Melphalan in Isolated Limb Perfusion for Malignant Melanoma, Bolus or Divided Dose, Tissue Levels, the pH Effect

  • R. N. Scott
  • R. Blackie
  • D. J. Kerr
  • T. E. Wheldon
  • S. B. Kaye
  • R. M. MacKie
  • A. J. McKay

Abstract

Isolated limb perfusion (ILP) has now been practised for years [1], but many fundamental issues remain to resolved. This paper summarises three studies we have performed.

Keywords

Hydrolysis Toxicity HPLC Agar Lactate 

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References

  1. 1.
    Creech OJ, Krementz ET, Ryan RF, Winblad JN (1958) Chemotherapy of cancer: regional perfusion utilising an extracorporeal circuit. Ann Surg 148:616–632PubMedCrossRefGoogle Scholar
  2. 2.
    Chang SY, Alberts DS, Farquar D, Melnick LR, Walson PD, Salmon SE (1978) Hydrolysis and protein binding of melphalan. J Pharm Sci 67:682–684PubMedCrossRefGoogle Scholar
  3. 3.
    Hafstrom L, Hugander A, Jonsson P-E, Westling H, Ehrsson H (1984) Blood leakage and melphalan leakage from the perfusion circuit during regional hyperthermic perfusion for malignant melanoma. Cancer Treat Rep 68:867–872PubMedGoogle Scholar
  4. 4.
    Briele HA, Djuric M, Jung DT, Mortell T, Patel MK, Das Gupta TK (1985) Pharmacokinetics of melphalan in clinical isolation perfusion of the extremities. Cancer Res 45:1885–1889PubMedGoogle Scholar
  5. 5.
    Minor DR, Allen RE, Alberts D, Peng Y-M, Tardelli G, Hutchinson J (1985) A clinical and pharmacokinetic study of isolated limb perfusion with heat and melphalan for melanoma. Cancer 55:2638–2644PubMedCrossRefGoogle Scholar
  6. 6.
    Scott RN, Blackie R, Kerr DJ, Hughes J, Burnside G, MacKie RM, Kaye SB, McKay AJ (1987) Melphalan pharmacokinetics in isolated limb perfusion (ILP) for melanoma (abstract). ICRCT 87, Ulm, p G31Google Scholar
  7. 7.
    Benckhuijsen C, Kroom BBR, van Geel AN, Wieberdink J (1988) Regional perfusion treatment with melphalan for melanoma in a limb: an evaluation of drug kinetics. Eur J Surg Oncol 14:157–163PubMedGoogle Scholar
  8. 8.
    Osterheld HKO, Musch E, von Unruh GE, Loos U, Rauschecker H, Muhlenbruch BJ (1988) A sensitive high-performance liquid chromatographic assay for melphalan and its hydrolysis products in blood and plasma. Cancer Chemother Pharmacol 21:156–162PubMedCrossRefGoogle Scholar
  9. 9.
    Kroon BBR (1988) Regional isolation perfusion in melanoma of the limbs; accomplishments, unsolved problems, future. Eur J Surg Oncol 14:101–110PubMedGoogle Scholar
  10. 10.
    Furner RL, Brown RK (1980) L-Phenylalanine mustard (L-PAM): the first 25 years. Cancer Treat Rep 64:559–574PubMedGoogle Scholar
  11. 11.
    Scott RN, Wheldon TE, Kaye SB, MacKie RM, McKay AJ (1987) Multicellular tumour spheroids (MTS) as a model for thermochemotherapy with melphalan (abstract). ICRCT 87, Ulm, pA19Google Scholar
  12. 12.
    Yuhas JM, Li AP, Martinez AO, Ladman AJ (1977) A simplified method for production and growth of multicellular tumour spheroids. Cancer Res 37:3639–3643PubMedGoogle Scholar
  13. 13.
    Twentyman PR (1980) Response to chemotherapy of EMT6 spheroids as measured by growth delay and cell survival. Br J Cancer 42:297–304PubMedCrossRefGoogle Scholar
  14. 14.
    Parsons PG, Carter FB, Morrison L, Regius Mary Jr (1981) Mechanism of melphalan resistance developed in vitro in human melanoma cells. Cancer Res 41:1524–1534Google Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 1990

Authors and Affiliations

  • R. N. Scott
    • 1
  • R. Blackie
    • 1
  • D. J. Kerr
    • 1
  • T. E. Wheldon
    • 1
  • S. B. Kaye
    • 1
  • R. M. MacKie
    • 1
  • A. J. McKay
    • 1
  1. 1.Department of Vascular SurgeryGartnavel General HospitalGlasgowUK

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