R.lakesz H. Rainer (Eds.) Progress in Regional Cancer Therapy With 86 Figures and 111 Tables Springer-Verlag Berlin Heidelberg New York London Paris Tokyo HongKong Barcelona Professor Dr. Raimund Jakesz Allgemeines Krankenhaus der Stadt Wien 1. Chirurgische Universitiitsklinik Alser StraBe 4, 1090 Wien IX, Austria Professor Dr. Hugo Rainer Universitiitsklinik fur Chemotherapie Lazarettgasse 14, 1090 Wien IX, Austria ISBN-13: 978-3-642-74820-2 e-ISBN-13: 978-3-642-74818-9 DOl: 10.1007/978-3-642-74818-9 Library of Congress Cataloging-in-Publication Data Progress in regional cancer therapy /R. Jakesz, H. Rainer (eds.). p. cm. Based on a symposium held on Nov. 3-5, 1988 in Vienna. ISBN 0-387-51259-4 (U.S.:alk. paper) 1. Cancer-Treatment-Congresses. 2. Antineoplastic agents-Administration-Congresses. 3. Drug targeting-Congresses. I. Jakesz, R. (Raimund), 1950-. II. Rainer, H. (Hugo) [DNLM: 1. Antineoplastic Agents-administration & dosage-congresses. 2. Neoplasms-drug therapy-congresses. 3. Perfusion, Regional-congresses. QZ 267 P9637 1988] RC270.8.P75 1990 616.99'4061-dc20 DNLM/DLC 90-9521 This work is subject to copyright. All rights are reserved, whether the whole or part of the material is concerned, specifically the rights of translation, reprinting, reuse of illus trations, recitation, broadcasting, reproduction on microfilms or in other ways, and storage in data banks. Duplication of this publication or parts thereof is only permitted under the provisions of the German Copyright Law of September 9, 1965, in its current version, and a copyright fee must always be paid. Violations fall under the prosecution act of the German Copyright Law. . © Springer-Verlag Berlin Heidelberg 1990 Softcover reprint of the hardcover 1990 The use of registered names, trademarks, etc. in this publication does not imply, even in the absence of a specific statement, that such names are exempt from the relevant protective laws and regulations and therefore free for general use. Product Liability: The publisher can give no guarantee for information about drug dosage and application thereof contained in the book. In every individual case the respective user must check its accuracy by consulting other pharmaceutical literature. Typesetting: Thomson Press (India) Ltd., New Delhi 2125/3140-543210 - Printed on acid-free paper. Preface Systemic chemotherapy has long been used as a supplement to the surgical resection of primary tumors. Its relative lack of selectivity and its severe side effects prompted the search for more specific therapeutic modalities. The techniques using tumor-specific antigen-binding antibodies to carry substances which kill cancer cells and the approaches that take advantage of specific metabolic characteristics or of the presence of hormone receptors are examples of such therapies. Cancer therapy can also be made more specific by administering drugs directly to the target lesions via completely implantable, well tolerated systems. Knowledge of pharmacokinetics, meta bolism, drug distribution, and tolerance in defined anatomic regions is exploited to minimize the concentration of the anticancer agent in those parts of the body believed to be at lesser cancer risk. For most cytotoxics, the higher their concentration the greater their activity in tumor tissue. Selective administration increases the target: nontarged relation up to lOOO-fold. The symposium "Progress in Regional Cancer Therapy", held on November 3-5,1988 in Vienna, updated our knowledge of palliative and adjuvant therapies. It also showed us that much remains to be done in improving drug combinations, administration schedules and galenic forms for efficient treat ment in the different anatomic regions, as well as in selection of cancer types and stages for regional therapy. Although many questions are far from being answered, improvements in tumor remission rates, tolerance of treatment and quality of life will undoubtedly stimulate further research in this young area of chemotherapy. We hope that these edited proceedings of the Vienna meeting will be helpful in that pursuit. R. Jakesz H. Rainer Contents Advances in Drug Delivery ........................ . L. Domellof Advances in Drug Delivery to Cancer Patients: Introduction .................................... . C.l. van Groeningen Technical Developments in the Delivery of Antineoplastic Agents .... . . . . . . . . . . . . . . . . . . . . . . . 3 B. Gustavsson Is There a Pharmacologic Rationale for Continuous Cancer Chemotherapy? . . . . . . . . . . . . . . 5 L. Athlin, M. Hagberg, and Y. Wahlqvist Central Venous Access in Children Through a Fully Implantable Drug Delivery System. . . 10 V. Metzger and V. Laffer Intraportal Chemotherapy for Colorectal Hepatic Metastases. . . . . . . . . . . . . . . . . . . 16 Liver Metastases. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 25 H.H. Gruenagel, E. Mqlzahn, S. Neumann, and G.-V. Neukamp Prophylactic and Adjuvant Regional Chemotherapy of the Liver in Colorectal Malignancies. . . . . . . . . . . . . . 25 V. Laffer, V. Metzger, M. Arigoni, S. Arma, l. Barras, R. Egeli, S. Martinoli, W. Mueller, and W. Schweizer Randomized Multicenter Trial on Adjuvant Intraportal Chemotherapy for Colorectal Cancer (SAKK 40/81). . . 31 VIII Contents E. Petru, M.R. Berger, F. T. Garzon, and D. Schmahl Enhancement of Cytotoxic Efficacy of 5-Deoxy-5- fluorouridine in Acetoxymethyl-methylnitrosamine Induced Colorectal Adenocarcinomas in SD Rats by Locoregional Administration into the Inferior Mesenteric Artery. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 41 K.D. Griffith, A.E. Chang, and PH. Sugarbaker Second Hepatic Resections in Patients with Liver Metastases from Colorectal Carcinoma. . . . . 46 C. Hottenrott, M. Lorenz, R.P. Baum, M. Kirkowa-Reimann, T. Herrhausen, and R. Inglis Six Years of Experience with Local Chemotherapy of the Liver. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 52 J.A. Stephenson, A.L. Wiley, Jr., G. W. Wirtanen, and G. Ramirez Regional Therapy of Hepatic Metastases: Prognostic Factors. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 64 A. Schalhorn, G. Peyer/, W. Heinlein, and W. Wi/manns Regional Therapy with 5-Fluorouracil: Dependence of Systemic Concentrations on the Infusion Rate. . . . . . 70 F. Safi, R. Roscher, R. Bittner, K.H. Link, and H.G. Beger Combined Regional and Systemic Chemotherapy in Hepatic Metastases of Colorectal Carcinoma: Continuous IA Vs Simultaneous lA/IV FUDR Infusion. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 75 F. Sturba, R. Bencivenga, A. Paccapelo, L. Zepponi, M. Bonsignori, F. Mingolla, A. Cavicchi, F. Feliciotti, and S. Occhipinti Intra-arterial Chemotherapy of Liver Metastases. . . . . . 80 R. Bittner, F. Safi, K.H. Link, and H.G. Beger Current Standards and Limits in Treatment of Hepatic Metastases. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 83 L. Hakansson and H. Starkhammar Degradable Starch Microspheres in Intra-arterial Tumor Treatment: An Overview. . . . . . 89 T. Cooke and D. Chang Increasing the Uptake of a Low Molecular Weight Marker in Liver Tumours by Degradable Starch Micro- spheres: Possible Mechanisms of Action. . . . . . . . 98 M. Burk, W.D. Schoppe, A.A. Miller, R.M. Jungblut, and W. Schneider Dextrane Particle Use in Regional Chemotherapy: Problems of Monitoring. . . . . . . . . . . . . . . . . . . . . . . . . . .. 105 Contents IX M. Lorenz, C. Hottenrott, R.P. Bawn, D. Liermann, and A. Encke Chemoembolization of Hepatic Tumors with Degradable Starch Microspheres. . . . . . . . . . . . . . .. 110 Head and Neck Tumors. . . . . . . . . . . . . . . . . . . . . . . . . . . . 118 F. Scholz, K. Hollmann, J. KuhbOck, W. Dobrowsky, and R. Scholz Cytostatic Treatment of Advanced Squamous Cell Carcinoma of the Maxillofacial Region. . . . . . . . . . . . . . 118 H.P. H owaldt and K. Bitter A Complex Chemotherapeutic Concept in the Treatment of Oral Carcinomas with Cisplatin and 5-Fluorouracil. 124 A. Carbone, L. Bm'zan, R. Volpe, S. Sulfaro, G. Caruso, S. Frustaci, S. M onfardini, and R. Comoretto Pathological Assessment of the Results of Intra-arterial Chemotherapy for Head and Neck Carcinomas by Serial Sections of the Whole Specimen . . . . . . . . . . .. 131 J. von Scheel and E.R. Kastenbauer The Bypass Method in Head and Neck Cancer. . . . . .. 141 R. Pavelka, K. Hollmann, F. Scholz, and C. Schober Intratumoral Treatment of Incurable Head and Neck Cancer with Recombinant Human Tumor Necrosis Factor-IX. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 145 K.G. Vinzenz, N. Neuhold, H. Porteder, M. Matejka, G. Watzek, and M. Micksche Preoperative Local Immunotherapy with OK-432 (Picibanil) in Patients with Squamous Cell Cancer of the Oral Cavity. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 149 Extremity Tumors. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 155 H.J. Hoekstra, H. Schraffordt Koops, J. Oldhoff, W.M. Molenaar, D.TSleijfer, and D.M. Mehta Intra-arterial Chemotherapy, Preoperative and Postoperative Radiotherapy, and Surgery for Primary "Unresectable" High-Grade Soft Tissue Sarcomas of the Extremities .............................. . .. 155 F.O. Stephens, W. Marsden, and M.H.N. Tattersall Regional Induction Chemotherapy Followed by Radio therapy and/or Surgery in Management of Large and Aggressive Sarcomas in Shoulder, Pelvis and Limbs. .. 160 X Contents G. Bacci. P. Picci. M. Mercuri. M. Avella. M. Fontana. A. Mancini. F. Gherlinzoni. A. Brach del Prever. A. Ferraro. A. Ferruzzi. P. Caldora. and M. Campanacci Neo-adjuvant Chemotherapy for Osteosarcoma of the Extremities: The Experience at the Rizzoli Institute in 210 Patients Treated with Two Successively Activated Preoperative Protocols Using High-Dose or Moderate-Dose Methotrexate + Cisplatin or High-Dose Methotrexate + Cisplatin + Doxorubicin 168 F.R Eilber. J.F. Huth. G. Rosen. and M. Selch Neo-adjuvant Therapy of Soft Tissue Sarcomas of the Extremities with Intra-arterial Chemotherapy and Radiation. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 175 Melanoma ........ _. . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 182 W Hohenberger Isolation Perfusion for Malignant Melanomas: Established Facts and Parameters to Be Clarified. . . .. 182 C. Gross. R Mair. and P. Briicke Regional Extremity Perfusion in Patients with Malignant Melanoma. . . . . . . . . . . . . . . . . . . . . . . .. 188 B.B.R. Kroon. A.N. van Geel. H.R. Franklin. J.M. Klaase. and C. Benckhuijsen Preliminary Results of a Double Perfusion Schedule with Melphalan in Measurable Melanoma. .. .. .. . . . .. 192 RN. Scott. R Blackie. D.J. Kerr. T.E. Wheldon. S.B. Kaye. RM. MacKie. and A.J. McKay Melphalan in Isolated Limb Perfusion for Malignant Melanoma, Bolus for Divided Dose, Tissue Levels, the pH Effect. . . . . . . . . . . . . . . . . . . . . . .. 195 W Hohenberger. J. Gohl. and C. Kessler Isolation Perfusion of Malignant Soft Tissue Tumors.. 201 Intravesical Therapy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 204 K. Burk. W Schultze-Seemann. and G. Rodeck The Effect of Topical Adriamycin in Superficial Bladder Tumors: A 5-Year Follow-up. ... 204 H. Leyh Topical Instillation of Mitomycin C in the Treatment of Superficial Bladder Tumors: Long-Term Observation. . . . . . . . . . . . . . . . . . . . . . . . . . .. 208 Contents XI U. Maier and G. Baumgartner Mitomycin and Hyaluronidase in the Prevention of Recurrent Bladder Tumor. . . . . . . . . . . . . . . . . . . . . . .. 212 R. Hasun, W. Holtl, W. Albrecht, and M. Marberger How Effective is Topical Interferon-a2b for Preventing Recurrence of Superficial Bladder Cancer. . . . . . . . . . . .. 216 M. Bonsignori, F. Sturba, A. Paccapelo, R. Bencivenga, L. Zepponi, M. Polito, G. Muzzonigro, D. Minardi, L. Graziani, R. Montironi, and L. Possati Neo-adjuvant Intra-arterial Chemotherapy for Treatment of Locally Advanced Bladder Cancer: Therapeutic Protocol and Preliminary Report. . . . . . . .. 218 Radiotherapy. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 221 H. Kiircher and K.-H. Kiircher Reconstructive Microsurgery and Radiotherapy in Advanced Tumors of the Head and Neck. . . . . . . . .. 221 P. Kohek, B. Pakisch, F.-M. Smolle-Juttner, P. Rehak, G. Stuckelschweiger, and G. Friehs Palliation of Nonresectable Esophageal Cancer by Irridium-192 Intraluminal Afterloading ............ 226 G. Reiner, W. Seitz, A.P. Schmid, R. Jakesz, R. Kolb, M. Sperlich, A. Reiner, and J. Spona Interstitial Radiotherapy with Iridium-192 in the Treatment of Early Breast Cancer . . . . . . . . . . . .. 232 K. Koch, J. Frohwein, W. Bergemann, F. Gramlich, P. Semler, and M. Zschiederich Intracavitary High-Dose-Rate Afterloading Irradiation in the Treatment of Cancer of the Esophagus and Gastroesophageal Junction. . . .. 238 H.D. Kogelnik External Radiotherapy for Local and Regional Control of Lung Cancer. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 241 Hyperthermia. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 247 G. Cruciani, V. Salerno, E. Crippa, M. Morelli, G. Gnani, and M. Marangolo Clinical Experience with a Multifrequency Hyper thermia System and Chemotherapy in the Treatment of Superficial Metastases. . . . . . . . . . .. 247 XII Contents P. Steindorfer, R. Germann, A. Berger, G. Wolf, H.J. Mischinger, S. Uranus, P. Rehak, K. Arian-Schad, and M. Klimpfinger Recent Clinical Experience with an Annular Phased Array Hyperthermia System in the Treatment of Advanced Recurrences in the Pelvis. . . . . . . . . . . . . .. 252 L. Handl-Zeller, K. Schreier, K.H. Karcher, M. Budihna, and H. Lesnicar The Viennese Interstitial System KHS 9/W 18: Homogenous Hyperthermia with Simultaneous Radiation in Deep-seated Tumors with Integrated Heat Protection of Normal Tissue. . . .. 257 H.J. Feldmann, M. Molls, S. Adler, and H. Sack Thermoradiotherapy of Superficial and Half-Deep-seated Tumors: Thermal Profiles and Tumor Response. . . . . . . . . . . . . .. 260 H. Foth, H. Rauschecker, C. Willen brock, H.C. Michaelis, F. Horst, E. Voth, E. Musch, U. Laos, and G.F. Kahl Comparison of Leakage Measurement Using 99mTc-Labeled Red Blood Cells and Peripheral Melphalan Determination in Hyperthermic Isolation Perfusion of the Extremities. 266 H.J. Hoekstra, WM. Molenaar, H. SchrajJordt Koops, and J. OldhojJ Clinical and Histopathological Aspects of Hyperthermic Isolated Regional Perfusion of Soft Tissue Sarcomas of the Extremities. . . . . . . . . . .. 272 Laser Therapy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 279 A. Tuchmann, C. Armbruster, W Blauensteiner, and S. Kriwanek Experimental Basis of CO Laser Application 2 in Tumor Surgery. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 279 K. Dinstl and A. Tuchmann Experience with CO Laser in Tumor Surgery. . . . . . .. 283 2 H.-J. M eyer and R. Pichlmayr Nd: YA G Laser Application in the Surgical Treatment of Cancer. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 286 J.R. Anderson and e.G. Morran Neodymium: YA G Laser Therapy in Gastroduodenal Cancer. . . . . .. 290