Remission induction therapy of untreated acute myeloid leukemia using a non-cytarabine-containing regimen of idarubicin, etoposide, and carboplatin.
BACKGROUND
The safety and efficacy of idarubicin, etoposide, and carboplatin as remission induction therapy for patients younger than 60 years with untreated acute myeloid leukemia was studied as an alternative to standard regimens based on cytarabine plus anthracycline.


METHODS
Eligible patients received idarubicin (36-40 mg/m2), etoposide (500 mg/m2), and carboplatin (1000-1500 mg/m2) over 5 days. Those who achieved complete remission received a single course of cytarabine 1.5 gm/m2 every 12 hours for a total of 12 doses. D-xylose absorption was studied as a marker for cytotoxic therapy-induced gut mucosal damage. Cytogenetic and immunophenotyping studies were performed at the time of diagnosis and examined for prognostic importance.


RESULTS
Remission was achieved in 29 (67%) of 43 patients with a single induction course. The median leukemia free and overall survival times were 15.4 months (95% CI 6.5-24.2) and 12.5 months (95% CI 5.9-19.1), respectively. Induction mortality was 14%. Karyotype (normal, simple, or complex vs. very complex) was the strongest predictor of remission (79% vs. 25%, P=0.01), leukemia free survival (odds ratio [OR] 19.3, 95% CI 2.7-138.9), and overall survival (OR 5.4, 95% CI 2.1-13.9). Dose-limiting gut mucosal toxicity was greatest during Weeks 2 and 3. Bloodstream infections occurred in 49% of patients at a median of 12 days. Grade 3-4 diarrhea, nausea, stomatitis, esophagitis/dysphagia, and vomiting developed in 33%, 26%, 23%, 9%, and 2% of cases, respectively, at a median of 17, 16, 11, 15.5, and 21 days, respectively.


CONCLUSIONS
This regimen was active in adults younger than 60 years with untreated acute myeloid leukemia and normal, simple, or complex karyotypes. Remission duration was confounded by karyotype. Mucosal toxicity limited the tolerability of this regimen. These adverse effects might be overcome by increasing the intensity of postremission therapy and modifying the dosing schedule.
Department of Medicine, University of Manitoba, the Health Sciences Centre, Winnipeg, Canada.
E J
EJ
Bow
G
G
Gallant
G J
GJ
Williams
D
D
Woloschuk
T B
TB
Shore
M
M
Rubinger
B A
BA
Schacter
D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D016190:Carboplatin / Q000008:administration & dosage; D018572:Disease-Free Survival; D004361:Drug Tolerance; D005047:Etoposide / Q000008:administration & dosage; D005260:Female; D006801:Humans; D015255:Idarubicin / Q000008:administration & dosage; D007413:Intestinal Mucosa / Q000187:drug effects; D007951:Leukemia, Myeloid / Q000188:drug therapy* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D012074:Remission Induction; D015996:Survival Rate; D016896:Treatment Outcome; D014994:Xylose
D000903:Antibiotics, Antineoplastic; D000972:Antineoplastic Agents, Phytogenic; D005047:Etoposide; D014994:Xylose; D016190:Carboplatin; D015255:Idarubicin