A Phase II study of Bcl-2 antisense (oblimersen sodium) combined with gemtuzumab ozogamicin in older patients with acute myeloid leukemia in first relapse.
Oblimersen selectively targets Bcl-2 mRNA and has been shown to enhance the apoptotic activity of various antileukemic agents, including gemtuzumab ozogamicin (GO), in preclinical studies. We evaluated the efficacy and safety of oblimersen combined with GO in patients > or =60 years of age in first relapse with CD33+ acute myeloid leukemia. Oblimersen 7 mg/kg/day was given as a continuous intravenous infusion on days 1-7 and 15-21. GO 9 mg/m2 was given intravenously on days 4 and 18. Twelve of 48 patients (25%) achieved a major response (five, complete response and seven, complete response without platelet recovery). Ten of the 12 patients who achieved a major response survived >6 months compared with six of 36 non-responders. Serious adverse events for the oblimersen/GO combination were qualitatively similar to those reported for GO alone. Oblimersen can be safely combined with GO. Assessment of incremental benefit will require a randomized trial.
Moore
Joseph
J
Duke University Medical Center, Morris Cancer Clinics, P.O. Box 3872, Durham, NC 27710, United States. manusub@aol.com
Seiter
Karen
K
Kolitz
Jonathan
J
Stock
Wendy
W
Giles
Francis
F
Kalaycio
Matt
M
Zenk
David
D
Marcucci
Guido
G
D000208:Acute Disease; D000368:Aged; D000617:Aminoglycosides / Q000008:administration & dosage* / Q000009:adverse effects; D000911:Antibodies, Monoclonal / Q000008:administration & dosage* / Q000009:adverse effects; D061067:Antibodies, Monoclonal, Humanized; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D020732:Cytogenetic Analysis; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D064420:Drug-Related Side Effects and Adverse Reactions; D005260:Female; D005500:Follow-Up Studies; D000079982:Gemtuzumab; D006801:Humans; D007262:Infusions, Intravenous; D007951:Leukemia, Myeloid / Q000175:diagnosis / Q000188:drug therapy* / Q000235:genetics; D008297:Male; D020714:Maximum Tolerated Dose; D012008:Recurrence; D012307:Risk Factors; D015996:Survival Rate; D013873:Thionucleotides / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use*; D016896:Treatment Outcome
D000617:Aminoglycosides; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D013873:Thionucleotides; C408162:oblimersen; D000079982:Gemtuzumab