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Predictive performance of a pharmacodynamic model for oral etoposide.
Cancer Res. 1994 Apr 15; 54(8):2080-3.CR

Abstract

The objective of this work was to prospectively validate a pharmacodynamic model for 21-day oral etoposide. The model had been developed in 27 untreated patients with stage IIIB or IV non-small cell lung cancer. Treatment consisted of 50 mg/m2/day, p.o., etoposide for 21 days in combination with 100 mg/m2, i.v., cisplatin on day 1 every 28 days for up to 6 courses. Weekly evaluations included etoposide plasma concentrations (Ec, microgram/ml) before the daily dose and WBC and neutrophil counts (ANC, 10(3)/microliters). The relationship between Ec and the pretreatment (WBCp, ANCp) and nadir counts (WBCn, ANCn) in the first course was described as follows: WBCn = 0.35 (1 + WBCp x e-1.12 x Ec)) ANCn = 0.32 (1 + ANCp x e-2.47 x Ec) The same study criteria were used to enter 26 additional patients, and 21 were evaluable for pharmacodynamics (5 had incomplete data). Predicted nadir counts were not significantly different from observed nadir counts (paired t test, P > 0.4). There were 12 and 7 patients correctly predicted to be above and below, respectively, the clinically important ANCn of 0.5 x 10(3)/microliters. The model performed reliably, and therapeutic drug monitoring appears warranted in future studies.

Authors+Show Affiliations

Veterans Affairs Medical Center, Memphis, Tennessee.No affiliation info available

Pub Type(s)

Journal Article
Research Support, U.S. Gov't, Non-P.H.S.

Language

eng

PubMed ID

8174108

Citation

Miller, A A., and E A. Tolley. "Predictive Performance of a Pharmacodynamic Model for Oral Etoposide." Cancer Research, vol. 54, no. 8, 1994, pp. 2080-3.
Miller AA, Tolley EA. Predictive performance of a pharmacodynamic model for oral etoposide. Cancer Res. 1994;54(8):2080-3.
Miller, A. A., & Tolley, E. A. (1994). Predictive performance of a pharmacodynamic model for oral etoposide. Cancer Research, 54(8), 2080-3.
Miller AA, Tolley EA. Predictive Performance of a Pharmacodynamic Model for Oral Etoposide. Cancer Res. 1994 Apr 15;54(8):2080-3. PubMed PMID: 8174108.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Predictive performance of a pharmacodynamic model for oral etoposide. AU - Miller,A A, AU - Tolley,E A, PY - 1994/4/15/pubmed PY - 1994/4/15/medline PY - 1994/4/15/entrez SP - 2080 EP - 3 JF - Cancer research JO - Cancer Res. VL - 54 IS - 8 N2 - The objective of this work was to prospectively validate a pharmacodynamic model for 21-day oral etoposide. The model had been developed in 27 untreated patients with stage IIIB or IV non-small cell lung cancer. Treatment consisted of 50 mg/m2/day, p.o., etoposide for 21 days in combination with 100 mg/m2, i.v., cisplatin on day 1 every 28 days for up to 6 courses. Weekly evaluations included etoposide plasma concentrations (Ec, microgram/ml) before the daily dose and WBC and neutrophil counts (ANC, 10(3)/microliters). The relationship between Ec and the pretreatment (WBCp, ANCp) and nadir counts (WBCn, ANCn) in the first course was described as follows: WBCn = 0.35 (1 + WBCp x e-1.12 x Ec)) ANCn = 0.32 (1 + ANCp x e-2.47 x Ec) The same study criteria were used to enter 26 additional patients, and 21 were evaluable for pharmacodynamics (5 had incomplete data). Predicted nadir counts were not significantly different from observed nadir counts (paired t test, P > 0.4). There were 12 and 7 patients correctly predicted to be above and below, respectively, the clinically important ANCn of 0.5 x 10(3)/microliters. The model performed reliably, and therapeutic drug monitoring appears warranted in future studies. SN - 0008-5472 UR - https://www.unboundmedicine.com/medline/citation/8174108/Predictive_performance_of_a_pharmacodynamic_model_for_oral_etoposide_ L2 - http://cancerres.aacrjournals.org/cgi/pmidlookup?view=long&pmid=8174108 DB - PRIME DP - Unbound Medicine ER -