| Title | Combination of cladribine plus topotecan for recurrent or refractory pediatric acute myeloid leukemia. | | Author(s) | Inaba H, Stewart CF, Crews KR, Yang S, Pounds S, Pui CH, Rubnitz JE, Razzouk BI, Ribeiro RC | | Institution | Department of Oncology, St. Jude Children's Research Hospital, Memphis, Tennessee. | | Source | Cancer 2009 Nov 2. | | Abstract | BACKGROUND:: The prognosis after recurrence of pediatric acute myeloid leukemia (AML) is poor, and effective salvage regimens are urgently needed.
METHODS:: In phase 1 and pilot studies, the authors evaluated the maximum tolerated dose (MTD) and dose-limiting toxicities (DLTs) of a 5-day course of cladribine followed by topotecan in pediatric patients with recurrent/refractory AML. The cladribine dose was escalated as follows: 9.1, 13.6, 16.3, and 19.5 mg/m(2) per day (8.9 mg/m(2) per day in the pilot study). Outcome was analyzed according to the absence (Stratum 1) versus presence (Stratum 2) of previous allogeneic hematopoietic stem cell transplantation. Twenty-six patients (20 in Stratum 1 and 6 in Stratum 2) were treated.
RESULTS:: The MTD was not reached in Stratum 1, but a DLT occurred at the lowest cladribine dosage (9.1 mg/m(2) per day) in Stratum 2. Febrile neutropenia was common in both strata. Nine (34.6%) of 26 patients experienced a complete response, and 7 (30.4%) achieved a partial response; 5 (19.2%) were long-term survivors at the time of last follow-up. Clinical outcome was not associated with cladribine or topotecan systemic exposure.
CONCLUSIONS:: The combination was well tolerated in Sratum 1, and the response rate was encouraging. This regimen offers a postrecurrence treatment alternative for patients, especially those who have received anthracycline-containing chemotherapy. Cancer 2009. (c) 2009 American Cancer Society. | | Language | ENG | | Pub Type(s) | JOURNAL ARTICLE
| | PubMed ID | 19885837 |
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