Independent thesis Advanced level (professional degree), 20 credits / 30 HE credits
A Covariate Analysis on the Integrated G-CSF-Myelosuppression Model –investigation of potential relationships between chemotherapy induced neutropenia, endogenous G-CSF and infection biomarkes
Angelica Quartino, Department of Pharmaceutical Biosciences,Division of Pharmacokinetics and Drug Therapy, 30 hp, Margareta Hammarlund-Udenaes
Introduction: Cancer patients have an increased risk of suffering from sever infections because the chemotherapy treatment often results in low levles of a certain type of white blood cell (neutrophils). The production of neutrophils is highly regulated by growth hormones (e.g. G-CSF) and the acute phase response to infections.
Aim: To identify patient factors that could explain the differences seen between patients and thus may be useful in individualizing the treatment to achieve maximum effect of the drugs without the patient suffering from life threatherning infections.
Materials and Methods: Population modelling and a significance level of p<0.01 was used to evaluate patient characteristics i.e. age, menopausal status (MP), infection markers i.e. interleukin-6 (IL6), α1-acidglycoprotein (AAG), c-reactive protein(CRP) and a severe condition called febrile neutropenia (FN). Data was avaliable from 49 breast cancer patients treated with chemotherapy. Due to long run times the model was also linearized (lin SCM).
Results: The following relations were found significant for neutrophils: baseline CRP and FN with baseline; age, MP, baseline IL6, AAG and CRP as well as FN, IL6 and CRP with the maturation time. For G-CSF, MP, baseline CRP, IL6 and AAG were related with baseline, change from baseline of CRP with the production and IL6 with the elimination. For the drug effect of epirucin and cyclophosphamide age, baseline CRP, IL6 and CRP were found.
Conclusions: Several patient characteristics were identified to explaind some of the variability seen between the patients. However the clinical relevance of these and the potential use for individualized therapy needs to be further explored.
2012. , 46 p.