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Carboplatin and etoposide pharmacokinetics in patients with testicular teratoma

  • Original Articles
  • Carboplatin, Etoposid, Pharmacokinetics, Testicular Teratoma
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Summary

The pharmacokinetics of carboplatin and etoposide were studied in four testicular teratoma patients receiving four courses each of combination chemotherapy consisting of etoposide (120 mg/m2 daily×3), bleomycin (30 mg weekly) and carboplatin. The carboplatin dose was calculated so as to achieve a constant area under the plasma concentration vs time curve (AUC) of 4.5 mg carboplatin/ml x min by using the formula: dose=4.5×(GFR+25), where GFR is the absolute glomerular filtration rate measured by 51Cr-EDTA clearance. Carboplatin was given on either day 1 or day 2 of each course and pharmacokinetic studies were carried out in each patient on two courses. Etoposide pharmacokinetics were also studied on two separate courses in each patient on the day on which carboplatin was given and on a day when etoposide was given alone. The pharmacokinetics of carboplatin were the same on both the first and second courses, on which studies were carried out with overall mean ± SD values (n=8) of 4.8±0.6 mg/ml x min, 94±21 min, 129±21 min, 20.1±5.41, 155±33 ml/min and 102±24 ml/min for the AUC, beta-phase half-life (t1/2β), mean residence time (MRT), volume of distribution (Vd) and total body (TCLR) and renal clearances (RCLR), respectively. The renal clearance of carboplatin was not significantly different from the GFR (132±32 ml/min). Etoposide pharmacokinetics were also the same on the two courses studied, with overall mean values ±SD (n=8) of: AUC=5.1±0.9 mg/ml x min, t1/2α=40±9 min, t1/2β=257±21 min, MRT=292±25 min, Vd=13.3±1.31, TCLR=46±9 ml/min and RCLR=17.6±6.3 ml/min when the drug was given alone and AUC=5.3±0.6 mg/ml x min, t1/2α=34±6 min, t1/2β=242±25 min, MRT=292±25 min, Vd=12.5±1.81, TCLR=43±6 ml/min and RCLR=13.4±3.5 ml/min when it was given in combination with carboplatin. Thus, the equation used to determine the carboplatin accurately predicted the AUC observed and the pharmacokinetics of etoposide were not altered by concurrent carboplatin administration. The therapeutic efficacy and toxicity of the carboplatin-etoposidebleomycin combination will be compared to those of cisplatin, etoposide and bleomycin in a randomised trial.

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References

  1. Arbuck SG, Douglass HO, Crom WR, Goodwin P, Silk Y, Cooper C, Evans WE (1986) Etoposide pharmacokinetics in patients with normal and abnormal organ function. J Clin Oncol 4: 1690–1695

    Google Scholar 

  2. Calvert AH, Harland SJ, Newell DR, Siddik ZH, Jones AC, McElwain TJ, Raju S, Wiltshaw E, Smith IE, Baker JM, Peckham MJ, Harrap KR (1982) Early clinical studies with cis-diammine-1,1-cyclobutane dicarboxylate platitum II. Cancer Chemother Pharmacol 9: 140–147

    Google Scholar 

  3. Calvert AH, Newell DR, Gumbrell LA, Burnell M, O'Reilly S, Boxall FE, Gore ME, Wiltshaw E (1987) Carboplatin: prospectively guided dose-escalation in relation to renal function. Proc Am Soc Clin Oncol 6: 45

    Google Scholar 

  4. Chantler C, Garnett ES, Parsons V, Veall N (1969) Glomerular filtration rate measurement in man by the single injection methods using 51Cr EDTA. Clin Sci Mol Med 37: 169–180

    Google Scholar 

  5. Curt GA, Grygiel JJ, Corden BJ, Ozols RF, Weiss RB, Tell DT, Myers CE, Collins JM (1983) A phase I and pharmacokinetic study of diamminecyclobutane-dicarboxylatoplatinum (NSC 241240). Cancer Res 43: 4470–4473

    Google Scholar 

  6. D'Incalci M, Rossi C, Zucchetti M, Urso R, Cavalli F, Mangioni C, Willems Y, Sessa C (1986) Pharmacokinetics of etoposide in patients with abnormal renal and hepatic function. Cancer Res 46: 2566–2571

    Google Scholar 

  7. Egorin MJ, Van Echo DA, Tipping SJ, Olman EA, Whitacre MY, Thompson BW, Aisner J (1984) Pharmacokinetics and dosage reduction of cis-diammine-(1,1-cyclobutanedicarboxylato)platinum in patients with impaired renal function. Cancer Res 44: 5432–5438

    Google Scholar 

  8. Elferink F, van der Vijgh WJF, Klein I, Vermorken JB, Gall HE, Pinedo HM (1988) Pharmacokinetics of diammine(1,1-cyclobutanedicarboxylato)platinum(II)(carboplatin) after intravenous administration. Cancer Treat Rep 71: 1231–1237

    Google Scholar 

  9. Foster BJ, Clagett-Carr K, Leyland-Jones B, Hoth D (1985) Results of NCI-sponsored phase I trials with carboplatin. Cancer Treat Rev 12 [Suppl A]: 67–71

    Google Scholar 

  10. Gouyette A, Deniel A, Pico J-L, Droz J-P, Baume D, Ostronoff M, Le Bail N, Hayat M (1987) Clinical pharmacology of high-dose etoposide associated with cisplatin. Pharmacokinetic and metabolic studies. Eur J Cancer Clin Oncol 23: 1627–1632

    Google Scholar 

  11. Harland SJ, Newell DR, Siddik ZH, Chadwick R, Calvert AH, Harrap KR (1984) Pharmacokinetics of cis-diammine-1,1-cyclobutane dicarboxylate platinum (II) in patients with normal and impaired renal function. Cancer Res 44: 1693–1697

    Google Scholar 

  12. Harrap KR (1983) Platinum analogues: criteria for selection. In: Muggia FM (ed) Cancer chemotherapy I. Martinus Nijhoff, The Hague, pp 171–217

    Google Scholar 

  13. Houston JB (1985) Kinetics of drug metabolism and disposition: physiological determinants. In: Wilkinson GR, Rawlins DM (eds) Drug metabolism and disposition: considerations in clinical pharmacology. MTP Press, Lancaster, pp 63–90

    Google Scholar 

  14. Jennrich RI, Sampson PF (1968) Application of stepwise regression to nonlinear least squares estimation. Technometrics 10: 63–72

    Google Scholar 

  15. Koeller JM, Trump DL, Tutsch KD, Earhart RH, Davis TE, Tormey DC (1986) Phase I clinical trial and pharmacokinetics of carboplatin (NSC 241240) by single monthly 30-minute infusion. Cancer 57: 222–225

    Google Scholar 

  16. Loo JCK, Reigalman S (1970) Assessment of pharmacokinetic constants from postinfusion blood curves obtained after i.v. infusion. J Pharm Sci 59: 53–55

    Google Scholar 

  17. Newell DR, Siddik ZH, Gumbrell LA, Boxall FE, Gore ME, Smith IE, Calvert AH (1987) Plasma free platinum pharmacokinetics in patients treated with high dose carboplatin. Eur J Cancer Clin Oncol 23: 1399–1405

    Google Scholar 

  18. Ottaway JH (1973) Normalization in the fitting of data by iterative methods. Biochem J 134: 729–736

    Google Scholar 

  19. Ozols RF, Yagoda A (1987) Genitourinary cancer. In: Pinedo HM, Longo DL, Chabner BA (eds) Cancer chemotherapy and biological response modifiers, annual 9. Elsevier, Amsterdam, pp 280–302

    Google Scholar 

  20. Peckham MJ, Horwich A, Brada M, Drury A, Hendry WF (1985) cis-Diammine dicarboxylate platinum II (carboplatin) in the treatment of testicular germ-cell tumours: a preliminary report. Cancer Treat Rev 12 [Suppl A]: 101–110

    Google Scholar 

  21. Pfluger KH, Schmidt L, Mertel M, Jungclas H, Havemann K (1987) Drug monitoring of etoposide (VP16-213): correlation of pharmacokinetic parameters to clinical and biochemical data from patients receiving etoposide. Cancer Chemother Pharmacol 20: 59–66

    Google Scholar 

  22. Powis G (1982) Effect of human renal and hepatic disease on the pharmacokinetics of anticancer drugs. Cancer Treat Rev 9: 85–124

    Google Scholar 

  23. Reece PA, Bishop JF, Olver IN, Stafford I, Hillcoat BL, Morstyn G (1987) Pharmacokinetics of unchanged carboplatin in patients with small cell lung carcinoma. Cancer Chemother Pharmacol 19: 326–330

    Google Scholar 

  24. Sinkule JA, Hutson P, Hayes FA, Etcubanas E, Evans W (1984) Pharmacokinetics of etoposide in children and adolescents with refractory solid tumours. Cancer Res 44: 3109–3113

    Google Scholar 

  25. Thompson SW, Davis LE, Kornfield M, Hilgers RD, Standefer JC (1984) Cisplatin neuropathy: clinical, electrophysiological, morphologic and toxicologic studies. Cancer 54: 1269–1275

    Google Scholar 

  26. Van Echo DA, Egorin MJ, Whitacre MY, Olman EA, Aisner J (1984) Phase I and pharmacologic trial of carboplatin daily for 5 days. Cancer Treat Rep 68: 1103–1114

    Google Scholar 

  27. Van Glabbeke M, Renard J, Pinedo HM, Cavalli F, Vermorken J, Sessa C, Abele R, Clavel M, Monfardini S (1988) Iproplatin and carboplatin induced toxicities: overview of phase II clinical trial conducted by the EORTC early clinical trials co-operative group (ECTG). Eur J Cancer Clin Oncol 24: 255–262

    Google Scholar 

  28. Vogelzang NJ, Torkelson JL, Kennedy BJ (1985) Hypomagnesemia, renal dysfunction and Raynaud's phenomenon in patients treated with cisplatin, vinblastine and bleomycin. Cancer 56:2765–2770

    Google Scholar 

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Authors and Affiliations

  1. Drug Development Section, Institute of Cancer Research, Sutton, Surrey, UK

    David R. Newell, Lindsey A. Gumbrell, Francis E. Boxall & A. Hilary Calvert

  2. Section of Radiotherapy, Royal Marsden Hospital, Sutton, Surrey, UK

    Rosalind A. Eeles & Alan Horwich

Authors
  1. David R. Newell
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  2. Rosalind A. Eeles
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  3. Lindsey A. Gumbrell
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  4. Francis E. Boxall
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  5. Alan Horwich
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  6. A. Hilary Calvert
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Newell, D.R., Eeles, R.A., Gumbrell, L.A. et al. Carboplatin and etoposide pharmacokinetics in patients with testicular teratoma. Cancer Chemother. Pharmacol. 23, 367–372 (1989). https://doi.org/10.1007/BF00435838

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  • DOI: https://doi.org/10.1007/BF00435838

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