Abstract
The concept of dose-response is well established in the management of malignant disease. In some settings it has been shown that increasing dose intensity improves outcome (e.g., acute leukemia), but in most solid tumors optimal scheduling of drug delivery appears to be at least as important in defining outcome as the dose administered. In fact, several phase 3 randomized trials have failed to demonstrate a favorable impact on survival of “high-dose chemotherapy” in advanced/metastatic solid tumors. Considerable preclinical data support the relevance of the adequacy of drug delivery to the malignant cell population as being as important a factor in influencing the ultimate clinical outcome as the dose of drug administered. Examples of successful approaches to dose intensity in the management of malignant disease include intraperitoneal chemotherapy of ovarian cancer, and regional antineoplastic drug delivery in the treatment of superficial bladder cancer.
Keywords
- Epithelial Ovarian Cancer
- Antineoplastic Agent
- Tumor Cell Kill
- Antineoplastic Drug
- Superficial Bladder 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.
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Frei III E, Canellos GP. Dose: a critical factor in cancer chemotherapy. Am J Med. 1980;69:585–94.
Schabel Jr FM, Griswold Jr DP, Corbett TH, Laster Jr WR. Increasing therapeutic response rates to anticancer drugs by applying the basic principles of pharmacology. Pharmacol Ther. 1983;20:283–305.
Hennessy BT, Coleman RL, Markman M. Ovarian cancer. Lancet. 2009;374:1371–82.
Tan MC, Al MF, Gao F, et al. Predictors of complete pathological response after neoadjuvant systemic therapy for breast cancer. Am J Surg. 2009;198:520–5.
Kuhn W, Rutke S, Spathe K, et al. Neoadjuvant chemotherapy followed by tumor debulking prolongs survival for patients with poor prognosis in International Federation of Gynecology and Obstetrics Stage IIIC ovarian carcinoma. Cancer. 2001;92:2585–91.
Bessette AR, Benedetti-Panici PL, Boman K, et al. Randomised trial comparing primary debulking surgery (PDS) with neoadjuvant chemotherapy (NACT) followed by interval debulking (IDS) in stage IIIC-IV ovarian, fallopian tube and peritoneal cancer. IGCS 12th biennial meeting proceedings, Bangkok; 25–28 Oct 2008.
Hryniuk W, Levine MN. Analysis of dose intensity for adjuvant chemotherapy trials in stage II breast cancer. J Clin Oncol. 1986;4:1162–70.
Hryniuk W. Will increases in dose intensity improve outcome: pro. Am J Med. 1995;99:69S–70.
McGuire WP, Hoskins WJ, Brady MF, et al. Assessment of dose-intensive therapy in suboptimally debulked ovarian cancer: a Gynecologic Oncology Group study. J Clin Oncol. 1995;13:1589–99.
Gore M, Mainwaring P, A’Hern R, et al. Randomized trial of dose-intensity with single-agent carboplatin in patients with epithelial ovarian cancer. London Gynaecological Oncology Group. J Clin Oncol. 1998;16:2426–34.
Tallman MS, Gray R, Robert NJ, et al. Conventional adjuvant chemotherapy with or without high-dose chemotherapy and autologous stem-cell transplantation in high-risk breast cancer. N Engl J Med. 2003;349:17–26.
Grenman S, Wiklund T, Jalkanen J, et al. A randomised phase III study comparing high-dose chemotherapy to conventionally dosed chemotherapy for stage III ovarian cancer: the Finnish Ovarian Cancer (FINOVA) study. Eur J Cancer. 2006;42:2196–9.
Berry DA, Broadwater G, Klein JP, et al. High-dose versus standard chemotherapy in metastatic breast cancer: comparison of Cancer and Leukemia Group B trials with data from the Autologous Blood and Marrow Transplant Registry. J Clin Oncol. 2002;20:743–50.
Jodrell DI, Egorin MJ, Canetta RM, et al. Relationships between carboplatin exposure and tumor response and toxicity in patients with ovarian cancer. J Clin Oncol. 1992;10:520–8.
Markman M. Regional antineoplastic drug delivery in the management of malignant disease. Baltimore: The Johns Hopkins University Press; 1991.
Markman M, Walker JL. Intraperitoneal chemotherapy of ovarian cancer: a review, with a focus on practical aspects of treatment. J Clin Oncol. 2006;24:988–94.
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© 2011 Springer-Verlag Berlin Heidelberg
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Markman, M. (2011). The Principle of Dose-Response in Antineoplastic Drug Delivery. In: Aigner, K., Stephens, F. (eds) Induction Chemotherapy. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-18173-3_2
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DOI: https://doi.org/10.1007/978-3-642-18173-3_2
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