Hematology & Oncology

Research Activities/Investigational Drug Development

1) Phase I studies of novel drugs

Phase I studies of new anticancer agents are conducted in collaboration with pharmaceutical companies. These include both cytotoxic and molecular target drugs. Phase I studies of LY317615 (a PKC inhibitor) and vinflunine (a vinca alkaloid) were completed in 2007. Patients are being enrolled in phase I studies of E7389 (a synthetic analog of Halichondrin B), ABI-007 (a cremophor-free albumin-bound paclitaxel), AG- 013736 (an inhibitor of VEGF receptor tyrosine kinases), and LBQ707 (an oral campthothecin derivative).

2) Phase I/II studies of new chemotherapeutic combinations

In contrast to the above phase I studies that are in a very early stage of clinical development and enroll patients with various cancers, clinical studies on specific disease targets are also underway. After the phase I/II studies of oral fludarabine for patients with low-grade lymphoma, a phase II study for evaluation of the efficacy and safety of combined oral fludarabine and rituximab was completed in 2007.
For patients with recurrent chemosensitive malignant lymphomas, a phase I study is being conducted to evaluate the efficacy and toxicity of combination chemotherapy with ranimustine, etoposide, cytarabine, and melphalan (MEAM) as a conditioning regimen for autologous stem cell transplantation. A dose-finding study is being conducted on an oral combination of cyclophosphamide, etoposide, and procarbazine (CEP) for treating the first relapse of aggressive lymphoma in more elderly patients.

3) Phase II/III studies

An international phase III study of denosumab (a humanized monoclonal antibody for RANKL), is being conducted on patients with metastatic breast cancer in order to compare its activity in preventing skeletal-related events with that of zoledronate. We are also participating in an international phase III trial of adjuvant trastuzumab therapy with or without lapatinib (a quinazoline derivative with EGFR and HER-2 inhibitory activity) in patients with HER-2 overexpressed breast cancer (ALTTO). A prospective randomized study of taxane (paclitaxel or docetaxel) versus TS-1 as a front-line chemotherapy is also in progress to select an effective chemotherapeutic regimen (SELECT-BC) for patients with metastatic breast cancer in whom hormone therapy has failed and trastuzumab is not indicated. In addition, a multicenter phase II study of avastin combined with paclitaxel for patients with HER-2 negative breast cancer has been initiated in 2007.

4) Pharmacological studies

Pharmacokinetic analysis is performed to develop better strategies for the administration of anticancer agents. In a phase I study of MEAM for treatment of recurrent chemosensitive malignant lymphomas, the pharmacokinetics of ranimustine are being investigated. For evaluation of the bioavailability of oral etoposide administered with or without green tea, the pharmacokinetics of etoposide and catechin—the major component of green tea—are under investigation in patients with various cancers who are treated with oral etoposide in clinical practice.

● K. Itoh ●

Number of participants in the clinical trials
  Number of patients
Phase I trials  
　　LY317615 17
　　Vinflunine 9
　　E7389 15
　　ABI-007 6
　　LBQ707 19
　　AG-013736 12
Phase I/II trials  
　　oral fludarabine and rituximab 6
　　MEAM 6
　　CEP 7
Phase II/III trials  
　　SELECT-BC 16
　　Denosumab 4
Total 117

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