Sequentially administered 5-azacitidine and amsacrine in refractory adult acute leukemia: a phase I-II trial of the Southeastern Cancer Study Group.
The Southeastern Cancer Study Group conducted a phase I-II trial of sequentially administered 5-azacitidine and amsacrine in patients with refractory adult acute leukemia from September 1980 to March 1983. The 5-azacitidine was administered by continuous iv infusion on Days 1-4 at doses ranging from 112 to 200 mg/m2/day, while amsacrine was given at doses ranging from 75 to 150 mg/m2/day on Days 5-8. The doses of 5-azacitidine and amsacrine were alternately escalated through six dose levels during the phase I portion of the trial. Of 128 patients entered, 102 (80%) were evaluable for response. Remission was achieved in 13 of 80 evaluable patients with acute myeloid leukemia, in one of 12 evaluable patients with acute lymphoid leukemia, and in none of 11 patients with blastic transformation of chronic granulocytic leukemia. Three remissions occurred in patients with acute myeloid leukemia who were refractory to initial induction chemotherapy with cytarabine and anthracycline combination chemotherapy. Remissions were relatively durable, lasting a median of 28 weeks in the 13 patients with refractory acute myeloid leukemia (range, 14-54 weeks). Toxic effects included universal severe myelosuppression, hyperbilirubinemia at a frequency and severity similar to those seen with amsacrine used as a single agent, moderately severe stomatitis and diarrhea, three incidents of amsacrine-related cardiac dysrhythmia, and a single case of probable drug-related cardiomyopathy. This combination has activity in the treatment of myeloid leukemia, which is primarily resistant to cytarabine and anthracyclines, and could have a role in primary management.
Winton
E F
EF
Hearn
E B
EB
Martelo
O
O
Presant
C A
CA
Adler
S
S
Vogler
W R
WR
Raney
M
M
Logan
T
T
Silberman
H M
HM
Omura
G A
GA
D000293:Adolescent; D000328:Adult; D000368:Aged; D000609:Aminoacridines / Q000008:administration & dosage; D000677:Amsacrine; D000970:Antineoplastic Agents / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000009:adverse effects; D001145:Arrhythmias, Cardiac / Q000139:chemically induced; D001374:Azacitidine / Q000008:administration & dosage; D004066:Digestive System Diseases / Q000139:chemically induced; D004334:Drug Administration Schedule; D004341:Drug Evaluation; D004351:Drug Resistance; D005260:Female; D006402:Hematologic Diseases / Q000139:chemically induced; D006801:Humans; D006932:Hyperbilirubinemia / Q000139:chemically induced; D007945:Leukemia, Lymphoid / Q000188:drug therapy*; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged
D000609:Aminoacridines; D000970:Antineoplastic Agents; D000677:Amsacrine; D001374:Azacitidine