Platinum and Other Metal Coordination Compounds in Cancer Chemotherapy

  • Stephen B. Howell

Table of contents

  1. Front Matter
    Pages i-xi
  2. Synthetic Chemistry and Biochemistry

    1. Stephen J. Lippard
      Pages 1-12
    2. Bernhard Lippert, Gudrun Frommer, Oliver Renn, Olga Krizanovic, Iris Dieter, Michael Krumm et al.
      Pages 25-35
    3. E. Segal-Bendirdjian, P. Brehin, B. Lambert, A. Laoui, J. Kozelka, J.-M. Garrot et al.
      Pages 37-49
    4. Geoffrey Wickham, Laurence Wakelin, Brian Palmer, Ho Lee, Paul Johnson, Bruce Baguley et al.
      Pages 51-60
    5. Trevor G. Appleton, John R. Hall, Paul D. Prenzler, Fraser B. Ross
      Pages 61-72
    6. Frederic Gaucheron, Marie-Agnes Lemaire, Jean Marc Malinge, Annie Schwartz, Marc Leng
      Pages 73-79
    7. Christen M. Giandomenico, Michael J. Abrams, Barry A. Murrer, Jean F. Vollano, Christopher F. J. Barnard, Kenneth R. Harrap et al.
      Pages 93-100
    8. Luigi Marzilli, S. Mukundan Jr., Yinghai Xu, Gerald Zon, Adelle Bergman, Paulos Yohannes et al.
      Pages 101-114
  3. Biochemical and Molecular Pharmacology

    1. Paul A. Andrews, Kathleen D. Albright
      Pages 151-159
    2. Hans H. Grunicke, Johann Hofmann, Karl Maly, Hermann Oberhuber, Florian Uberall, Alexander Egle et al.
      Pages 161-172
    3. Stephen B. Howell, Seiji Isonishi, Randolph C. Christen, Paul A. Andrews, Stephen C. Mann, Doreen Hom
      Pages 173-179
    4. N. P. Johnson, J. L. Butour, C. Cayrol, S. Cros, M. Defais, J. S. Hoffmann et al.
      Pages 181-193
    5. Alan Eastman, Michael Barry
      Pages 195-202
    6. Dominique Burnouf, Corinne Gauthier, Jean-Claude Chottard, Robert P. P. Fuchs
      Pages 203-212

About this book


Taken together the data presented in this review, and work by many other investigators, support the notion that DNA excision repair is important in a tumor cell's resistance to platinum compounds. Inhibition of this repair system by combination chemotherapy with the excision repair inhibitors HU and Ara-C produces synergistic cell kills and increased levels and persistance of DNA interstrand crosslinks. The studies with cis-DDP and ~-DDP in combination with UV­ induced thymine dimers suggest that there may be competition for DNA repair enzymes between the dimer and the platinum lesion. Whether the competing lesion is an intrastrand crosslink, interstrand crosslink, or platinum monoadduct (or all of these lesions) cannot be determined. The similarity between an intrastrand crosslink and a cyclobutane dimer suggests that these lesions may compete for repair. However, the increased peak levels of interstrand crosslinks, and increased persistence of these lesions at later time points suggest that this lesion may also be a substrate for the repair system. These observations may be of clinical relevance. Recently Dr. Kathy Albain of our institution has completed a Phase III I study using a 12 hour pretreatment with HU and Ara-C in patients prior to their cis-DDP therapy. She observed a significant number of responders in this trial (54). She is currently completing a second Phase IIII study substituting IV HU for the oral formulation. We anticipate initiating other clinical trials based upon these observations.


DNA biochemistry cancer treatment cell chemistry clinical trial enzymes ion transport pharmacology resistance toxicology tumor

Editors and affiliations

  • Stephen B. Howell
    • 1
  1. 1.University of California, San DiegoLa JollaUSA

Bibliographic information

  • DOI
  • Copyright Information Springer-Verlag US 1991
  • Publisher Name Springer, Boston, MA
  • eBook Packages Springer Book Archive
  • Print ISBN 978-1-4899-0740-0
  • Online ISBN 978-1-4899-0738-7
  • About this book