Continuous-infusion verapamil with etoposide in relapsed or resistant paediatric cancers

Cowie, FJ, Pinkerton, CR, Phillips, M, Dick, G, Judson, I, McCarthy, PT and Flanagan, RJ (1995) Continuous-infusion verapamil with etoposide in relapsed or resistant paediatric cancers. British Journal of Cancer, 71 4: 877-881. doi:10.1038/bjc.1995.169


Author Cowie, FJ
Pinkerton, CR
Phillips, M
Dick, G
Judson, I
McCarthy, PT
Flanagan, RJ
Title Continuous-infusion verapamil with etoposide in relapsed or resistant paediatric cancers
Journal name British Journal of Cancer   Check publisher's open access policy
ISSN 1532-1827
Publication date 1995-01-01
Year available 1995
Sub-type Article (original research)
DOI 10.1038/bjc.1995.169
Open Access Status Not yet assessed
Volume 71
Issue 4
Start page 877
End page 881
Total pages 5
Publisher STOCKTON PRESS
Language eng
Subject 1306 Cancer Research
2730 Oncology
Abstract This study evaluates the use of a multidrug resistance (MDR) modulator (verapamil) in combination with a standard dose of single-agent etoposide in relapsed or refractory paediatric malignancy. A total of 20 patients (median age 6.5 years) were treated with an infusion of verapamil (loading dose 0.1 mg kg-1, followed by continuous infusion 0.15mg kg-1 h-1) for 72 h. Etoposide was given daily (150mg m-2 day-1) for three doses (each over 1 h); the first dose was given 12 h into the verapamil infusion. Cardiovascular toxicity was monitored by ECG and 2 hourly blood pressure and pulse recordings. Verapamil and norverapamil plasma concentrations were measured daily. Disease response was assessed after two courses. A total of 29/35 treatment courses were given at the desired verapamil dose; five courses required a dose reduction owing to cardiovascular toxicity. No patient required intensive monitoring. All patients who developed cardiovascular toxicity were over 14 years old. There was no correlation between plasma verapamil or norverapamil concentrations and toxicity. There were six partial responses (three rhabdomyosarcoma, three neuroblastoma) after two courses, but because of variation in the dose and schedule of etoposide these cannot be unequivocally contributed to MDR reversal. In conclusion, a regimen using a continuous infusion of verapamil combined with divided-dose etoposide is tolerable in children, and this strategy may be effective in refractory neuroblastoma and rhabdomyosarcoma.
Keyword Multidrug resistance
Paediatric cancer
Verapamil
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Unknown

Document type: Journal Article
Sub-type: Article (original research)
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