Pharmacokinetically guided dosing of carboplatin and etoposide during peritoneal dialysis and haemodialysis

English, Martin; Lowis, Stephen P.; Peng, Bo; Boddy, Alan V.; Newell, David R.; Price, L.; Pearson, Andrew D.J.

doi:10.1038/bjc.1996.135

Cited by 34 publications

(26 citation statements)

References 24 publications

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“…Quite contrary to cisplatin, the dialysability of etoposide was low in this study, while clearance of the agent in the haemodialysis patients was as efficient as that in patients with normal renal function. Although this observation is similar to previously published data (Holthuis et al, 1985;Sauer et al, 1990;Stewart, 1994), it seems at variance with the excretion routes of this drug in patients with normal renal function, where it is reportedly normally eliminated by renal (60%) and hepatic (40%) mechanisms (English et al, 1996). Our observation could be explained by the assumption that the hepatobiliary route completely compensates for the renal route in haemodialysis patients, but our study did not present any evidence to support this hypothesis.…”

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confidence: 34%

Feasibility of combination chemotherapy with cisplatin and etoposide for haemodialysis patients with lung cancer

et al. 2003

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Cancer chemotherapy for haemodialysis patients has never been established. To elucidate the feasibility of cisplatin-based combination chemotherapy for haemodialysis patients with lung cancer, a dose escalation study was conducted. Five haemodialysis patients with lung cancer were treated with cisplatin and etoposide. A starting dose of 40 mg m À2 of cisplatin on day 1 and 50 mg m À2 of etoposide on days 1, 3 and 5 were administered as the first course for the first patient. Membrane haemodialysis was regularly performed three times a week and soon after the completion of therapy. By monitoring toxicity and pharmacokinetics data, the dose was escalated course by course and patient by patient. Dose escalation was completed for the first two patients resulting in full-dose chemotherapy consisting of 80 mg m À2 of cisplatin on day 1 and 100 mg m À2 of etoposide on days 1, 3 and 5. Multiple courses of the full-dose chemotherapy were administered to the other three patients. Toxicity was manageable and tolerable for all. Pharmacokinetics data were comparable to those from patients with normal renal function, except for potential long-lasting higher levels of free platinum in the renal insufficiency group. In conclusion, this standard-dose combination chemotherapy was feasible even for haemodialysis patients.

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confidence: 34%

Feasibility of combination chemotherapy with cisplatin and etoposide for haemodialysis patients with lung cancer

et al. 2003

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“…Several concerns about this radical approach have been raised. The pharmacokinetics and pharmacodynamics of chemotherapy in anephric children on chronic dialysis have not been well studied, and the risk of infectious complications during chemotherapy in dialyzed children is increased as compared with patients maintaining renal functioning [16,19]. Therefore, some physicians advocate a more conservative approach in DDS patients with Wilms tumor and delay prophylactic nephrectomy until chemotherapy is completed.…”

Section: Discussionmentioning

confidence: 97%

Novel WT1 mutation (C388Y) in a female child with Denys-Drash syndrome

Swiatecka‐Urban

Mokrzycki

Kaskel

et al. 2001

Pediatric Nephrology

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We report the identification of a novel Wilms tumor suppressor gene mutation in a 5-month-old girl who presented with unilateral Wilms tumor (WT) and renal diffuse mesangial sclerosis typical of Denys-Drash syndrome (DDS). The patient did not have ambiguous genitalia and the karyotype (by amniocentesis) was 46, XX. A de novo constitutional heterozygous mutation in WT1 gene exon 9 coding for the third zinc-finger (1163G-->A, C388Y) was identified. This mutation affects a cysteine residue involved in the coordination of the zinc atom, confirming the importance of these residues in the biological function of WT1 protein.

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“…It seems likely that the reduced interpatient pharmacokinetic variability seen in this group of patients was due to the fact that only one child had previously received cisplatin, as cisplatin therapy has previously been shown to predict for reduced etoposide clearance (Pfluger et al, 1987(Pfluger et al, , 1993Relling et al, 1994 Previous studies involving targeted dosing with etoposide using limited sampling methods have involved the administration of etoposide as a continuous infusion over 3 or 5 days (Ratain et al, 1989(Ratain et al, , 1991Joel et al, 1996). In addition, English et al (1996) reported two anephric paediatric patients in whom targeted dosing with both etoposide and carboplatin was possible using detailed pharmacokinetic sampling over three doses. In this latter study, etoposide exposure was within 14% of the target in all four courses studied, despite etoposide plasma clearances varying between 14 and 23 ml min-' m-'.…”

Section: Discussionmentioning

confidence: 99%

A study of the feasibility and accuracy of pharmacokinetically guided etoposide dosing in children

Lowis

Price²,

Pearson³

et al. 1998

Br J Cancer

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Summary Pharmacokinetically guided dosing was performed in nine paediatric patients receiving etoposide. Doses on day 2 of a 2-or 3-day schedule were adapted on the basis of the day-1 area under the plasma etoposide concentration vs time curve (AUC). The day-1 AUC was estimated using a limited sampling model and the day-2 target AUC defined by the etoposide dose-AUC relationship observed in 33 children. Target AUC values (4.6-8.2 mg ml-1 x min) were achieved with a high degree of precision and with little bias (mean error 11% and root mean squared error 15% respectively). Pharmacokinetic parameters were similar to those reported previously in children, although interpatient pharmacokinetic variability was less than that observed previously: plasma clearance, 23 (18-26) ml min-' m-2; volume of distribution at steady state (Vdss), 6.0 (3.9-8.9) m-2; t,,2 254 (127-550) min (median and range). This study has demonstrated that pharmacokinetically guided dosing with etoposide is feasible. However, pharmacokinetically guided dosing is likely to be of most benefit in patients with abnormalities of renal or hepatic function, or in children with prior exposure to cisplatin.Keywords: etoposide; adaptive dosing; pharmacokinetics; children Etoposide is an active and widely used agent in paediatnic oncology.

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Pharmacokinetically guided dosing of carboplatin and etoposide during peritoneal dialysis and haemodialysis

Cited by 34 publications

References 24 publications

Feasibility of combination chemotherapy with cisplatin and etoposide for haemodialysis patients with lung cancer

Feasibility of combination chemotherapy with cisplatin and etoposide for haemodialysis patients with lung cancer

Novel WT1 mutation (C388Y) in a female child with Denys-Drash syndrome

A study of the feasibility and accuracy of pharmacokinetically guided etoposide dosing in children

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