REPORTS ON SEMINARS
(1) Seminar on "Advances and New Techniques in Radiation oncology Research"
A joint seminar was held in Seattle, Washington, from May 2-4, 1984, to discuss radiation research. Attention was focused on the basic and applied aspects of new radiation techniques.
A considerable discussion dealt with neutron therapy trials in the United States and Japan. Structural organization and planning of such efforts were discussed by Drs. Wooton, Ito, and Hall. Specific protocols and preliminary clinical experiences were described by Drs. Ishikawa, Tsunemoto, Griffin, Laramore, Morita, and Peters.
Issues of hyperthermia and chemical sensitizers plus radiotherapy likewise received considerable attention. Most of the former topic considered the physical devices and technology for heating and monitoring patients. Drs. Stewart, Onoyama, and Abe described these clinical experiences. A variety of putative radiation sensitizers including nitro-imidazoles, glutathione depletors, and others were also discussed. Both laboratory and clinical models were proposed for study in appropriate situations.
Unique, nonconventional radiation schedules (such as hyperfractionation) were discussed by Drs. Withers, Peters, and Sakamoto. Issues of normal tissue versus tumor injury were of crucial concern.
Finally, regional radiation therapy was discussed, both small field intra-operative and large field total body irradiation. Gastrointestinal cancers were the subject of the former and leukemia-lymphoma (in transplant preparation) the latter.
(2) Seminar on "Biochemical Modulation of Chemotherapy and Immunotherapy"
On November 19 and 20, 1984, at the Hotel New Otani in Tokyo, Japan, a seminar was held to discuss biochemical modulation of chemotherapy and immunotherapy. The first day concentrated on chemotherapy modulation and the second on immunotherapy and resistance-reversing mechanisms.
The majority of the first day highlighted issues related to biochemical modulation of pyrimidines, especially 5-fluorouracil (5-FU)-methotrexate (MTX) interactions, and reduced folate cofactors and 5-FU interactions. Dr. Friedman began the meeting with a broad outline of general principles which should be considered in the conduct of clinical modulatory trials. The identification of an appropriate laboratory biochemical parameter is a critical necessity for the most efficient conduct of this complicated sort of clinical investigations. He also presented the response-surface design statistical methodology as a mechanism for trial analysis.
Drs. Fujii, Cadman, Ota, and Akazawa discussed a variety of in vivo and in vitro studies which seek to define the site of biochemical modulation of antifols and fluoropyrimidines. Dr. Fujii described the F!!! alanine hepatic conversion of Ftorofur:
This degradation is catalyzed by dihydrouracil dehydrogenase and is blocked by uracil. In an attempt to favorably influence catabolism, he empirically used a combination of FT plus uracil. A ratio of 1:4 led to FT serum levels of 0.025 µg/ml and tumor level of 0.1 µg/gm. However, only preliminary Phase II studies have been conducted.
Dr. Ota reviewed two Japanese biochemical modulation trials. The first utilized MTX 20 to 1500 mg/m2 plus 5-FU 600 to 1500 mg/m2 (with a 1 to 3 hour interval) every week. Relatively few patients have been studied so far. The second study is a multicenter trial being planned with MTX doses of 30, 100, 300, and 1000 mg/m2 and 5-FU 600 mg/m2, with intervals of 3 or 7 hours. CF will be used for the higher MTX doses. It is anticipated that 50 colon and 100 gastric cancer patients will be evaluated.
Unfortunately, there is no definitive information available at this moment to suggest in which clinical circumstances a particular combination of 5-FU and MTX would be superior to the drugs used alone or simultaneously.
Larger amounts of data are being amassed in the United States, but the definitive Phase III trials have not yet been completed. The Japanese data are more preliminary, but interesting leads have been identified and there are at least two Phase III trials considered in gastric and colon cancer at this time.
Dr. Kovach then described a comprehensive series of experiments he has been performing with tiazofurin, attempting to perturb the intracellular guanine nucleotide pools. These studies could lead to some interesting clinical studies.
Dr. Kimura discussed his clinical studies with uracil plus FT (UFT) combinations and UFT plus MTX. He has initial data that 6 of 17 gastric cancer patients had a PR, but it is not certain whether the addition of MTX results in superior results (10 of 15 PR). Moreover, although the data of the uracil plus FT seems very interesting, it has not been studied in a formal, rigorously controlled way.
Dr. Mihich then described the work of his Roswell Park Memorial Institute collaborators exploring favorable folinic acid plus 5-FU interactions. Based on provocative preliminary data, clinical studies are ongoing at RPMI and other U.S. centers. Dr. Capizzi then described his ara-C studies with the attendant pharmacokinetic and biochemical analyses.
Drs. Sakurai and Mihich described in greater detail the intracellular target of ara-C action and the modulations of these actions by antimetabolites. MTX decreases purine nucleotide pools, while 5-FU decreases dTTP but not dCTP. MTX can also increase deoxycytidine kinase and ara-CTP, while reducing ATP, GTTP, dTTP, and dCTP.
The last portion of the first day was spent on the rationale for combinations of hormonal and chemotherapy for patients with breast cancer. Dr. Osborne provided a thorough and scholarly review of the difficulties in doing such trials and possible research opportunities that exist. Dr. Nomura described the Japanese experience to a combination chemoendocrine trial, which was equivalent to the U.S. experience. The last presentation of the first day was by Dr. Ohsawa who described a new combination of estradiochlorambucil which he calls "Bestrabucil", which seems to have homing properties specific to breast cancer tissue. However, and not explained at all in any of the subsequent discussions, this conjugate seems to seek tumor tissue of all sorts, wherever it is (in the rodent body). A series of the preclinical experiments are being conducted, trying to explain this observation. Dr. Ohsawa suggested that the butyrate moiety on this molecule makes it specifically "attractive" to tumors. This hypothesis generated some skepticism but a good deal of interest as well.
The second day was devoted to issues of immunomodulations and immunotherapy, specifically with interferons or the interferon inducers. Dr. Kataoka described his in vivo and in vitro experimentation with chemotherapy and!!
!and!!
!interferon. Dr. Ishida described the antitumor effects of the OK-432, a substance which is used widely in Japan and which is believed, in part, to be a!!
!interferon inducer.
Dr. Kovach described the laboratory and preliminary clinical findings of combinations of chemotherapy plus interferon. Combinations of DFMO plus IFN, or adriamycin or CDDP or alkylator plus IFN seem to be synergistic. A clinical study of BCNU plus IFN has been initiated at the Mayo Clinic. Dr. Katoaka described a series of vincristine plus interferon studies ongoing in Japan. He postulates that IFN could modify the cell membrane (changing fluidity or microfilaments) or derange metabolism (modifying DNA synthesis, cyclic AMP, prostaglandin E, and 2'-5' adenine). He believes that the major effect is on the microfilaments.
Dr. Makota Ogawa provided a comprehensive overview of the clinical experience with the interferon products in Japan. This was a most useful resume, since an enormous amount of information has been gained. These products have been tested in this way in Japan:
|
Phase
|
Alpha
|
Beta
|
Gamma
|
|
I
|
MOR-22
|
GKT-B
|
GI3 (Genentech)
|
|
II
|
HLBI
|
|
IF (Kyowa)
|
|
III
|
HLBI
|
|
|
|
IFN-A
|
|
S (Biogene)
|
A large, multi-institutional Phase II master protocol employed HLBI at 3 x 106 U/day.
|
Disease
|
N
|
CR
|
PR
|
|
Myeloma
|
73
|
1
|
3
|
|
NHL
|
32
|
1
|
2
|
|
ATL
|
10
|
1
|
2
|
| AML |
19
|
0
|
1
|
| Renal |
56
|
4
|
7
|
| Hepatoma |
7
|
0
|
0
|
| Breast |
19
|
0
|
0
|
Of particular interest is the fact that interferon has been nearly uniformly ineffective in lymphoma patients in Japan, an experience which is in marked contrast to that described in the United States. However, at least one explanation of this fact is that in Japan most of the lymphomas are the T cell variety and the diffuse undifferentiated varieties. In the United States, of course, the NPDL tumors are much more common and are sensitive to interferon.
The final five presentations concerned mechanisms of modulating the sensitivity to chemotherapy and circumventing resistance through membrane or microtubule manipulation. Dr. Tsukagoshi presented data of Dr. Tsuruo summarizing the role of calcium antagonists in reversing the resistance to anthra-cyclines. Drs. Sampi and Horikoshi described a preliminary clinical experiment looking at a limited number of patients who have received both a calcium channel blocker (Nifedipine) and chemotherapy (either adriamycin or vincristine). Unfortunately, there is not enough data at this time to permit firm conclusions. Significant toxicity has been noted (cardiovascular) and some responses observed. Dr. Inabe described the reversal of acquired resistance of tumor to vincristine and adriamycin by the addition of anthracycline derivatives or metabolites (which themselves possess no antitumor effect). Lastly, Dr. Sato described his dedicated efforts to deliver more drug to tumors by use of hypertensive agents, especially angiotensin II.
At the programmatic review held on November 21 after the scientific meeting, the following critiques and comments were made. There had been insufficient time for full discussion of some issues, and it was recommended that longer discussion periods be set aside. Potentially fewer presentations would be scheduled to permit more exchange of information at future meetings. This was approved. Secondly, it was suggested that, if it is at all possible, hard copies of the slides that the speakers would be using should be prepared and distributed ahead of time. This would permit a record of information to be available without the need for frantic attempts to transcribe data from slides (in a dark room). This was agreed to. Thirdly, attempts will be made to enlarge the audience to include more observers and nonspeaking participants (especially those younger faculty members who have specific areas of interest coinciding with the topic covered in the seminar). The desirability of having a larger educational forum was recognized by everyone and was generally agreed to.
(3) Seminar on “New Drug and Biologic Response Modifier Development”
A program review of issues associated with drug development was held in Oahu, Hawaii on February 25-26, 1985. A large compendium of hard copies of slide materials presented by the speakers was distributed at this meeting (as recommended at the previous meeting) and is available for review.
The first day included a wide ranging discussion of potential benefits and pitfalls of innovative screening procedures for identifying new agents of interest. Drs. Boyd, Sikic, and Collins described the new screens to be employed at NCI and other institutions, including the value of human tumor cloning systems disease-specific cell line models and preclinical pharmacology. The modified screen and the Blood Level Working Group activities were discussed. A general discussion then took place on the methodology of Phase I-II human studies--with special reference to the pediatric patient population. Drs. Ogawa and Majima discussed the guidelines proposed for such studies in Japan.
Various new, intensive, or investigational clinical approaches were then discussed with bone marrow transplantation (Drs. Bast and Masaoka), monoclonal antibodies (Dr. Ueda), and biologic response modifiers (Drs. Herberman and Ogawa). Approaches and clinical data from the United States and Japan were compared and contrasted.
The last part of the first day and the entire second day was devoted to specific new agents. An exciting array of new agents was discussed by Drs. Sakurai, Tanaka, Majima, and Yamada. Comparisons between clinically tested platinum analogues were discussed by Drs. Ogawa and Friedman, and anthracycline analogues by Drs. Majima, Ogawa and Masaoka, Yamada, Ogawa, and Friedman.
A general discussion of new agents and promising future directions by Drs. Mihich and Friedman concluded the scientific exchange. In closing, the retirement of Dr. Sakurai was announced and his vast contributions to the US-Japan exchange were noted with appreciation.
SEMlNAR AGENDA AND PARTICIPANTS
(1) SEMINAR ON ADVANCES AND NEW TECHNIQUES IN RADIATION ONCOLOGY RESEARCH
Seattle, Washington, May 2-4, 1984
AGENDA
I. Fast Neutron Beam Radiotherapy
U. S. Co-Chairman: Dr. Stewart
|
|
Physical Aspects of the University of Washington Clinical Neutron Beam Therapy Facility |
Peter Wootton, B.Sc. |
|
Treatment Planning System for Fast Neutron Therapy in Use in Japan |
Akira Ito, Ph.D. |
|
The Radiobiological Aspects of the New Generation of Hospital Based p+ ----> Be Generators |
Eric J. Hall, D.Sc. |
|
Evaluation of Fast Neutron Therapy for Carcinoma of the Esophagus |
Tatsuo Ishikawa, M.D. |
|
Present Status of Fast Neutron Therapy in Japan |
Hiroshi Tsunemoto, M.D. |
|
Clinical Aspects of Fast Neutron Radiotherapy: Current Results and Future Directions |
Thomas Griffin, M.D. |
|
Clinical Aspects of Fast Neutron Radiotherapy: Current Results and Future Directions |
George Laramore, M.D., Ph.D. |
|
Clinical Experience with Fast Neutron Beam on Carcinoma of the Uterine Cervix |
Sinroku Morita, M.S. |
|
Selection of Patients for Neutron Clinical Trials |
Lester Peters, M.D. |
II. Hyperthermia and Radiotherapy
U. S. Co-Chairman: Dr. Withers |
|
Combined Hyperthermia and Radiation: Prognostic Factors for Complete Response |
James R. Oleson, M.D., Ph.D. |
|
Development of an RF Capacitive Heating Device, Thermotron RF-8 |
Hirokazu Kato, Ph.D. |
|
Overview of the University of Utah Research Program in Hyperthermia |
J. Robert Stewart, M.D. |
|
Thermal Distribution After Heating with a Thermotron RF-8 |
Hirokazu Kato, Ph.D. |
|
The Bioengineering and Clinical Research Program in Hyperthermia |
Kenneth H. Luk, M.D. |
|
Clinical Experiences of Hyperthermia in Cancer Radiotherapy with some Considerations of Thermal Dosimetry |
Yasuto Onoyama, M.D. |
|
Clinical Results of Hyperthermia Combined with Radiation for Radioresistant Cancers |
Mitsuynki Abe, M.D. |
III. Radiation Sensitizers
U.S. Co-Chairman: Dr. Peters |
|
The Effects of New Radiosensitizers Developed in Japan on In Vitro and In Vivo Experimental System |
Kiyohiko Sakamoto, M.D. |
|
Radiation Sensitizers: Future Prospects |
J. Martin Brown, Ph.D. |
|
Thymine Hydroxylation as a Chemical Measure of Radiosensitization and Protection |
Tsutomu Kagiya, Ph.D. |
|
Radiosensitization Effects of BSO (DL-buthionine sulfoximine) as an Inhibitor of Glutathione Synthesis in Combination with Hypoxic Cell Sensitizers |
Chikara Komuro, Ph.D. |
|
Radiation and Sensitizers in Mutant Human Cells |
Eric J. Hall, D.Sc. |
|
Screening of PLD Repair Inhibitors In Vitro and In Vivo for Clinical Use |
Tsutomu Sugahara, M.D. |
IV. Dose Fractionation Effects in Normal Tissues and Tumors
U.S. Co-Chairman: Dr. Laramore |
|
Dose Fractionation Effects in Normal Tissues and Tumors |
H. Rodney Withers, M.D., D.Sc. |
|
Dose Fractionation Effects in Normal Tissues and Tumors |
Lester J. Peters, M.D. |
|
The Significance of Uneven Fractionation Regime on Cancer Chemotherapy |
Kiyohiko Sakamoto, M.D. |
V. Role of Computers in Treatment Planning
U. S. Co-Chairman: Dr. Griffin |
|
Clinical Aspects |
J. Robert Stewart, M.D. |
|
Application of the CT to Treatment Planning and Computer Controlled Conformation Therapy |
Tadayoshi Matsuda, M.D. |
|
Computers in Radiotherapy--The Fifth Generation |
Ira J. Kalet, Ph.D. |
VI. Intraoperative Radiotherapy
U. S. Co-Chairman: Dr. Luk |
|
Intraoperative Radiation Therapy for Locally Advanced Rectal Carcinoma |
Joel E. Tepper, M.D. |
|
Intraoperative Radiotherapy for Gastrointestinal Malignancy |
Mitsuyuki Abe, M.D. |
|
Experimental and Clinical Studies with Intraoperative Radiotherapy: The NCI Experience |
Timothy Kinsella, M.D. |
| VII. Total Body Irradiation and Bone Marrow Transplantation in the Treatment of Leukemia and Malignant Lymphomas |
|
Irradiation Techniques |
E. D. Thomas, M.D. |
|
Total Body Irradiation for Bone Marrow Transplantation in Leukemia: A Cooperative Study from the TBI Subcommittee in Japan |
Toshihiko Inoue, M.D. |
|
Clinical Aspects |
E. D. Thomas, M.D. |
(2) SEMINAR ON BIOCHEMICAL MODULATION OF CHEMOTHERAPY AND IMMUNOTHERAPY
Hotel New Otani, Tokyo, November 19-20, 1984
AGENDA
| Monday, November 19 |
| 9:00-9:10 |
Welcome and Opening Remarks |
Dr. Yoshio Sakurai |
| Chairman: Dr. R. Capizzi |
| 9:10-9:35 |
General principles of biochemical modulation trials |
Dr. Michael Friedman |
| 9:35-10:00 |
Biochemical modulation of effect of Ftorofur |
Dr. Setsuro Fujii |
| 10:00-10:25 |
The enhancement of 5-fluorouracil antitumor activity by methotrexate pretreatment |
Dr. Edwin Cadman |
| 10:25-10:45 |
Coffee Break |
|
| Chairman: Dr. M. Friedman |
| 10:45-11:10 |
Sequential methotrexate and 5-fluorouracil in Japan |
Dr. Kazuo Ota |
| 11:10-11:35 |
Sequential methotrexate and 5-fluorouracil in gastric cancer |
Dr. Shugo Akazawa |
| 11:35-12:00 |
Tiazofurin, a compound of potential value in manipulating guanine nucleotide pools |
Dr. John Kovach |
| 12:00-13:30 |
Noon Recess |
|
| Chairman: Dr. E. Cadman |
| 13:30-13:55 |
Clinical basis and effects of UFT and UFTM therapy for gastric cancer |
Dr. Kiyoji Kimura |
| 13:55-14:20 |
Metabolic modulation as a basis for improved protocol design: The example of 5-FU and folinic acid |
Dr. Enrico Mihich |
| 14:20-14:45 |
Self potentiation of high dose ara-C: Augmentation of its pharmacokinetics and biochemical pharmacology by its metabolites ara-U |
Dr. Robert Capizzi |
| 14:45-15:05 |
Coffee Break |
|
| Chairman: Dr. K. Ota |
| 15:05-15:30 |
Intracellular metabolism of anti-metabolites and nucleic acids in sequential chemotherapy |
Dr. Minoru Sakurai |
| 15:30-15:55 |
Target cell determinants of drug action and the design of clinical protocols: The example of ara-C |
Dr. Enrico Mihich |
| Chairman: Dr. Y. Nomura |
| 15:55-16:20 |
Combined chemoendocrine therapy of breast cancer: Rationale and pitfalls |
Dr. Kent Osborne |
| 16:20-16:30 |
Break |
|
| Chairman: Dr. K. Osborne |
| 16:30-16:55 |
Chemoendocrine therapy of breast cancer |
Dr. Yasuo Nomura |
| 16:55-17:20 |
Treatment of breast cancer with Bestra-bucil (estradiochlorambucil conjugate) |
Dr. Nakaaki Ohsawa |
Tuesday, November 20
Chairman: Dr. E. Mihich |
| 9:30-9:55 |
Chemotherapeutic and immunotherapeutic potency of interferon-!!!, !!!in murine solid tumors |
Dr. Tateshi Kataoka |
| 9:55-10:20 |
Antitumor effect of an IFN-!!!inducer -- OK-432 |
Dr. Nakao Ishida |
| 10:20-10:45 |
Enhancement of cancer drug cytotoxicity by interferon |
Dr. John Kovach |
| 10:45-11:05 |
Coffee Break |
|
| Chairman: Dr. J. Kovach |
| 11:05-11:30 |
Combined effect of interferon and vincristine on experimental tumor and the mode of action |
Dr. Tateshi Kataoka |
| 11:30-11:55 |
Overview of clinical experiences with interferons in Japan |
Dr. Makoto Ogawa |
| 11:55-13:30 |
Noon Recess |
|
| 13:30-13:55 |
Summary of the role of calcium antagonists in reversal of multi-resistance of tumor |
Dr. Shigeru Tsukagoshi |
| 13:55-14:20 |
Effect of calcium antagonists in chemotherapy |
Dr. Kazuni Sampi |
| 14:20-14:45 |
Effect of calcium antagonists in clinical chemotherapy |
Dr. Noboru Horikoshi |
| 14:45-15:05 |
Coffee Break |
|
| 15:05-15:30 |
Reversal of acquired resistance of tumor to vincristine and adriamycin by addition of anthracycline derivatives which have no antitumor effect |
Dr. Makoto Inaba |
| 15:30-16:00 |
Characteristic function of tumor blood vessel and induced hypertension chemotherapy with angiotensin II |
Dr. Haruo Sato |
| 16:00-16:15 |
Discussion |
|
| 16:15-16:45 |
Summary and Closing Remarks |
Dr. Michael Friedman |
| 16:45 |
Adjourn |
|
PARTICIPANTS
UNITED STATES - Speakers
Edwin C. Cadman, M.D.
Director of Cancer Research Institute
University of California at San Francisco
San Francisco, California 94143
Robert L. Capizzi, M.D.
Director of Oncology Research Center at Wake Forest University
Bowman Gray School of Medicine
Winston-Salem, North Carolina 27103
Michael A. Friedman, M.D.
Chief, Clinical Investigation Branch
Cancer Therapy Evaluation Program
Division of Cancer Treatment
National Cancer Institute
Landow Building, Room 4A04, NIH
Bethesda, Maryland 20892
John S. Kovach, M.D.
Division of Developmental Oncology Research
Mayo Clinic
Rochester, Minnesota 55905
Enrico Mihich, M.D.
Director, Grace Cancer Drug Center
Roswell Park Memorial Institute
666 Elm Street
Buffalo, New York 14263
Kent C. Osborne, M.D.
Department of Surgery
University of Texas in San Antonio
San Antonio, Texas 78284
JAPAN - Speakers
Shugo Akazawa, M.D.
Section Chief
Saitama Cancer Center Hospital
Inamachi, Kita-Adachi-gun
Saitama Pref. 362
Setsuro Fujii, M.D.
Professor Emeritus of Osaka University
The Osaka Foundation for Promotion of Fundamental Medical Research
Karasaki 1-1-1, Otsu
Shiga Pref. 520-01
Noboru Horikoshi, M.D.
Section Chief
Division of Clinical Chemotherapy
Cancer Chemotherapy Center;
Section Chief
Department of Clinical Oncology
Cancer Institute Hospital;
Japanese Foundation for Cancer Research
Kami-Ikebukuro 1-37-1
Toshima-ku, Tokyo 170
Makoto Inaba, Ph.D.
Chief-in-Research
Division of Experimental Chemotherapy
Cancer Chemotherapy Center
Japanese Foundation for Cancer Research
Kami-Ikebukuro 1-37-1
Toshima-ku, Tokyo 170
Nakao Ishida, M.D.
President
Tohoku University
Seiryo-cho 4-1
Sendai, Miyagi Pref. 980
Tateshi Kataoka, Ph.D.
Chief-in-Research
Division of Experimental Chemotherapy
Cancer Chemotherapy Center
Japanese Foundation for Cancer Research
Kami-Ikebukuro 1-37-1
Toshima-ku, Tokyo 170
Kiyoji Kimura, M.D.
Director
Nagoya National Hospital
San-no-Maru 4-1
Naka-ku, Nagoya 460
Yasuo Nomura, M.D.
Section Chief, Department of Surgery
National Kyushu Cancer Center Hospital
Nodame 959
Minami-ku, Fukuoka 815
Makoto Ogawa, M.D.
Chief, Division of Clinical Chemotherapy
Cancer Chemotherapy Center;
Acting Head, Department of Clinical Oncology
Cancer Institute Hospital
Japanese Foundation for Cancer Research
Kami-Ikebukuro 1-37-1
Toshima-ku, Tokyo 170
Nakaaki Ohsawa, M. D.
Associate Professor
Department of Internal Medicine, III
Faculty of Medicine
The University of Tokyo
Hongo 7-3-1
Bunkyo-ku, Tokyo 113
Kazuo Ota, M.D.
Vice Director
Aichi Cancer Center Hospital
Tashiro-cho, Kanokoden
Chikusa-ku, Nagoya 464
Minoru Sakurai, M.D.
Professor, Department of Pediatrics
Mie University School of Medicine
Edobashi 2-174
Tsu, Mie Pref. 514
Yoshio Sakurai, Ph.D.
Scientific Advisor, Cancer Institute
Cancer Chemotherapy Center
Kami-Ikebukuro 1-37-1
Toshima-ku, Tokyo 170
Kazuni Sampi, M.D.
Section Chief, Department of Hematology
Saitama Cancer Center Hospital
Inamachi, Kita-Adachi-gun
Saitama Pref. 362
Haruo Sato, M.D.
Director
Fukushima Rosai Hospital
Uchigo, Iwaki
Fukushima Pref. 973
Shigeru Tsukagoshi, Ph.D.
Chief
Division of Experimental Chemotherapy
Cancer Chemotherapy Center
Japanese Foundation for Cancer Research
Kami-Ikebukuro 1-37-1
Toshima-ku, Tokyo 170
Observers
Kohji Ezaki, M.D.
Associate Professor
Department of Internal Medicine
Fujita Gakuen University Hospital
Dengaku-ga-kubo, Kutsukake-cho
Tokoake, Aichi Pref. 470-11
Shuichi Fujimoto, Ph.D.
Chief, Department of Chemotherapy
Chiba Cancer Center Research Institute
Nitona-cho 666-2
Chiba 280
Jiro Inagaki, M.D.
Section Chief
Division of Clinical Chemotherapy
Cancer Chemotherapy Center;
Section Chief, Department of Oncology
Cancer Institute Hospital
Japanese Foundation for Cancer Research
Kami-Ikebukuro 1-37-1
Toshima-ku, Tokyo 170
Katsuhiro Inoue, M.D.
Section Chief
Division of Clinical Chemotherapy
Cancer Chemotherapy Center;
Section Chief, Department of Oncology
Cancer Institute Hospital
Japanese Foundation for Cancer Research
Kami-Ikebukuro 1-37-1
Toshima-ku, Tokyo 170
Hisashi Majima, M.D.
Clinical Director
Chiba Cancer Center
Nitona-cho 666-2
Chiba 280
Haruhiko Sato, M.D.
Department of Clinical Cancer Chemotherapy
The Research Institute for Tuberculosis and Cancer
Tohoku University
Seiryo-cho 4-1
Sendai 980
Hideya Tashiro, M.D.
Department of Surgery
National Kyushu Cancer Center Hospital
Nodame 959
Minami-ku, Fukuoka 815
Hironobu Toki, M.D.
Section Chief, Department of Medicine
Shikoku Cancer Center
Horinouchi 13
Matsuyama, Ehime Pref. 790
Clinical Staffs
Hitoshi Kamiya,
Hajime Kawasaki,
Tsutomu Nobori,
Toshiki Okubo
Department of Pediatrics
Mie University School of Medicine
Edobashi 2-174
Tsu, Mie Pref. 514
Seno, Takashi (Ph.D.)
Chief
Department of Immunology and Virology
Saitama Cancer Center Research Institute
Inamachi, Kita-Adachi-gun
Saitama Pref. 362
Koichi Adachi,
Takashi Nakamura,
Atsuhiko Tada,
Katsuni Ueno,
Hiroyuki Yamazaki
Division of Clinical Chemotherapy
Cancer Chemotherapy Center and Department of Clinical Oncology
Cancer Institute Hospital
Japanese Foundation for Cancer Research
Kami-Ikebukuro 1-37-1
Toshima-ku, Tokyo 170
Tadashi Araki
Kureha Chemical Industries Co., Ltd.
Nihonbashi Horidome 1-9-11
Chuo-ku, Tokyo 103
Invited Guests
Iwao Abe
Research Cooperation Division
Japan Society for the Promotion of Science
Yamato Building, Kojimachi 5-3-1
Chiyoda-ku, Tokyo 102 Japan
Robert R. Omata, M.D.
Executive Secretary
US-Japan Cooperative Cancer Research Program
Office of International Affairs
National Cancer Institute
Building 31, Room 4A49, NIH
Bethesda, Maryland 20892 USA
Haruo Sugano, M.D.
Chairman, Japanese Steering Committee of the US-Japan Cooperative Cancer Research Program;
Director, Cancer Institute and
Director, Cancer Chemotherapy Center
Japanese Foundation for Cancer Research
Kami-Ikebukuro 1-37-1
Toshima-ku, Tokyo 170 Japan
(3) SEMINAR ON NEW DRUG AND BIOLOGIC RESPONSE MODIFIER DEVELOPMENT
Makaha, Oahu, Hawaii, February 25-26, 1985
Monday, February 25
GENUINE DRUG DEVELOPMENT TOPICS
|
| 9:00-9:05 |
Welcome and Opening Remarks |
Dr. M. Friedman |
| Chairman: Dr. Y. Sakurai |
| 9:05-9:40 |
New Directions for Preclinical Screening of Antitumor Agents at the NCI |
Dr. M. Boyd |
| 9:40-10:10 |
Role of Hunan Tumor Cell Models in Anticancer Drug Development |
Dr. B. Sikic |
| 10:10-10:40 |
Potential Roles for Preclinical Pharmacology in Phase I Clinical Trials |
Dr. J. Collins |
| 10:40-11:00 |
Coffee Break |
|
| Chairman: Dr. M. Boyd |
| 11:00-11:30 |
Phase I Trials in Pediatric Cancer Patients: A Rationale |
Dr. R. Ungerleider |
| 11:30-12:15 |
Methods and Criteria of Evaluation of Clinical Trials of Anticancer Drugs |
General Discussion |
| 12:15-1:15 |
Lunch |
|
| Chairman: Dr. K. Yamada |
| 1:15-1:45 |
Present Status of Bone Marrow Transplantation in Japan |
Dr. T. Masaoka |
| 1:45-2:15 |
Design and Execution of Phase I Trials in Autologous Bone Marrow Transplantation |
Dr. R. Bast |
| 2:15-2:45 |
Clinical Application of Monoclonal Antibodies in Japan |
Dr. R. Ueda |
| 2:45-3:00 |
Coffee Break |
|
| 3:00-3:30 |
Current Status and Plans for Clinical Trials with BRMs in USA |
Dr. R. Herberman |
| 3:30-4:00 |
Interferon Studies in Japan |
Dr. M. Ogawa |
| 4:00-4:20 |
New Antitumor Agents under Investigation with Experimental Tumors: RA-700,!!!-OHP, CSD |
Dr. Y. Sakurai |
| 4:20-4:40 |
New Antitumor Antibiotics under Development in Japan |
Dr. N. Tanaka |
| 4:40-5:00 |
Phase I Study of 590-S, a New Fluoropyrimidine |
Dr. H. Majima |
| 5:00-5:20 |
Phase I-II Studies of an ara-C Analogue, PL-AC in Hematologic Malignancies |
Dr. K. Yamada |
Tuesday, February 26
SPECIFIC DRUG DEVELOPMENT TOPICS
Chairman: Dr. T. Masaoka |
| 9:00-9:30 |
Studies with a New Platinum Compound -- 254S in Japan |
Dr. M. Ogawa |
| 9:30-10:00 |
Status of Platinum Analogues Studies in USA and Europe |
Dr. M. Friedman |
| 10:00-10:30 |
Phase I-II Study of THP - Adriamycin in Japan |
Dr. H. Majima |
| 10:30-11:00 |
Coffee Break |
|
| Chairman: Dr. R. Bast |
| 11:00-11:30 |
Oral VP-16 in NH Lymphoma and Small Cell Lung Cancer |
Dr. M. Ogawa |
| 11:30-12:00 |
Phase I-II Studies of SM-108, an IMP-dehydrogenase Inhibitor in Hematologic Malignancies |
Dr. K. Yamada |
| 12:00-12:30 |
4’ Epi-Adriamycin Study in Japan |
Dr. M. Ogawa and
Dr. T. Masaoka |
| 12:30-1:30 |
Lunch |
|
| Chairman: Dr. E. Mihich |
| 1:30-1:45 |
Phase II Study of Mitoxantrone in Acute Leukemia |
Dr. T. Masaoka |
| 1:45-2:00 |
Phase II-III Mitoxantrone Studies in Hematologic Malignancies |
Dr. K. Yamada |
| 2:00-2:20 |
Mitoxantrone Studies in Breast Cancer in Japan |
Dr. M. Ogawa |
| 2:20-2:30 |
Mitoxantrone Studies in the U.S. |
Dr. M. Friedman |
| 2:30-3:00 |
Coffee Break |
|
| Chairman: Dr. M. Friedman |
| 3:00-3:30 |
Phase I-II Drugs of Interest in U.S. |
Dr. M. Friedman |
| 3:30-4:00 |
New Directions for Drug Development |
Dr. E. Mihich |
| 4:00-4:30 |
General Discussion |
|
| 4:30-4:45 |
Summary and Closing |
Dr. Y. Sakarai |
PARTICIPANTS
UNITED STATES
Michael A. Friedman, M.D.
Chief, Clinical Investigations Branch
Cancer Therapy Evaluation Program
Division of Cancer Treatment
National Cancer Institute
Landow Bldg., Rm. 4A04
Bethesda, MD 20892
Robert C. Bast, Jr., M.D.
Professor of Medicine
Duke University Medical Center
Box 3843
Durham, NC 27710
Michael R. Boyd, M.D.
Associate Director for Developmental Therapeutics
Division of Cancer Treatment
National Cancer Institute
Landow Bldg., Rm. 5A21
Bethesda, MD 20892
Jerry M. Collins, M.D.
Chief, Pharmacokinetics Section
Clinical Pharmacology Branch
Division of Cancer Treatment
National Cancer Institute
Bldg. 10, Rm. 6N119
Bethesda, MD 20892
Ronald B. Herberman, M.D.
Acting Associate Director of the Biological Response Modifiers Program
Division of Cancer Treatment
National Cancer Institute
Frederick Cancer Center
Bldg. 560, 3193
Frederick, MD 21701
Enrico Mihich, M.D.
Director
Department of Experimental Therapeutics
Roswell Park Memorial Institute
666 East Street
Buffalo, NY 14203
Branimir Ivan Sikic, M.D.
Assistant Professor
Department of Medical oncology
Stanford University Medical Center
Stanford, CA 94305
Richard Ungerleider, M.D.
Head, Pediatric Section
Clinical Investigations Branch
Cancer Therapy Evaluation Program
Division of Cancer Treatment
National Cancer Institute
Landow Bldg., Rm. 4A20
Bethesda, MD 20892
JAPAN
Yoshio Sakurai, Ph.D.
Scientific Advisor, Cancer Institute
Japanese Foundation for Cancer Research
c/o Cancer Chemotherapy Center
Kami-Ikeburkuo 1-37-1
Toshima-ku, Tokyo 170
Makota Ogawa, M.D.
Chief, Division of Clinical Chemotherapy
Cancer Chemotherapy Center, and Acting Head, Department of Clinical Oncology
Cancer Institute Hospital
Japanese Foundation for Cancer Research
c/o Cancer Chemotherapy Center
Kami-Ikebukuro 1-37-1
Toshima-ku, Tokyo 170
Hisashi Majima, M.D.
Associate Director, Clinical
Chiba Cancer Center Hospital
Nitona-cho 666-2
Chiba 280
Tohru Masaoka, M.D.
Director of Internal Medicine
Center for Adult Diseases, Osaka
Nakamichi 1-3-3
Higashinari-ku, Osaka 537
Nobuo Tanaka, M.D.
Professor of Microbiology
Institute of Applied Microbiology
University of Tokyo
Yayoi 1-1-1
Bunkyo-ku, Tokyo 113
Ryuzo Ueda, M.D.
Section Chief
Division of Chemotherapy
Aichi Cancer Center Research Institute
Tashiro-cho Kanokoden
Chikusa-ku, Nagoya 464
Kazumasa Yamada, M.D.
Professor of Medicine
The Branch Hospital
Nagoya University School of Medicine
Daiko-cho 1-1-20
Higashi-ku, Nagoya 461