Effective chemotherapy support: a matter of timing and combining?
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RU Radboud Universiteit Nijmegen, 18 januari 2008
Promotores : Tjan-Heijnen, V.C., Mulder, P.H.M. de Co-promotor : Adang, E.M.M.
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SubjectUMCN 1.5: Interventional oncology
Unavoidably cytotoxic cancer therapy comes with side effects. Supportive care can alleviate chemotherapy-induced toxicity. Important complications of chemotherapy are neutropenia and its febrile complications (FN), which cause morbidity, lead to hospitalization, may compromise further treatment with chemotherapy in individual patients and at times can be fatal. With the introduction of filgrastim, caregivers were provided with a useful tool to prevent chemotherapy-induced neutropenia, but also with an economic burden as granulocyte-colony stimulating factor (G-CSF) is expensive. Therefore, effective use of G-CSF is essential. We demonstrated that the efficiency of support with daily G-CSF in dose-dense chemotherapy regimens can improve by timely withdrawal of G-CSF. The efficacy of G-CSF when used in combination with antibiotics was investigated. We demonstrated that with adequate support with the combination, a full dosed triplet is feasible, whereas without support complicated neutropenia indeed was the DLT at one third of the final dose of the third agent. In patients receiving standard dose chemotherapy and considered at risk of complicated neutropenia we demonstrated that the combination significantly reduced the incidence of FN when compared to antibiotics alone. A definite recommendation about whether to use or not to use the combination requires integration of clinical and economic data. The prospective cost-minimization analysis performed alongside the clinical trial of primary G-CSF and antibiotic prophylaxis in patients at risk of chemotherapy-induced FN demonstrated that the significant decrease in incidence of FN did not offset the additional costs of prophylactic G-CSF. By modeling cost-effectiveness of secondary prophylaxis we demonstrated that secondary prophylaxis with antibiotics is most favorable in monetary terms. The relatively high price of administering G-CSF is the determining factor. Finally an overview of the position of prophylaxis of FN is presented putting the results of the above mentioned studies into the perspective of relevant literature and the guidelines anno 2006.
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