Research Activities

1) Phase I/II studies of new chemotherapeutic agents
Phase I or phase I/II studies of new anticancer agents for specific disease targets are conducted in collaboration with pharmaceutical companies. For patients with low-grade lymphoma and mantle cell lymphoma, a phase I study of RAD001 (an mTOR inhibitor) and a phase II study of SyBL-0501 (bendamustin) were completed in 2008. For patients with recurrent chemo- sensitive malignant lymphomas, a phase I study is currently 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. The recommended dose of an oral combination of cyclophosphamide, etoposide, and procarbazine (CEP) for the first relapse of aggressive lymphoma in more elderly patients has been determined and, consequently, a phase II study has been initiated. 2) Phase II/III studies
An international phase III study of denosumab (a humanized monoclonal antibody for RANKL) is presently being conducted on patients with metastatic breast cancer to compare its activity in preventing skeletal-related events with that of zoledronate. ALTTO, 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, is also currently being conducted. 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 2007, a multicenter phase II study of avastin combined with paclitaxel for patients with HER-2 negative breast cancer was also initiated. In addition, a phase II study of BMS-247550 (ixabepilone) is presently being conducted for patients with metastatic breast cancer who have been treated with anthoracycline and were refractory for taxane. 3) Pharmacological studies
Pharmacokinetic analysis is also performed to develop better strategies for the administration of anticancer agents. For the evaluation of the bioavailability of oral etoposide administered with or without green tea, the pharmacokinetics of etoposide and catechin, which is the major component of green tea, have been clarified in 25 patients with various cancers treated with oral etoposide in clinical practice.

● K. Itoh ●

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