TY - JOUR
T1 - Phase I study of Irofulven (MGI 114), an acylfulvene illudin analog, in patients with acute leukemia
AU - Giles, Francis
AU - Cortes, Jorge
AU - Garcia-Manero, Guillermo
AU - Kornblau, Stephen
AU - Estey, Elihu
AU - Kwari, Monica
AU - Murgo, Anthony
AU - Kantarjian, Hagop
PY - 2001
Y1 - 2001
N2 - Irofulven (MGI 114, 6-hydroxymethylacylfulvene, HMAF) is a semisynthetic illudin analog with broad in vitro anti-neoplastic activity. In this leukemia phase I study, we investigated the toxicity profile and activity of Irofulven in patients with primary refractory or relapsed acute myeloid leukemia (AML), acute lymphocytic leukemia (ALL), or myelodysplastic syndromes (MDS). Irofulven was given as an intravenous infusion over five minutes daily for five days. The starting dose was 10 mg/m2/day (50 mg/m2/course). Courses were scheduled to be given every 3-4 weeks according to toxicity and antileukemic efficacy. Twenty patients {AML: 17 patients; MDS: one patient; ALL: one patient; mixed lineage acute leukemia: one patient} were treated. Nausea, vomiting, hepatic dysfunction, weakness, renal dysfunction, and pulmonary edema were dose limiting toxicities, occurring in two of five patients treated at 20 mg/m2/day and two of three patients treated at 12.5 mg/m2/day. The MTD was defined as 10mg/m2/day for five days. One patient with primary resistant AML achieved complete remission. Proposed phase II studies will further define the activity of Irofulven in patients with better prognosis AML and in other hematological malignancies, both as a single agent and in combination regimens, particularly with topoisomerase 1 inhibitors.
AB - Irofulven (MGI 114, 6-hydroxymethylacylfulvene, HMAF) is a semisynthetic illudin analog with broad in vitro anti-neoplastic activity. In this leukemia phase I study, we investigated the toxicity profile and activity of Irofulven in patients with primary refractory or relapsed acute myeloid leukemia (AML), acute lymphocytic leukemia (ALL), or myelodysplastic syndromes (MDS). Irofulven was given as an intravenous infusion over five minutes daily for five days. The starting dose was 10 mg/m2/day (50 mg/m2/course). Courses were scheduled to be given every 3-4 weeks according to toxicity and antileukemic efficacy. Twenty patients {AML: 17 patients; MDS: one patient; ALL: one patient; mixed lineage acute leukemia: one patient} were treated. Nausea, vomiting, hepatic dysfunction, weakness, renal dysfunction, and pulmonary edema were dose limiting toxicities, occurring in two of five patients treated at 20 mg/m2/day and two of three patients treated at 12.5 mg/m2/day. The MTD was defined as 10mg/m2/day for five days. One patient with primary resistant AML achieved complete remission. Proposed phase II studies will further define the activity of Irofulven in patients with better prognosis AML and in other hematological malignancies, both as a single agent and in combination regimens, particularly with topoisomerase 1 inhibitors.
KW - Acute leukemia
KW - Acylfulvene
KW - Illudins
KW - Irofulven
KW - MGI 114
KW - Phase I
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U2 - 10.1023/A:1006432012394
DO - 10.1023/A:1006432012394
M3 - Article
C2 - 11291829
AN - SCOPUS:0035096161
SN - 0167-6997
VL - 19
SP - 13
EP - 20
JO - Investigational New Drugs
JF - Investigational New Drugs
IS - 1
ER -