Phase II study: treatment of non-Hodgkin's lymphoma with an oral antitumor derivative of bis(2,6-dioxopiperazine).
BACKGROUND: Although razoxane (ICRF-159), a derivative of bis(2,6-dioxopiperazine), has shown significant antitumor activity in several murine tumors, inadequate bioavailability has limited its clinical efficacy. Sobuzoxane (MST-16), another derivative of bis(2,6-dioxopiperazine), has shown activity against a broad spectrum of murine tumors and human tumor xenografts in nude mice and a lack of cross-resistance to vincristine, doxorubicin, cyclophosphamide, fluorouracil, etoposide, and mitomycin C. These findings suggest that MST-16 has a mode of cytocidal activity different from that of other antitumor agents. PURPOSE: The present late phase II study was conducted to evaluate the clinical efficacy and toxicity of MST-16 in non-Hodgkin's lymphoma (NHL). METHODS: As part of a multi-institutional cooperative study, we conducted a study of MST-16 in 27 patients with NHL who were assessable for drug efficacy and toxicity. MST-16, a bis(2,6-dioxopiperazine) analogue and an inhibitor of topoisomerase II, was administered orally at a dose of 1600 mg/m2 a day for 5-7 days at intervals of 2-3 weeks. RESULTS: Response consisted of one complete remission and seven partial remissions in 27 assessable patients. Response was achieved at a median of 13 days (range, 9-62 days) after initiation of therapy and lasted a median of 46 days (range, 29-155 days). Major toxic effects were leukopenia in 70% of the patients, thrombocytopenia in 44%, and gastrointestinal disorders in 37%. CONCLUSIONS: MST-16 was shown to be effective in NHL and deserves further clinical trial, since the drug shows little cross-resistance to available antitumor drugs. IMPLICATIONS: Phase II clinical studies of MST-16 in treatment of breast cancer, gastric cancer, and adult T-cell leukemia and lymphoma are also being conducted in Japan. Future trials of combination chemotherapy using MST-16 with other antitumor drugs are warranted in view of the additive effects observed in studies of MOLT-3 cells and studies of L1210 leukemia in mice.[1]References
- Phase II study: treatment of non-Hodgkin's lymphoma with an oral antitumor derivative of bis(2,6-dioxopiperazine). Ohno, R., Yamada, K., Hirano, M., Shirakawa, S., Tanaka, M., Oguri, T., Kodera, Y., Mitomo, Y., Ikeda, Y., Yokomaku, S. J. Natl. Cancer Inst. (1992) [Pubmed]
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