Developmental Therapeutics and Medical Oncology

　Introduction

　　The Division of Oncology and Hematology has been managing many kinds of malignancies. Breast cancer, malignant lymphoma, head and neck cancers, lung cancer and primary unknown carcinoma are major disease specific targets. Our clinical and research activities are mainly focused on the following five fields:
1.　Development of newly synthesized anticancer agents through phase I trails,
2.　Disease oriented clinical trials, especially for breast cancer, head and neck cancers, malignant lymphomas and hematological malignancies,
3.　High dose chemotherapy with autologous bone marrow transplantation (BMT) and/or peripheral blood stem cell support in an experimental setting,
4.　Standard chemotherapy treatment as clinical practice,
5.　Palliative care for terminal stage patients.
In addition, the number of protocols for developmental therapeutics has been rapidly increasing.

　Routine Activities

　　We managed many kinds of malignant disease in the past year including breast cancer, non-Hodgkin's lymphoma, Hodgkin disease, acute leukemia, lung cancer, colorectal cancer, pharyngeal and laryngeal cancers, pancreatic cancers, soft tissue sarcomas, uterine cancer, ovarian cancer as well as primary unknown adenocarcinoma. For diseases with established standard chemotherapy and without phase III clinical trial project, routine chemotherapy was administered as clinical practice. Experimental therapeutics was conducted for patients without standard treatment or who failed standard chemotherapy.

　Research Activities

　　The following clinical trials were conducted in 1998.
Phase I Trials
　　UCN-01
　　TOP-53
　　DX-8951f
Phase I/II Trial
　　Nedaplatin + 5FU (head and neck cancer)
　　Docetaxel+ADR (breast cancer)
Phase II Trials
　　SMS201-995
　　JM-216 for breast cancer
Phase III Trials
　　JCOG (Japan Clinical Oncology Group) breast cancer trials
　　JALSG (Japan Acute Leukemia Study Group) for leukemia
　　JCOG (Japan Clinical Oncology Group) lymphoma study

Short descriptions of the three phase I clinical trials: UCN-01
　　Clinical development of the new proteinkinase C inhibitor UCN-01 was conducted both by the National Cancer Center of Japan and by the National Cancer Institute of the U.S. Although the administration schedule in our phase I study is a 3-hour infusion, which is different from the 71-hour infusion in the U.S. study, exchange of clinical information is very informative. The final administration schedule will be decided on the basis of two phase I trials.

TOP-53
　　We have developed a new dose escalation strategy for anticancer agents through the TOP-53 project. To minimize the number of patients who are given non-effective doses and non-toxic doses by escalation methodologies (pharmacokinetically guided dose escalation and continual reassessment method) was combined. Finally the number of dose escalation steps were treated near maximum tolerated doses. This paper was presented at an oral session of the American Society of Clinical Oncology annual meeting in 1998.

DX8951f
　　The phase I study of the new camptothecin derivative DX-8951f has been conducted by an international development strategy. A total of 8 phase I protocols were simultaneously instituted in Europe, the U.S., and Japan. We administered an intermittent intra venous infusion over 30 minutes every 3 weeks, a schedule that is identical to the phase I study conducted in France. Our finding of a maximum tolerated dose (MTD) similar to the MTD in the French study suggested that there are no pharmacokinetic or pharmacodynamic differences between the French and Japanese population.

　Statistics

Protocols and Number
of Patients Attended

Protocol	Pts
UCN-01	3
TOP-53	12
DX-8951f	9
254S+CDDP	6
Docetaxel+ADR	3
SMS201-995	2
JM-216	10

(Y. Sasaki)　

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