Predictive Drug Testing on Human Tumor Cells

1. Front Matter

   Pages I-XII

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2. Clonogenic Assays for Solid Tumors

   1. In Vitro Growth of Human Malignancies in a Cloning Assay

      • M. Rozencweig, V. Hofmann, C Sanders, W. Rombaut, U. Früh, G. Martz

      Pages 1-7

   2. Development and Applications of a Human Tumor Colony Assay for Chemosensitivity Testing

      • S. E. Salmon

      Pages 8-16

   3. A Replenishable Soft Agar Colony Assay for Human Tumour Sensitivity Testing

      • V. D. Courtenay

      Pages 17-34

   4. Analysis of Malignant Effusions by Cellular Composition, Proliferation Kinetics, and In Vitro Clonogenicity

      • V. Hofmann, M. E. Berens, U. Früh

      Pages 35-40

   5. Direct Cloning of Human Ovarian Cancer in Soft Agar: Clinical Limitations and Pharmacologic Applications

      • R. F. Ozols, W. M. Hogan, R. C. Young

      Pages 41-50

   6. Technical Problems with Soft Agar Colony Formation Assays for In Vitro Chemotherapy Sensitivity Testing of Human Solid Tumors: Mayo Clinic Experience

      • M. M. Lieber

      Pages 51-55

   7. Cloning of Human Tumor Cells in Methylcellulose-Containing Medium

      • C. Cillo, N. Odartchenko

      Pages 56-64

   8. The Effect of Chemotherapy on Human Bone Sarcomas: A Clinical and Experimental Study

      • H.-P. Honegger, A. von Hochstetter, P. Groscurth, V. Hofmann, M. Cserhati

      Pages 65-75

3. Predictive Tests for Hematological Malignancies

   1. Experimental Approaches to Outcome Prediction in Acute Myeloblastic Leukemia

      • E. A. McCulloch

      Pages 76-92

   2. Experimental Approaches to Drug Testing and Clonogenic Growth: Results in Multiple Myeloma and Acute Myelogenous Leukemia

      • B. G. M. Durie

      Pages 93-101

   3. In Vitro Assessment of Drug Sensitivity in Acute Nonlymphocytic Leukemia

      • H. D. Preisler, A. Raza

      Pages 102-115

   4. Short-Term In Vitro Sensitivity Testing in Acute Leukemia

      • J. D. Schwarzmeier, R. Pirker, E. Paietta

      Pages 116-126

4. Non-Clonogenic Assays for Drug Testing

   1. Development of a Nucleotide Precursor Incorporation Assay for Testing Drug Sensitivity of Human Tumors

      • O. Sanfilippo, M. G. Daidone, N. Zaffaroni, R. Silvestrini

      Pages 127-139

   2. Predictive Relevance for Clinical Outcome of In Vitro Sensitivity Evaluated Through Antimetabolic Assay

      • R. Silvestrini, O. Sanfilippo, M. G. Daidone, N. Zaffaroni

      Pages 140-150

   3. Biochemical Short-Term Predictive Assay: Results of Correlative Trials in Comparison to Other Assays

      • M. Kaufmann

      Pages 151-160

   4. In Vitro Chemosensitivity Assay Based on the Concept of Total Tumor Cell Kill

      • L. M. Weisenthal, R. H. Shoemaker, J. A. Marsden, P. L. Dill, J. A. Baker, E. M. Moran

      Pages 161-173

5. Evaluation of In Vitro Results

   1. Predictive Tests and Infrequent Events in Cancer Chemotherapy

      • M. Rozencweig, M. Staquet

      Pages 174-183

   2. Pharmacologic Pitfalls in the Human Tumor Clonogenic Assay

      • D. S. Alberts, J. Einspahr, R. Ludwig, S.E. Salmon

      Pages 184-190

   3. Heterogeneity and Variability of Test Results as Limiting Factors for Predictive Assays

      • P. Schlag, D. Flentje

      Pages 191-196

Predictive drug testing on human tumor cells in order to define the appropriate chemotherapy will remain imperative as long as the anticancer agents available are few in number and show only limited activity. The advantages of an effective test would lie in obviating the need for testing antineoplastic agents on large cohorts of patients for assessment of drug activity (phase II studies) and in allowing determination of optimal use of anticancer agents (phase III trials). Such an in vitro test could help to better define dose and schedule of drugs preclinically. The additive value of individual drugs could be determined on tumor cells in vitro in order to define the best combination chemotherapy in vivo. Test-directed therapy would avoid unnecessary drug-related morbidity in patients with refractory tumors. Chemotherapy treatment would be more than justified even with side effects if palliation or even prolonged survival could be anticipated as a result. The benefits of predictive drug testing on human tumor cells would extend beyond improvement of individual patient treatment if the testing helped to identify new active agents. This spectrum of benefits to the entire field of oncology pro­ vides tremendous motivation for the development of such testing. Although a number of chemosensitivity tests have been proposed since the advent of modern anticancer chemotherapy, interest has been renewed by the possibility of cloning human tumor cells on agar plates, with a view to testing drug activity on cells with high pro­ liferation capacity.

• Cells
• cancer
• chemotherapy
• drug
• morbidity
• tumor
• tumors

• Department für Innere Medizin, Abteilung für Onkologie, Universitätsspital Zürich, Zürich, Switzerland

  Victor Hofmann, Georg Martz

• Department of Obstetrics Gynecology, Bowman Gray, School of Medicine, Winston Salem, USA

  Michael E. Berens

Policies and ethics