Dosing strategies for anticancer drugs: the good, the bad and body-surface area

Felici, Alessandra; Verweij, Jaap; Sparreboom, Alex

doi:10.1016/s0959-8049(02)00151-x

Cited by 179 publications

(120 citation statements)

References 43 publications

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“…It could be hypothesized that differences in the dosage of an anticancer drug, such as for cytarabine in the different HOVON protocols will not necessarily affect the predictive power of MRD: a fixed dose of an anticancer agent due to differences in pharmacology and pharmacokinetics already results in actual differences among patients in drug concentrations at target. 20 The use of a higher dose, resulting in a large continuum of actual concentrations, result in a direct correlation with MRD, which is now independent of the dose used. Similarly, it is not even likely that different types of anticancer drugs would result in different types of MRD cells, for example, with such differences in clonogenic characteristics that would abrogate the relationship between MRD frequency and outgrowth characteristics.…”

Section: Discussionmentioning

confidence: 99%

MRD parameters using immunophenotypic detection methods are highly reliable in predicting survival in acute myeloid leukaemia

et al. 2004

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Outgrowth of minimal residual disease (MRD) in acute myeloid leukaemia (AML) is responsible for the occurrence of relapses. MRD can be quantified by immunophenotyping on a flow cytometer using the expression of leukaemia-associated phenotypes. MRD was monitored in follow-up samples taken from bone marrow (BM) of 72 patients after three different cycles of chemotherapy and from autologous peripheral blood stem cell (PBSC) products. The MRD% in BM after the first cycle (n ¼ 51), second cycle (n ¼ 52) and third cycle (n ¼ 30), as well as in PBSC products (n ¼ 39) strongly correlated with relapse-free survival. At a cutoff level of 1% after the first cycle and median cutoff levels of 0.14% after the second, 0.11% after the third cycle and 0.13% for PBSC products, the relative risk of relapse was a factor 6.1, 3.4, 7.2 and 5.7, respectively, higher for patients in the high MRD group. Also, absolute MRD cell number/ml was highly predictive of the clinical outcome. After the treatment has ended, an increase of MRD% predicted forthcoming relapses, with MRD assessment intervals of p3 months. In conclusion, MRD parameter assessment at different stages of disease is highly reliable in predicting survival and forthcoming relapses in AML. Leukemia (2004) IntroductionMinimal residual disease (MRD) cells, present in the bone marrow (BM) of patients with acute myeloid leukaemia (AML) after chemotherapy, are thought to be responsible for the emergence of a relapse. Monitoring of MRD cells by molecular biologic or immunophenotypic detection methods are thought to be of crucial value for defining individualized treatment of patients. Based on MRD frequencies patient-tailored postremission chemotherapy could be designed, which might reduce either the risk of relapse or, in case of withholding therapy to the patient, diminish morbidity and mortality. Also, when impending relapses can be predicted, these might be prevented by early therapeutic interventions. Furthermore, MRD frequency assessment can be used to quantify the leukaemia cell contamination of an autologous peripheral blood stem cell (PBSC) product in order to guide the decision of whether or not to purge, and in the latter case to establish the efficacy of leukaemia cell eradication.Immunophenotypic detection of MRD by flow cytometry can be performed by defining aberrant marker expressions, the socalled leukaemia-associated phenotypes (LAPs), on malignant cells at diagnosis. 1-6 These LAPs are not, or only in very low frequencies, present on normal blood or BM cells. This technique can be successfully applied in up to 80% of the AML patients in contrast to molecular biological techniques, which were until now applicable only in 20-30% of the cases. 7-9 So far, in AML the predictive value of MRD frequency detection using immunophenotyping has been reported by a few groups only. 6,[10][11][12] In adult AML patients, San Miguel et al 6,10 demonstrated the prognostic value of MRD after induction and intensification therapy, while Venditti et al 11 have found this after con...

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Section: Discussionmentioning

confidence: 99%

MRD parameters using immunophenotypic detection methods are highly reliable in predicting survival in acute myeloid leukaemia

et al. 2004

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“…It is also used to estimate surface area, which in turn can be used to calculate doses of certain drugs (Lack and Stuart-Taylor, 1997;Felici et al, 2002) and renal clearance (Jin et al, 2008). In intensive care units, it can be used to estimate tidal volumes of patients requiring artificial ventilation (The acute respiratory distress syndrome network, 2000) (lung volumes are predicted from height in each gender (Crapo et al, 1982a(Crapo et al, , 1982b).…”

Section: Introductionmentioning

confidence: 99%

Ulna length to predict height in English and Portuguese patient populations

et al. 2011

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Background/Objective: This study assessed the extent to which ulna length could be used to predict height and body mass index (BMI) in various groups of English and Portuguese hospitalised patients, and tidal volumes in critically ill patients at risk of requiring ventilatory support. Subjects/Methods: Bedside measurements of weight, height and ulna length were made in 507 patients (432 English, 75 Portuguese; 264 men, 243 women) with a mean age of 61.8 ± 18.9 years, height 165.1 ± 9.5 cm and BMI 26.7 ± 5.43 kg/m 2 . Results: Ulna length could be measured with ease in all subjects. The intra-observer technical error of measurement in the same subjects was 1%. Within each category of men and women aged o65 years and 65 years and over, there was no significant difference between the English and Portuguese in the intercept or regression coefficients for the ulna-height relationships. A strong relationship was found between predicted and measured height (r ¼ 0.963, standard error of the estimate 4.6 cm). The overall mean and s.d. of the difference was 0.3±2.7% of height, with no significant difference between English and Portuguese populations. The discrepancy between measured and predicted BMI corresponded to 0.7 ± 5.5% (s.d.) (all subjects) and for ventilatory volumes predicted from height (critically ill subjects only) 0.7±7.1%. Conclusion: Height can be predicted from ulna length with precision and ease in a wide range of patient groups, and without the need to use different equations in English and Portuguese populations. The predicted measurements are acceptable in most clinical circumstances.

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“…However, a comparison of the dosing regimens for these drugs demonstrates that instructions for dosing in infants and very young children frequently differ between tumour types and protocols without scientific rationale. Indeed, this is common with many other standard cytotoxic chemotherapeutic drugs used in paediatric oncology [5]. Dose may be based on body surface area in one disease and on weight in another for the same age infant or child or, alternatively, the dosage reduction for a younger child may be modified based on body size in one protocol and age in a similar study for a different tumour type.…”

Section: Introductionmentioning

confidence: 99%

Pharmacokinetics of carboplatin and etoposide in infant neuroblastoma patients

Veal

Cole

Errington

et al. 2009

Cancer Chemother Pharmacol

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Purpose Carboplatin and etoposide are commonly used chemotherapeutics for the treatment of many paediatric cancers. However, there are very limited published data concerning the pharmacokinetics of these agents in infants and very young children, for whom dose reductions are frequently implemented.Methods Etoposide (5 mg/kg; 2hr i.v. infusion) was co-administered with carboplatin (6.6 mg/kg; 1hr i.v. infusion) on each of 3 days of treatment and samples were taken between 0.5 and 4 hours after the start of administration, from a total of 19 neuroblastoma patients aged less than 1 year at diagnosis and weighing <12kg at treatment. Pharmacokinetic analysis was carried out using a non-linear mixed effects modelling (NONMEM) approach.Results Two compartment structural models were selected for both carboplatin and etoposide analysis. Body weight was strongly associated with carboplatin clearance, with a slightly weaker relationship observed with etoposide clearance. Carboplatin clearance values ranged from 12.8-33.6 ml/min, with total AUC values of 4.2-9.3 mg/ml.min achieved over the 3 days of treatment. Clearance values normalized to body weight were significantly higher in patients <12kg than in children >12kg, with mean ± SD values of 2.9 ± 0.4 and 2.5 ± 0.4 ml/min/kg respectively (P<0.05).Etoposide exhibited a median half-life of 4.6 hours (range: 4.1-6.6), a median AUC of 7.1 mg/ml.min (range: 3.4-11.0) and a median clearance of 6.6 ml/min (range: 3.2-13.0). ConclusionResults suggest that prediction of absolute carboplatin clearance values may be difficult in infant patients <12kg, with a small but significant difference in clearance values normalized to body weight observed in this patient group. Etoposide pharmacokinetic data support previous findings that question the utility of modified dosing in infants. The current study demonstrates the feasibility of generating informative pharmacokinetic data in infants and young children.

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Dosing strategies for anticancer drugs: the good, the bad and body-surface area

Cited by 179 publications

References 43 publications

MRD parameters using immunophenotypic detection methods are highly reliable in predicting survival in acute myeloid leukaemia

MRD parameters using immunophenotypic detection methods are highly reliable in predicting survival in acute myeloid leukaemia

Ulna length to predict height in English and Portuguese patient populations

Pharmacokinetics of carboplatin and etoposide in infant neuroblastoma patients

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