A randomised, concentration-controlled, comparison of standard (5-day) vs. prolonged (15-day) infusions of etoposide phosphate in small-cell lung cancer

Joel, S., O'Byrne, Kenneth J., Penson, R., Papamichael, D., Higgins, A., Robertshaw, H., Rudd, R., Talbot, D., & Slevin, M. (1998) A randomised, concentration-controlled, comparison of standard (5-day) vs. prolonged (15-day) infusions of etoposide phosphate in small-cell lung cancer. Annals of Oncology, 9(11), pp. 1205-1211.

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Purpose: This randomised trial was designed to investigate the activity and toxicity of continuous infusion etoposide phosphate (EP), targeting a plasma etoposide concentration of either 3 μg/ml for five days (5d) or 1 μg/ml for 15 days (15d), in previously untreated SCLC patients with extensive disease. Patients and methods: EP was used as a single agent. Plasma etoposide concentration was monitored on days 2 and 4 in patients receiving 5d EP and on days 2, 5, 8 and 11 in patients receiving 15d EP, with infusion modification to ensure target concentrations were achieved. Treatment was repeated every 21 days for up to six cycles, with a 25% reduction in target concentration in patients with toxicity.

Results: The study has closed early after entry of 29 patients (14 with 5d EP, 15 with 15d EP). Objective responses were seen in seven of 12 (58%, confidence interval (CI): 27%-85%) evaluable patients after 5d EP, and two of 14 (14%, CI: 4%42%) evaluable patients after 15d EP (P = 0.038). Grade 3 or 4 neutropenia or leucopenia during the first cycle of treatment was observed in six of 12 patients after 5d EP and 0/14 patients after 15d EP (P = 0.004), with median nadir WBC count of 2.6 x 109/1 after 5d and 5.0 x 109/1 after 15d EP (P = 0.017). Only one of 49 cycles of 15d EP was associated with grade 3 or worse haematological toxicity, compared to 14 of 61 cycles of 5d EP.

Conclusions: Although the number of patients entered into this trial was small, the low activity seen at 1 μg/ml in the 15d arm suggests that this concentration is below the therapeutic window in this setting. Further concentration- controlled studies with prolonged EP infusions are required.

Impact and interest:

16 citations in Scopus
15 citations in Web of Science®
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ID Code: 65126
Item Type: Journal Article
Refereed: Yes
Additional Information: Articles free to read on journal website after 12 months
Additional URLs:
Keywords: Concentration-controlled, Etoposide, Randomised, Small-cell lung cancer, cyclophosphamide, doxorubicin, etopofos, vincristine, adult, aged, article, blood toxicity, clinical article, clinical trial, concentration response, controlled study, dose response, dose time effect relation, drug blood level, female, human, human cell, human tissue, intravenous drug administration, leukopenia, lung small cell cancer, male, neutropenia, priority journal, randomized controlled trial, Antineoplastic Agents, Carcinoma, Small Cell, Drug Administration Schedule, Humans, Lung Neoplasms, Middle Aged, Organophosphorus Compounds
DOI: 10.1023/A:1008437805286
ISSN: 0923-7534
Divisions: Current > Schools > School of Biomedical Sciences
Current > QUT Faculties and Divisions > Faculty of Health
Current > Institutes > Institute of Health and Biomedical Innovation
Copyright Owner: Copyright 1998 Oxford University Press
Deposited On: 05 Dec 2013 01:30
Last Modified: 27 Jan 2015 05:11

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