Phase II study: treatment of non-Hodgkin's lymphoma with an oral antitumor derivative of bis(2,6-dioxopiperazine).

Abstract

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.

• Authors: R Ohno, K Yamada, M Hirano, S Shirakawa, M Tanaka, T Oguri, Y Kodera, Y Mitomo, Y Ikeda, S Yokomaku
• Journal: Journal of the National Cancer Institute (J Natl Cancer Inst) Vol. 84 Issue 6 Pg. 435-8 (Mar 18 1992) ISSN: 0027-8874 [Print] United States
• PMID: 1538420 (Publication Type: Clinical Trial, Journal Article)

Chemical References

• Antineoplastic Agents
• Piperazines
• sobuzoxane

Topics

• Administration, Oral
• Adolescent
• Adult
• Aged
• Aged, 80 and over
• Antineoplastic Agents (adverse effects, therapeutic use)
• Drug Evaluation
• Female
• Humans
• Lymphoma, Non-Hodgkin (drug therapy)
• Male
• Middle Aged
• Piperazines (adverse effects, therapeutic use)