Clinical activity of arsenic trioxide for the treatment of multiple myeloma

• Published in: Leukemia Vol. 16; no. 9; pp. 1835 - 1837
• Main Authors: MUNSHI, N. C, TRICOT, G, DESIKAN, R, BADROS, A, ZANGARI, M, TOOR, A, MORRIS, C, ANAISSIE, E, BARLOGIE, B
• Format: Journal Article
• Language: English
• Published: London Nature Publishing 01.09.2002; Nature Publishing Group
• Subjects: Acute promyeloid leukemia; Adult; Aged; Angiogenesis; Antineoplastic agents; Antineoplastic Agents - adverse effects; Antineoplastic Agents - therapeutic use; Apoptosis; Arsenic; Arsenic trioxide; Arsenicals - adverse effects; Arsenicals - therapeutic use; Biological and medical sciences; Cell differentiation; Chemical compounds; Chemotherapy; Complications; Differentiation (biology); Drug Evaluation; Health services; Humans; Leukemia; Medical sciences; Middle Aged; Multiple myeloma; Multiple Myeloma - drug therapy; Multiple Myeloma - pathology; Neoplasm Recurrence, Local - drug therapy; Neoplasm Recurrence, Local - pathology; Neutropenia - chemically induced; Oxides - adverse effects; Oxides - therapeutic use; Parasitic diseases; Patients; Pharmacology; Pharmacology. Drug treatments; Promyeloid leukemia; Salvage Therapy; Thromboembolism; Treatment Outcome; Tumors; Antineoplastic agent; Human; Immunopathology; Relapse; Treatment resistance; Intravenous administration; Toxicity; Treatment efficiency; Arsenic trioxide; Malignant hemopathy; Myeloma; Chemotherapy; Treatment; Immunoglobulinopathy; Lymphoproliferative syndrome; Phase II trial; Complication
• ISSN: 0887-6924; 1476-5551
• DOI: 10.1038/sj.leu.2402599

Arsenic has been used since ancient times as a therapeutic agent. However, until recently its use in modern medicine has been restricted to the treatment of a limited number of parasitic infections. In the early 1990s, reports from China described impressive results with arsenic trioxide in patients with de novo, relapsed, and refractory acute promyelocytic leukemia (APL). Other investigators subsequently confirmed these results leading to approval of its use for relapsed or refractory APL in the United States. Investigations of this agent have demonstrated that its efficacy in APL and preclinical tumor models is dependent upon a number of mechanisms, including induction of apoptosis, effects on cellular differentiation, cell cycling, and tumor angiogenesis. Subsequent preclinical studies showed significant activity of arsenic trioxide in multiple myeloma (MM). Based on this, in a phase II trial, we have evaluated the activity of arsenic trioxide in 14 patients with relapsed MM, refractory to conventional salvage therapy. With the dose and schedule used, treatment with arsenic trioxide produced responses in three patients and prolonged stable disease in a fourth patient, with the longest response lasting 6 weeks. Although treatment was reasonably well tolerated, in these patients with extensive prior therapy, 11 developed cytopenia, five associated with infectious complications and three developed deep vein thromboses. The results of this small trial support further investigation of this novel drug for the treatment of patients with relapsed or refractory MM.