Skip to main content
SpringerLink
Log in

Pharmacokinetic Evaluation of Intrapleural Carboplatin in Patients with Malignant Pleural Effusion

  • Original Research Article
  • Published:
Drug Investigation Aims and scope Submit manuscript

Summary

Carboplatin 360 mg/m2 was administered intrapleurally to 4 patients with malignant pleural effusion. Simultaneous pleural fluid and plasma samples were collected at various times after treatment to measure the total and filterable levels of platinum. The pleural area under the concentration versus time curve (AUC) for filterable platinum was 26- to 98-fold greater than the corresponding plasma AUC, plasma levels remaining in the range of 3 to 18 μmol/L. The concentrations of platinum in plasma were compared with those observed in 7 additional patients receiving the same dose of carboplatin intravenously. The comparative intrapleural and intravenous therapy led to peak concentrations of platinum 6 to 7 times lower after intrapleural than after intravenous treatment, in significantly lower partial AUCs, and in prolonged levels of filterable platinum following intrapleural treatment. No significant difference, either for total or for filterable platinum, was noted comparing the overall plasma exposure. Systemic clearance and mean residence time values for filterable platinum in plasma were about 1.8 times lower and 2 times higher, respectively, after intrapleural treatment than after intravenous administration. Both the cumulative urinary excretion and renal clearance, as well as the apparent volume of distribution at steady-state for filterable platinum, were comparable with the values obtained after intravenous carboplatin. The observed differences in plasma pharmacokinetics between the 2 routes of administration mainly reflect the delayed absorption of carboplatin into the systemic circulation after intrapleural treatment. The locoregional treatment was well tolerated by all patients, and no symptoms of thoracic discomfort or acute toxicity were noted.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Rusch VW, Figlin R, Godwin D, et al. Intrapleural cisplatin and cytarabine in the management of malignant pleural effusions: a Lung Cancer Study Group trial. J Clin Oncol 1991; 9: 313–9

    PubMed  CAS  Google Scholar 

  2. Ruckdeschel JC, Moores D, Lee JY, et al. Intrapleural therapy for malignant pleural effusions. A randomized comparison of bleomycin and tetracycline. Chest 1991; 100: 1528–35

    Article  PubMed  CAS  Google Scholar 

  3. Markman M, Cleary S, Pfeifle CE, et al. Cisplatin administered by the intracavitary route as treatment for malignant mesothelioma. Cancer 1986; 58: 18–21

    Article  PubMed  CAS  Google Scholar 

  4. Bogliolo GV, Lerza L, Bottino GB, et al. Regional pharmaco-kinetic selectivity of intrapleural cisplatin. Eur J Cancer 1991; 7: 839–42

    Google Scholar 

  5. Markman M. Intraperitoneal antineoplastic agents for tumors principally confined to the peritoneal cavity. Cancer Treat Rev 1986; 13: 219–42

    Article  PubMed  CAS  Google Scholar 

  6. Dedrick RL, Myers CE, Bungay PM, et al. Pharmacokinetic rationale for peritoneal drug administration in the treatment of ovarian cancer. Cancer Treat Rep 1978; 62: 1–11

    PubMed  CAS  Google Scholar 

  7. Piver SM, Lele SB, Marchetti DL, et al. Intraperitoneal cisplatin, cytarabine and bleomycin after intravenous cisplatin-based chemotherapy in advanced ovarian adenocarcinoma. J Clin Oncol 1988; 6: 1679–84

    PubMed  CAS  Google Scholar 

  8. Howell SB, Zimm S, Markman M, et al. Long term survival of advanced refractory ovarian carcinoma patients with small volume-disease treated with intraperitoneal chemotherapy. J Clin Oncol 1987; 5: 1607–12

    PubMed  CAS  Google Scholar 

  9. Rusch VW, Niedzwiecki D, Tao Y, et al. Intrapleural cisplatin and mitomycin for malignant mesothelioma following pleurectomy: pharmacokinetic studies. J Clin Oncol 1992; 10: 1001–6

    PubMed  CAS  Google Scholar 

  10. Lerza R, Esposito M, Vannozzi M, et al. High doses of intrapleural cisplatin in a case of malignant pleural mesothelioma. Cancer 1994; 73: 79–84

    Article  PubMed  CAS  Google Scholar 

  11. Torsten U, Opri F, Weitzel H. Local therapy of malignant pleural effusion with mitoxantrone. Anticancer Drugs 1992; 3: 17–8

    Article  PubMed  CAS  Google Scholar 

  12. Adler RH, Sayek I. Treatment of malignant pleural effusion: a method using tube thoracostomy and talc. Ann Thorac Surg 1976; 22: 8–14

    Article  PubMed  CAS  Google Scholar 

  13. Ruckdeschel JC. Management of malignant pleural effusion: an overview. Semin Oncol 1988; 15 Suppl. B: 24–8

    PubMed  CAS  Google Scholar 

  14. Pfeifle CE, Howell SB, Markman M. Intracavitary cisplatin chemotherapy for mesothelioma. Cancer Treat Rep 1985; 69: 205–7

    PubMed  CAS  Google Scholar 

  15. Speyer JL, Beller U, Colombo N, et al. Intraperitoneal car-boplatin: favorable results in women with minimal residual ovarian cancer after cisplatin therapy. J Clin Oncol 1990; 8: 1335–41

    PubMed  CAS  Google Scholar 

  16. McVie JG, ten Bokkel Huinink WW, Dubbelman R, et al. Phase I study and pharmacokinetics of intraperitoneal carboplatin. Cancer Treat Rev 1985; 12 Suppl. A: 35–41

    Article  PubMed  Google Scholar 

  17. Elferink F, van der Vijgh WJF, Klein I, et al. Pharmacokinetics of carboplatin after intraperitoneal administration. Cancer Chemother Pharm 1988; 21: 57–60

    Article  CAS  Google Scholar 

  18. Howell SB, Pfeifle CE, Wung WE, et al. Intraperitoneal cisplatin with systemic thiosulfate protection. Ann Intern Med 1982; 97: 845–51

    PubMed  CAS  Google Scholar 

  19. DeGregorio MW, Lum BL, Holleran WM, et al. Preliminary observation of intraperitoneal carboplatin pharmacokinetics during a phase I study of the Northern California Oncology Group. Cancer Chemother Pharmacol 1986; 18: 235–8

    Article  PubMed  CAS  Google Scholar 

  20. Van der Vijgh WJF. Clinical pharmacokinetics of carboplatin. Clin Pharmacokinet 1991; 21: 242–61

    Article  PubMed  Google Scholar 

  21. Pera MF, Harder HC. Analysis for platinum in biological material by flameless atomic absorption spectrometry. Clin Chem 1977; 23: 1245–9

    PubMed  CAS  Google Scholar 

  22. Esposito M, Collecchi P, Oddone M, et al. Platinum assay by neutron activation analysis and atomic absorption spectros-copy in cisplatin treated pregnant mice. J Radioan Nucl Ch Ar 1987; 113: 437–43

    Article  CAS  Google Scholar 

  23. Gibaldi M, Perrier D, editors. Pharmacokinetics, 2nd ed. New York: Marcel Dekker, 1982

    Google Scholar 

  24. Harland SJ, Newell DR, Siddik ZH, et al. The pharmacokinetics of cis-diammine-1,1 -cyclobutane dicarbossilate platinum (II) (CBDCA) in patients with normal and impaired renal function. Cancer Res 1984; 44: 1693–7

    PubMed  CAS  Google Scholar 

  25. Elferink F, van der Vijgh WJF, Klein I, et al. Pharmacokinetics of carboplatin after IV administration. Cancer Treat Rep 1987; 71: 1231–7

    PubMed  CAS  Google Scholar 

  26. Van Echo DA, Egorin MJ, Whitacre MY, et al. Phase I clinical and pharmacologic trial of carboplatin daily for 5 days. Cancer Treat Rep 1984; 68: 1103–14

    PubMed  Google Scholar 

  27. Calvert AH, Newell DR, Gore ME. Future directions with carboplatin: can therapeutic monitoring, high-dose administration, and hematologic support with growth factors expand the spectrum compared with cisplatin?. Semin Oncol 1992; 1 Suppl. 2: 155–63

    Google Scholar 

  28. Los G, McVie JG. Experimental and clinical status of intraperitoneal chemotherapy. Eur J Cancer 1990; 26: 755–62

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Servizio di Farmacologia Tossicologica, Istituto Nazionale per la Ricerca sul Cancro, IST, Viale Benedetto XV, 10, 16132, Genova, Italy

    Mauro Esposito & Maria Vannozzi

  2. Clinica Medica R, Dipartimento Medicina Interna, University of Genoa, Genoa, Italy

    Roberto Lerza, Manlio Mencoboni, Giovan Battista Bottino, Giuseppe Bogliolo, Giorgio Castello, Alessandro Cerruti & Ivo Pannacciulli

  3. Centro di Informatica, Istituto Nazionale per la Ricerca sul Cancro, Genoa, Italy

    Luca Gogioso

Authors
  1. Mauro Esposito
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Roberto Lerza
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Maria Vannozzi
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Manlio Mencoboni
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Giovan Battista Bottino
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Giuseppe Bogliolo
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Luca Gogioso
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Giorgio Castello
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Alessandro Cerruti
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Ivo Pannacciulli
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Esposito, M., Lerza, R., Vannozzi, M. et al. Pharmacokinetic Evaluation of Intrapleural Carboplatin in Patients with Malignant Pleural Effusion. Drug Invest 8, 352–360 (1994). https://doi.org/10.1007/BF03257450

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF03257450

Keywords

Search

Navigation