Cancer Treat Rep 70: 163–169

    CAS  PubMed  Google Scholar 

  4. Skipper HE (1986) Laboratory models: some historical perspectives. Cancer Treat Rep 70: 3–7

    CAS  PubMed  Google Scholar 

  5. Norton L et al. (1976) Predicting the course of Gompertzian growth. Nature 264: 542–545

    Article  CAS  Google Scholar 

  6. Bonadonna G et al. (1995) Sequential or alternating doxorubicin and CMF regimens in breast cancer with more than three positive nodes. Ten-year results. JAMA 273: 542–547

    Article  CAS  Google Scholar 

  7. Bonadonna G et al. (2004) Clinical relevance of different sequencing of doxorubicin and cyclophosphamide, methotrexate and fluorouracil in operable breast cancer. J Clin Oncol 22: 1614–1620

    Article  CAS  Google Scholar 

  8. Goldie JH and Coldman AJ (1979) A mathematical model for relating the drug sensitivity of tumors to their spontaneous mutation rate. Cancer Treat Rep 63: 1727–1733

    CAS  PubMed  Google Scholar 

  9. Citron ML et al. (2003) Randomized trial of dose-dense versus conventionally scheduled and sequential versus concurrent combination chemotherapy as postoperative adjuvant treatment of node-positive primary breast cancer: first report of Intergroup trial C9741/Cancer and Leukemia Group B trial 9741. J Clin Oncol 21: 1431–1439

    Article  CAS  Google Scholar 

  10. Venturini M et al. (2005) Dose-dense adjuvant chemotherapy in early breast cancer patients: Results from a randomized trial. J Natl Cancer Inst 97: 1724–1733

    Article  CAS  Google Scholar 

  11. Norton L (2005) Conceptual and practical implications of breast tissue geometry: toward a more effective, less toxic therapy. Oncologist 10: 370–381

    Article  CAS  Google Scholar 

  12. Norton L et al. (2005) Optimizing chemotherapeutic dose-schedule by Norton-Simon modeling: capecitabine. In 96th Annual Meeting of the American Association of Cancer Research: 2005 April 16–20; Anaheim, abstract #5007

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Correspondence to Richard Simon.

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Simon, R., Norton, L. The Norton–Simon hypothesis: designing more effective and less toxic chemotherapeutic regimens. Nat Rev Clin Oncol 3, 406–407 (2006).

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