Phase II study of clofarabine monotherapy in previously untreated older adults with acute myeloid leukemia and unfavorable prognostic factors.
OBJECTIVE
This phase II study assessed clofarabine monotherapy in older adults (>or= 60 years of age) with untreated acute myeloid leukemia (AML) and at least one unfavorable baseline prognostic factor.


METHODS
Clofarabine was administered intravenously for 5 days at 30 mg/m(2)/d during induction and 20 mg/m(2)/d during reinduction/consolidation (six cycles maximum). The primary end point was overall remission rate (ORR; ie, complete remission [CR] plus CR with incomplete platelet recovery [CRp]).


RESULTS
In 112 evaluable patients who were treated (median age, 71 years; range, 60 to 88 years), the ORR was 46% (38% CR, 8% CRp). ORR by unfavorable prognostic factor was 39% for patients >or= 70 years of age; 32% for Eastern Cooperative Oncology Group (ECOG) performance status 2; 51% for antecedent hematologic disorder; 54% for intermediate karyotype; 42% for unfavorable karyotype; and 48%, 51%, and 38% for one, two, and three risk factors, respectively. The median disease-free survival was 37 weeks (95% CI, 26 to 56 weeks). Median duration of remission was 56 weeks (95% CI, 33 to not estimable). The estimated median overall survival was 41 weeks (95% CI, 28 to 53 weeks) for all patients, 59 weeks for patients with CR/CRp, and 72 weeks for patients with CR. The 30-day all-cause mortality was 9.8%. The most common non-laboratory drug-related toxicities (>or= 20% patients) were nausea, febrile neutropenia, vomiting, diarrhea, rash, and fatigue.


CONCLUSIONS
Clofarabine is an active agent with acceptable toxicity in patients age 60 years or older with untreated AML who have at least one unfavorable prognostic factor. ORR did not seem affected by the presence of multiple unfavorable prognostic factors.
Kantarjian
Hagop M
HM
University of Texas M. D. Anderson Cancer Center, Houston, TX 77030, USA. hkantarj@mdanderson.org
Erba
Harry P
HP
Claxton
David
D
Arellano
Martha
M
Lyons
Roger M
RM
Kovascovics
Tibor
T
Gabrilove
Janice
J
Craig
Michael
M
Douer
Dan
D
Maris
Michael
M
Petersdorf
Stephen
S
Shami
Paul J
PJ
Yeager
Andrew M
AM
Eckert
Stephen
S
Abichandani
Rekha
R
Faderl
Stefan
S
D000227:Adenine Nucleotides / Q000627:therapeutic use*; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001087:Arabinonucleosides / Q000627:therapeutic use*; D000077866:Clofarabine; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D009367:Neoplasm Staging; D011379:Prognosis; D011446:Prospective Studies; D012074:Remission Induction; D015996:Survival Rate; D016896:Treatment Outcome
D000227:Adenine Nucleotides; D000970:Antineoplastic Agents; D001087:Arabinonucleosides; D000077866:Clofarabine