Dose Intensity Analysis May Help Resolve Issues in Chemotherapy with Platinum Compounds

  • W. Hryniuk


Attempts to define optimum chemotherapy in the clinical setting have resulted in a plethora of schedules and combinations. In addition various schemes are used to reduce doses and delay treatments in order to reduce toxicity. These schedules and schemes have obscured dose-response relationships which, however, can be rediscovered and studied by reducing all to how much drug is given per unit time, as mg/m2/wk regardless of the protocol schedule used. This is dose intensity (1). Dose intensity can be calculated from intended drug doses (“projected dose intensity”) or doses received after reductions and delays for toxicity (“received dose intensity”) and can be derived for single agent treatments as well as for combinations. In the calculation of dose intensity, treatment delays are assumed to be equivalent to dose reductions and are accorded equal weight arithmetically. Dose intensity correlates very well with outcome for a variety of single agents and drug combinations in various malignant diseases (2).


Ovarian Cancer Clin Oncol Dose Intensity Testicular Cancer Advance Ovarian Cancer 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    J.A. Green, A.A. Dawson, L.F. Fell, Measurement of drug dosage intensity in MVPP therapy in Hodgkins’s disease, Br J Clin Pharmacol 9:511–514,1980.PubMedCrossRefGoogle Scholar
  2. 2.
    W. Hryniuk, The Importance of Dose Intensity in Outcome of Chemotherapy In: Advances in Oncology, pp 121–141, Eds: Hellman S., Devita V., Rosenberg S., J.B. Lippincott Company, Philadelphia, PA.Google Scholar
  3. 3.
    F.A. Greco, C.G. Julian, R.L., Richardson, et al: Advanced Ovarian Cancer: Brief intensive combination chemotherapy in second-look operation, Obstet Gynecol 58:200–205, 1981.Google Scholar
  4. 4.
    W. Hryniuk, M.N. Levine: Analysis of dose intensity for adjuvant chemotherapy trials in stage II breast cancer. J Clin Oncol, 4:1162–1170, 1986.PubMedGoogle Scholar
  5. 5.
    E. Hernandez, M.B. Rosenhein, J. Villar, et al: Alternating multiagent chemotherapy for advanced ovarian cancer. J Surg Oncol, 22:87–91, 1983.PubMedCrossRefGoogle Scholar
  6. 6.
    L. Levin, W. Hryniuk: Dose intensity analysis of chemotherapy regimens in ovarian carcinoma. J Clin Oncol, 5:756–767, 1987.PubMedGoogle Scholar
  7. 7.
    L. Levin, W. Hryniuk, The Application of Dose Intensity to Problems in chemotherapy of Ovarian and Endometrial Cancer. Sem. in Onc. 14: 12–19, 1987.Google Scholar
  8. 8.
    R.F. Ozols, B.J. Corden, J. Jacob, et al.: High Dose Cisplatin in Hypertonie Saline, Ann Int Med 100:19–24, 1984.PubMedCrossRefGoogle Scholar
  9. 9.
    F. Levi, M. Benavides, C. Chevelle, et al: Chemotherapy of Advanced Ovarian Cancer With 4′-O-Tetrahydropyranyl Doxorubicin and Cisplatin: A Randomized Phase II Trial With an Evaluation of Circadian Timing and Dose-Intensity, J Clin Oncol 8:705–714, 1990.PubMedGoogle Scholar
  10. 10.
    D.R. Gandara, M.W. DeGregorio, H.J. Wold, B.J. Wilbur, M. Kohler, H.J. Lawrence, A.B. Deisseroth, and C.B. George: High-dose cisplatin in hypertonic saline: Reduced toxicity of a modified dose schedule and correlation with plasma pharmacokinetics. A Northern California Oncology Group (NCOG) pilot study in non-small cell lung cancer. J Clin Oncol, 4:1787–1793, 1986.PubMedGoogle Scholar
  11. 11.
    J.E. Mortimer, J. Chestnut, C.S. Higano, and G. Goodman, High Dose Cisplatin in Metastatic Melanoma: Comparison of Two Schedules, Proc Amer Soc Clin Oncol, 7:254, 1988.Google Scholar
  12. 12.
    N. Colombo, M.R. Pittelli, M. Marzola, A. Lissoni, L. Redaelli, & C. Mangioni., Randomized Study of Two Cisplatin (P) Dose-Intensity Regimens in Patients With Stage III/IV Epithelial Ovarian Cancer (EOC) Proc Amer Soc Clin Oncol, 9:160,1990.Google Scholar
  13. 13.
    C. Boni, G. Cocconi, R. Lottici, M. Bella, F. Leonardi, G. Ceci, R. Passalaequa, M. Melpignano, D. DeBiasi, C. Bordi, B. Biscottni, C. Finardi, Conventional vs High Dose-Intensity Cisplatin in Advanced Ovarian Cancer. Preliminary Report of a Randomized Trial, Proc Amer Soc Clin Oncol, 9:168, 1990.Google Scholar
  14. 14.
    J.K. Samson, S.E. Rivkin, S.E. Jones, et al: Dose-response and dose-survival advantage for high versus low-dose cisplatin combined with vinblastine and bleomycin in disseminated testicular cancer. A Southwest Oncology Group (SWOG) project, Cancer 53:1029–1035, 1984.PubMedCrossRefGoogle Scholar
  15. 15.
    C.R. Nichols, S.D. Williams, P.J. Loehrer, et al.: Randomized Study of Cisplatin Dose Intensity in Poor-Risk Germ Cell Tumors: A Southeastern Cancer Study Group and Southwest Oncology Group Protocol, J Clin Oncol, 9(7):1163–1172, 1991.PubMedGoogle Scholar
  16. 16.
    C. Mangioni, G. Bolis, S. Pecorelli, et al, Randomized Trial in Advanced Ovarian Cancer Comparing Cisplatin and Carboplatin, J Natl Cancer Inst, 81:1464–1471, 1989.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 1991

Authors and Affiliations

  • W. Hryniuk
    • 1
  1. 1.Hamilton Regional Cancer Centre and McMaster University HamiltonOntarioCanada

Personalised recommendations