(1) Seminar on “Anticancer Drug Resistance”

A joint seminar on anticancer drug resistance was held in Honolulu, Hawaii, May 30 -June 1, 1983, as part of the treatment area component of the U.S.-Japan Cooperative Cancer Research Program. Principal scientific discussions were held on May 30 and 31, with the morning of June I being devoted largely to business matters. A copy of the seminar agenda and list of participants is attached. The scientific sessions were divided generally into a description/discussion of the phenomenon of drug resistance and to approaches to overcoming drug resistance. In many areas these topics overlapped extensively and central consideration was given to mechanisms of drug resistance throughout the seminar.
After some opening remarks by Drs. Chabner, Sakurai, and Hall, the scientific discussions were begun. Dr. Chabner gave a general overview of drug resistance with particular emphasis on the clinical implications. He devoted special attention to the phenomenon of pleiotropic drug resistance (PDR) and cited some specific areas of research as needing additional work. Dr. Clendenin then gave a short talk describing studies aimed at specifically reversing the PDR phenotype with agents Such as verapamil. An overall review of Japanese research on anticancer drug resistance was presented by Dr. Sakurai. He described a variety of studies but gave emphasis to evaluation of nitrogen mustard-resistant Yoshida sarcoma cells. In his talk he described experiments demonstrating the presence of pre-existing resistant cell populations in untreated tumors as well as selection of resistant cell lines with treatment. The observation of collateral sensitivity of nitrogen mustard-resistant cells to 6-mercaptopurine was of particular interest. Cross resistance to a variety of other alkylating agents including mitomycin C was also observed. Andrew Coldman then gave a presentation regarding the now well-known “Goldie-Coldman” mathematical model of drug resistance which incorporated several recent model improvements. Dr. Kuwano described work with somatic cell mutants with altered sensitivity to amphotericin B, vitamin A, and some other agents that have been reported to potentiate the effects of anticancer drugs. Cross-resistance patterns and membrane changes in drug-resistant L5178Y cells were the subject of Dr. Tanaka’s talk. He cited increased drug efflux as the probable mechanism responsible for the resistance. In these cells, rather broad cross-resistance was associated with increased glycoprotein synthesis, but the presence of a specific membrane glycoprotein marker was not established. Dr. Suffness gave an overview of the implications of drug resistance for the discovery and development of new anticancer agents, drawing an analogy to problems which exist in the treatment of infectious diseases. Dr. Nishizuka then discussed the role of calcium and phospholipid turnover in control of cell proliferation. He emphasized the importance of the cell membrane as a signal transducer. The final scientific presentation of this session was made by Dr. Tsukagoshi. He described collateral sensitivities of drug-resistant sub-lines of murine P388 and L1210 leukemia.
Dr. Umezawa opened the second scientific session with a report on studies of drug uptake and efflux in resistant cell lines. In his opening remarks he cited several factors important in new drug screening, including the potential difficulties in mouse-man correlations and the potential value of effective screening models for specific malignancies such as gastric cancer. He also discussed the value of incorporating drug-resistant cells into new drug screening efforts. He then presented very detailed uptake/efflux studies of THP, an adriamycin analog, including comparative studies in several different drug-resistant cell lines. Increased drug efflux was cited as a common mechanism of resistance. Dr. Driscoll reported on studies of 5-azapyrimidine nucleosides in drug-resistant cell lines which were important determinants in the development of such compounds as anticancer drugs. Dr. Inaba described results of studies with P388/ADR (adriamycin-resistant P388 cells) and presented a model for the mechanism of drug resistance, also based on increased drug efflux in resistant cells. Dr. Shoemaker then described evidence from a variety of experimental models indicating that PDR also occurs in human tumor cell populations. Studies of PDR in human cells were reported to be at a relatively early stage, with no solid evidence yet available regarding the mechanism of resistance. Dr. Tsuruo gave a talk regarding reversal of drug resistance with calcium antagonists. He described a variety of agents useful in this regard including some anticalmodulin compounds. He presented a hypothesis regarding the mechanism of this phenomenon based on “circumvention of heterogeneity” in drug response in the tumor cell population. Dr. Kuwano reported on studies of the effects of a calcium channel blocker (verapamil) and amphotericin B on DNA-mediated gene transfer. Enhanced transfer was observed with these agents as well as some related compounds. Dr. Hall gave a broad overview of drug resistance from both the clinical and basic science viewpoint. He reviewed general concepts of drug resistance and discussed specific drugs where the mechanism of resistance has been relatively well characterized. He concluded by suggesting some therapeutic strategies for overcoming drug resistance. Dr. Hoth gave a brief update on new U.S. investigational drugs and the status of clinical trials. Dr. Shoemaker then presented an overall review of the seminar, highlighting some outstanding areas requiring further research such as the mechanism(s) of PDR, resistance to single agents in human tumor cell populations, the therapeutic significance of collateral sensitivity, and the potential value of drug-resistant cells (particularly PDR cells) in new drug screening. This was followed by a general discussion by all seminar participants and closing remarks by Drs. Driscoll and Sakurai.
(2) Seminar on “Current Status of Chemotherapy for Curable Cancers”
It is well-known that the first success of chemotherapy on malignant diseases was attained in cases of neoplasms of hematopoietic tissues. However, the recent application of new anticancer drugs in combination revealed an evidence of effect even to the solid cancers, especially children’s cancers and adult cancers of the specified organs.
The recent supply of cis-platinum for clinical use put a new light on the treatment of cancers of the ovary and testis, or the small cell lung cancer. The aim of this seminar was to exchange the newest information on the clinical experiences of successful chemotherapeutic treatment of these cancers most responsive to chemotherapy.
Small Cell Lung Cancer:
Dr. Ihde summarized the present status of chemotherapy of this tumor in the United States. Drs. Saijo, Horikoshi, Kimura, and Nishimura presented their own trials and joined discussions, which came to the following conclusion.
In the treatment of SCLC, chemotherapy is the first choice irrespective of the histologic types, the limited or extended disease. The drugs applied for combination regimen are cDDP, VCR, CPM, ADM, VP-16, and MTX. ACNU is also used in Japan. As for the intensity of treatment, the high dose therapy induced high response rate, but it did not necessarily mean the prolongation of life-span or the rate of cure.
It was suggested that radiation to the localized tumor after successful chemotherapy seemed to be profitable, but radiation prior chemotherapy was not recommended. Dr. Ihde also stated that the late intensification with autologous bone marrow transplantation has not shown any encouraging result. Cranial irradiation to prevent the brain metastasis extended the disease free interval, but it did not prolong the total life-span of the patients. The dose might be less than 2,000 rads, considering the delayed side-effect of radiation to the brain tissue. He reported 26 cases of long survivors out of 205 cases in the United States, but it must be noted that the recurrence after 31 to 62 months remission was sometimes observed.
Ovarian Cancer:
Drs. Young, Inagaki, Sugimori, and Ota gave their presentation about their clinical experiences. The best treatment seemed to be the chemotherapy with combination regimen using CPM, ADM, and cDDP. or HMM, CPM, MTX, and 5-FU. Dr. Young recommended to make choice of CPM or cDDP as the main components of the combination for the treatment of this disease.
Therapy of the peritonitis carcinomatosa should be investigated further, which occurs frequently among the patients with ovarian cancer due to the anatomical location of the tumor. Which drugs are the most effective to the peritonitis has not yet been confirmed, but MTX, 5-FU, ADM, and cDDP were commonly used in the States, and MMC in Japan.
The time of second look operation (SLO) was discussed. Dr. Young suggested that SLO might be done 9 to 10 months after the complete response came. The site of the original tumor and the surrounding adhesion should be histologically examined by biopsy.
Dr. Young has established several culture lines of the ovarian cancer from the patients, with which he is studying the acquisition of drug resistance during clinical treatment. If the overcome of the resistance by calcium channel blockers is realized with these culture lines, it might be promising to apply this procedure during clinical treatment of the patients with ovarian cancer.
Testicular Tumors:
This tumor is the most responsive tumor among the three tumors discussed in this seminar. Drs. Golbey, Kawabe, Aso, and Kotake joined the discussions with each of their clinical experiences. MSKCC has had a long experience of chemotherapy of this tumor since 1955 and the present regimen is composed of VLB, ACD, BLM, and cDDP, the so-called VAB III. A combination of cDDP, VLB, and BLM (PVB) was introduced by Dr. Einhorn which is now most popularly used. Presently, it cannot be said which one has more merits, VAB or PVB, but there were the patients with the recurrence of tumor who responded to the second therapy with the higher dose of cDDP after the prior chemotherapy with PBV. It might be due to the comparatively low dose of cDDP in PVB regimen. The effect of maintenance therapy after complete response on the rate of recurrence is somewhat ambiguous. According to the data either of Dr. Golbey or Dr. Einhorn, the recurrence rate was not so far influenced by the maintenance therapy.
The surgical operation of the patients who stayed in the state of partical response by chemotherapy showed the samely good result as that of the patients in complete response. It was suggested that the adjuvant surgery is an useful measure in the treatment of testicular tumors.
The common impression in this seminar was that we might be able to develop hereafter a promising method of treatment of solid cancers in general by analysing the most effective regimens and also the behavior of these three tumors under the successful chemotherapy.
(3) Seminar on “Development of New Anticancer drugs and Biologic Response Modifiers
A seminar on the development of new anticancer drugs and biologic response modifiers was held in Tokyo, Japan, February 9-10, 1984, as the major component of the annual program review held at that time. The agenda and list of participants are attached.
The first morning was devoted to a review of selected screening methods. The initial papers covered NCI’s selective acquisition methods and the recently revised screening panel that involves a smaller number of in vivo systems and adds the human tumor colony forming assay for selected materials. New models being pursued include possible in vivo cell differentiation tests and metastasis models. A more detailed review of the stem cell assay, under investigation in both countries, then occurred. Japanese studies are directed toward the use of the assay for prediction of clinical response, while studies at the NCI are focused on new drug screening. Technical problems continue to occur, but progress is being made. Because of the variation in success among tumor types, U.S. studies are now limited to melanoma, ovary. colorectal, kidney. lung, and breast tumors. The final paper of the morning discussed the use of “rational” doses, based on blood level determinations, in human tumor xenografts, with the objective of carrying out such tests between phases I and II.
The afternoon session began with discussions of preclinical and clinical data on flurouracil analogs and derivatives, including 1-phthalidyl 5-FU (590-S), 3-phthalidyl 5-FU, 5’-DFUR, oral ftorafur, and UFT. Clinical phase II studies with 5’-DFUR resulted in objective responses in breast and colorectal cancers, suggesting the need for randomized phase III studies. The remainder of the afternoon session was devoted to differentiating agents. It was reported that certain cytotoxic agents at subtoxic doses inhibited DNA but not RNA or protein synthesis. Also, phorbol esters (e.g., TPA) and retinoic acid could induce differentiation without inhibiting DNA synthesis. It was agreed that differentiation was an area worthy of further exploration.
The second morning was devoted to biological response modifiers, the major emphasis being on updating the status of clinical and experimental studies with the various interferons and monoclonal antibodies. Data are not yet sufficient to draw many conclusions, but work is progressing rapidly.
The second afternoon was devoted primarily to discussions of various new drugs. Drugs discussed by the Japanese investigators included N4 palmitoyl Ara-C, a mitomycin C analog (M-83), an imidazole (SM-108), a platinum derivative (1-OHP), and an adriamycin derivative (THP-Adr). Reports on new drugs in clinical trial in the United States included n-methyl formamide and homoharringtonine. In addition, clinical data were reported from both countries on mitoxantrone.
The final portion of the program consisted of a discussion of the gastric cancer trial carried out jointly in both countries. This trial, although not a positive study, demonstrated the feasibility of performing such joint clinical studies, albeit with difficulty.


Honolulu, Hawaii*, May 30 - June 1, 1983


Monday, May 30
Morning Session (Chairmen: Drs. Sakurai and Chabner)
9:00-9:15 Opening Remarks (Japan and U.S.)
9:15-9:45 “Clinical implications of drug resistances” Dr. Chabner
10:00-10:20 “Review of Japanese studies of cancer cell drug resistance” Dr. Sakurai
10:30-11:00 Coffee Break
11:00-11:30 “Mathematical model for the development of drug resistance” Dr. Coldman
12:00-1:30 Lunch
Afternoon Session (Chairmen: Drs. Tanaka and Suffness)
1:30-1:50 “Somatic cell mutants with altered sensitivity to amphotericin B, vitamin A and related agents that potentiate anticancer drugs” Dr. Kuwano
2:00-2:20 “Cross-resistance patterns and alterations of plasma membrane of drug resistant L5178Y cells” Dr. Tanaka
2:30-3:00 “Implications of drug resistance to the discovery and development of new anticancer agents” Dr. Suffness
3:15-3:45 Coffee Break
3:45-4:05 “Calcium and phospholipid turnover in transmembrane control of cellular functions and proliferation. A mechanism of action of phorbol esters” Dr. Nishizuka
4:15-4:35 “Collateral sensitivity of P388/6MP to an antitumor derivative of imidazole and L1210/CDDP to an analog of platincomplex” Dr. Tsukagoshi

Tuesday, May 31
Morning Session (Chairmen: Drs. Umezawa and Driscoll)
9:00-9:20 “Influx and efflux of THP-ADM in resistant cell lines” Dr. Umezawa
9:30-10:00 “Collateral sensitivity of some resistant L1210 tumor models to 5-azapyrimidine nucleosides” Dr. Driscoll
10:15-10:35 “Possible mechanism for the broad cross-resistance between anthracyclines and vinca alkaloids” Dr. Inaba
10:45-11:15 Coffee Break
11:15-11:45 “The multi-drug resistant phenotype in human tumor cell populations” Dr. Shoemaker
12:00-1:30 Lunch
Afternoon Session (Chairmen: Drs. Nishizuka and Hoth)
1:30-2:00 “Drug resistance as a membrane and cell-sap phenomenon” Dr. Hall
2:15-2:35 “Reversal of acquired resistance to anthracyclines and vinca alkaloids by calcium modifiers” Dr. Tsuruo
2:45-3:05 “Do verapamil and polyene antibiotics enhance the efficiency of DNA-mediated gene transfer?” Dr. Kuwano
3:15-3:45 Coffee Break
3:45-4:15 “U.S. investigational new drug update” Dr. Hoth
4:30-4:45 “General discussion and conference summary” Dr. Driscoll
4:45-5:00 4:45-5:00

Wednesday, June 1
9:00-12:00 Japan
Dr. Sakurai
Dr. Umezawa
Dr. Tsukagoshi

Dr. Driscoll
Dr. Hoth
Dr. Suffness

12:00 Lunch at University of Hawaii
*May 30-3 1 technical sessions to be held at Prince Kuhio Hotel (Territorial III Room). June 1 business meeting to be held at University of Hawaii


Inaba, Makoto (Ph.D.): Chief-in-Research, Cancer Chemotherapy Center, Japanese Foundation for Cancer Research; Kami-Ikebukuro 1-37-1, Toshima-ku, Tokyo 170
Kuwano, Michihiko (M.D.): Professor, Department of Biochemistry, Medical College of Oita; Idaigaoka 1-1506, Hazama-cho, Oita-gun, Oita 879-56
Nishizuka, Yasutomi (M.D.): Professor, Department of Biochemistry, Kobe University School of Medicine; Kusunoki-cho 7-5-1, Chuo-ku, Kobe 650
Sakurai, Yoshio [Coordinator] (Ph.D.: Director, Cancer Chemotherapy Center, Japanese Foundation for Cancer Research; Kami-Ikebukuro 1-37-1, Toshima-ku, Tokyo 170
Tanaka, Nobuo (M.D.): Professor, Institute of Applied Microbiology, The University of Tokyo; Yayoi 1-1-1, Bunkyo-ku, Tokyo 113
Tsukagoshi, Shigeru (Ph.D.): Chief, Division of Experimental Chemotherapy Cancer Chemotherapy Center, Japanese Foundation for Cancer Research; Kami-Ikebukuro 1-37-1, Toshima-ku, Tokyo 170
Tsuruo, Takashi (Ph.D.): Research Staff, Cancer Chemotherapy Center, Japanese Foundation for Cancer Research; Kami-Ikebukuro 1-37-1, Toshima-ku, Tokyo 170
Umezawa, Hamao (M.D.): Director Institute of Microbial Chemistry; Karni Osaki 3- 14-23 Shinagawa-ku, Tokyo 141

Chabner, Bruce (M.D.): Director, Division of Cancer Treatment, National Cancer Institute National Institutes of Health Bethesda, Maryland 20205
Coldman, Andrew: Cancer Control Agency of British Columbia, Department of Epidemiology
2656 Heather Street, Vancouver, British Columbia, Canada V5Z 3J3
Driscoll, John (Ph.D.): Acting Associate Director, Developmental Therapeutics Program, Division of Cancer Treatment, National Cancer Institute, NIH
Bethesda, Maryland 20205
Hall, Thomas (M.D.): Director, Cancer Control Program, University of Hawaii at Manoa Honolulu, Hawaii 96813
Hoth, Daniel (M.D.): Chief, Investigational Drug Branch, Cancer Therapy Evaluation Program, Division of Cancer Treatment, National Cancer Institute, NIH
Bethesda, Maryland 20205
Shoemaker, Robert (Ph.D.): Head, Cell Culture Section, Drug Evaluation Branch Developmental Therapeutics Program, Division of Cancer Treatment National Cancer Institute, NIH
Bethesda, Maryland 20205
Suffness, Matthew (Ph.D.): Chief, Natural Products Branch, Developmental Therapeutics Program, Division of Cancer Treatment, National Cancer Institute, NIH
Bethesda, Maryland 20205

Tokyo/Nagoya, December 5-8(9), 1983

Monday, December 5
Afternoon Institute Visit and Discussion Cancer Chemotherapy Center, Cancer Institute Hospital (Japanese Foundation for Cancer Research; Tokyo)
Evening Dinner (Hosted by Dr. Y. Sakurai)

Tuesday, December 6
SEMINAR - Tokyo Session [International House; Tokyo]
9:00 Opening and Introductory Remark Yoshio Sakurai (Cancer Chemotherapy Center)
Chairpersons: R. C. Young & Makoto Ogawa
1. Small Cell Carcinoma
9:10 Current Status in U.S.A. (20 min) Daniel C. Ihde (NCI)
9:30 Current Status in Japan (15 min) Nagahiro Saijo (National Cancer Center, Japan)
9:45 (10 min) Noboru Horikoshi (Cancer Chemotherapy Center)
9:55 Discussion (20 min)
10:15 Coffee Break (20 min)
2. Ovarian Cancer
10:35 Current Status in U.S.A. (20 min) Robert C. Young (NCI)
10:55 Current Status in Japan (20 min) Jiro Inagaki (Cancer Chemotherapy Center)
11:15 Discussion (20 min)
11:35 Lunch
3. Testicular Cancer
13:00 Current Status in U.S.A. (20 min) Robert B. Golbey (Memorial Sloan-Kettering Cancer Center)
13:20 Current Status in Japan (20 min) Kazuki Kawabe (Tokyo University Hospital)
13:40 Discussion (20 min)
14:00 Summary and Closing Remark (15 min) Makoto Ogawa (Cancer Chemotherapy Center)
14:15 Adjourn
16:00-18:00 Move to Nagoya
19:00- Reception at Nagoya Castle Hotel

Wednesday, December 7
SEMINAR - Nagoya Session [Nagoya Castle Hotel]
9:00 Opening and Introductory Remark Kiyoji Kimura (Nagoya National Hospital)
Chairpersons: R. B. Golbey & Makoto Ogawa
1. Small Cell Carcinoma
9:10 Current Status in U.S.A. (20 min) Daniel C. Ihde (NCI)
9:30 Current Status in Japan (15 min) Ikuro Kimura (Okayama University )
9:45 (15 min) Minoru Nishimura (Aichi Cancer Center)
10:00 Discussion (20 min )
10:20 Coffee Break (20 min)
2. Ovarian Cancer
10:40 Current Status in U.S.A. (20 min) Robert C. Young (NCI)
11:00 Current Status in Japan (15 min) Hajime Sugimori (Saga University )
11:15 (15 min) Yutaka Tomoda (Nagoya University)
11:30 Discussion (20 min )
11:50 Lunch
3. Testicular Cancer
13:30 Current Status in U.S.A. (20 min) Robert B. Golbey (Memorial Sloan-Kettering Cancer Center)
13:50 Current Status in Japan (15 min) Toshihiko Kotake (Center for Adult Diseases, Osaka )
14:05 (15 min) Yoshio Aso (Hamamatsu Univ. School of Med.)
14:20 Discussion (20 min )
14:40 Coffee Break (20 min)
4. Round Table Discussion: Recent Results on Breast and Gastrointestinal Tumors
15:00 On Breast Cancer Katsuhiro Inoue (Cancer Chemotherapy Center)
Shoji Suga (Nagoya National Hospital)
16:15 Summary and Closing Remarks (15 min) U.S. Participants
16:30 Adjourn
Thursday, December 8 Institution Visits to Cancer Clinics in Nagoya, Kyoto, or Osaka.

Keidanren Kaikan Rm. 901, Tokyo, February 9- 10, 1984

Thursday, February 9
9:30 Welcome and Opening Remarks Dr. Y. Sakurai
Dr. S. Schepartz
Chairpersons: Dr. Narayanan & Dr. Sakurai
9:40 l) New approaches to the selection of compounds for testing and discussion of selected new drugs.
Discussion (25 min)
Dr. V. Narayanan (DCT, NCI)
10:05 2) New approaches to screening and preclinical results with selected agents.
Discussion (25 min)
Dr. M. Wolpert (DCT, NCI)
10:30 Coffee Break (1 5 min)
10:45 3) Stem cell assay in human ovarian cancer.
Discussion (20 min)
Dr. K. Inoue (Cancer Chemotherapy Center)
11:05 4) Human tumor stem cell assay in U.S.
Discussion (25 min)
Dr. M. Wolpert (DCT, NCI)
11:30 5) Rational approach to evaluation of responsiveness of human tumor xenografts to chemotherapy.
Discussion (20 min )
Dr. M. Inaba (Cancer Chemotherapy Center)
11:50 General Discussion
12:00-13:00 Lunch (Rm. 906)
Chairpersons: Dr. Kimura & Dr. Bloch
13:00 1) 590-S:
a) Antitumor activity of phthalidyl 5FUs, new derivatives of 5 FU, on experimental animal tumors. (15 min) Dr. K. Nitta (National Cancer Center)
b) Clinical study of 590-S.(5 min)
Discussion (10 min)
Dr. H. Majima (Chiba Cancer Center)
13:30 2) 5’-DFUR: Preliminary report on a phase II study of oral 5’-deoxy-fluorouridine.
Discussion (25 min)
Dr. K. Ota (Aichi Cancer Center)
13:55 3) UFT:
a) Combination of 5-FU derivative with uracil (UFT). (20 min) Dr. S. Fujii (Osaka University )
b) UFT, A new anticancer drug and its clinical application. (20 min)
Discussion (10 min)
Dr. K. Kimura (National Nagoya Hospital)
14:45 Coffee Break (15 min)
Chairpersons: Dr. Oettgen & Dr. Hozumi
15:00 1) Present status of researches on differentiating agents.
Discussion (30 min)
Dr. A. Bloch (Roswell Park Memorial Institute)
15:30 2) New approaches to chemotherapy of myeloid leukemia by inducers of terminal differentiation of leukemia cells.
Discussion (30 min)
Dr. M. Hozumi (Saitama Cancer Center)
16:00 Adjourn
19:00-21:00 Reception at Wei Shing How* (Chinese restaurant, buffet-style)
All participants and observers are invited.
*) Wei Shing How: In front of the entrance of the Hotel New Otani’s tower. Tel. 261-2213

Friday, February 10
(9:30) 1) Interferon:
Chairpersons: Dr. Fujii & Dr. Kataoka
9:30 a) Current interferon researches in U.S.
Discussion (25 min)
Dr. R. Herberman (DCT, NCI)
9:55 b) Therapeutic contribution of anticellular and host T cell-dependent effects of interferon in Meth-A-bearing mice.
Discussion (20 min )
Dr. T. Kataoka (Cancer Chemotherapy Center)
10:15 c) Clinical trials of interferons for renal cell carcinoma in Japan.
Discussion (20 min)
Dr. Y. Ariyoshi (Aichi Cancer Center)
10:35 Coffee Break (15 min)
10:50 d) Phase II study of human lymphoblastoid interferon in hematological malignancies.
Discussion (20 min )
Dr. K. Yamada (Nagoya University)
(11:10) 2) Monoclonal Antibodies:
Chairpersons: Dr. Herberman & Dr. Ota
11:10 a) Monoclonal antibody researches in U. S.
Discussion (25 min)
Dr. H. Oettgen (Memorial Sloan-Kettering Institute )
11:35 b) Serological typing with monoclonal antibodies for classification of hematopoietic tumors.
Discussion (25 min)
Dr. R. Ueda (Aichi Cancer Center)
12:00 -13:00 Lunch (Rm. 906)
(13:00-16:30) V. VARIOUS NEW DRUGS
Chairpersons: Dr. Friedman & Dr. Taguchi
13:00 1) PL-AC:
a) Palmitoyl cytosine arabinoside (PL-AO) as a new antitumor agent by oral use.
Discussion (15 min)
Dr. T. Tsuruo (Cancer Chemotherapy Center)
13:15 b) Phase I-II study of palmitoyl cytosine arabinoside.
Discussion (15 min)
Dr. K. Yamada (Nagoya University)
13:30 2) M-83: 7-N-(p-hydroxyphenyl)- mitomycin C.
Discussion (20 min)
Dr. T. Taguchi (Osaka University)
13:50 3) SM-108: Current studies on a new imidazole derivative, SM-108.
Discussion (20 min)
Dr. S. Tsukagoshi (Cancer Chemotherapy Center)
14:10 4)!!!-OHP: Experimental antitumor activity of a new platinum complex,!!!-OHP.
Discussion (20 min )
Dr. T. Tashiro (Cancer Chemotherapy Center)
14:30 Coffee Break (15 min)
14:45 5) CBDCA, CHIP, TNO-6
Discussion (25 min)
Dr. M. Friedman (DCT, NCI)
Chairpersons: Dr. Wolpert & Dr. Tsukagoshi
15:10 6) Mitoxantrone:
a) Preliminary clinical study of mitoxantrone.
Discussion (15 min)
Dr. M. Ogawa (Cancer Chemotherapy Center)
15:25 b) Clinical study of mitoxantrone in U.S.
Discussion (15 min)
Dr. M. Friedman (DCT, NCI)
15:40 7) THP-ADM: Pharmacokinetics and clinical data of THP-adriamycin.
Discussion (20 min)
Dr. H. Majima (Chiba Cancer Center)
16:00 8) Other current new drugs in U.S.: Homoharringtonine, N-methylfor-mate, and Fludarbine phosphate.
Discussion (30 min)
Dr. M. Friedman (DCT, NCI)
16:30 Break (10 min)
Chairpersons: Dr. Schepartz & Dr. Ogawa
16:40 1) Current results on advanced gastric cancer in Japan. (15 min) Dr. M. Ogawa (Cancer Chemotherapy Center)
16:55 2) Gastric cancer in U.S. (15 min) Dr. M. Friedman (DCT, NCI)
17:10 General Discussion (15 min)
17:25 Summary and Closing Remarks Dr. S. Schepartz (DCT, NCI)
17:40 Adjourn