Clofarabine, cyclophosphamide and etoposide for the treatment of relapsed or resistant acute leukemia in pediatric patients

Abstract

Clofarabine is a promising new chemotherapeutic agent that is active in the treatment of pediatric acute leukemia. Forty children (16 with acute myeloid leukemia [AML], 24 with acute lymphoblastic leukemia [ALL]), aged 1-20 years (median 7.6 years) with relapsed or refractory ALL or AML were treated because of resistance to first-line treatment (n =5), or for first (n =22), second (n =11) or third relapse (n =2). They received clofarabine (40 mg/m(2)/day) associated with etoposide (100 mg/m(2)/day) and cyclophosphamide (440 mg/m(2)/day) administered as one or two induction cycles (5 days of chemotherapy) in an attempt to reach complete remission (CR) or CR without platelet recovery (CRp). This was followed by 1-3 consolidation cycles (4 days of chemotherapy) for a maximum of four cycles. Seven (44%) out of 16 and 10 (42%) out of 24 evaluable children with AML and ALL, respectively, responded to treatment. The most common adverse events were infections and gastrointestinal and hepatic toxicity. Thirteen (76%) out of 17 responders underwent hematopoietic stem cell transplant. The 24-month overall survival was 25%, while it was 59% among patients who responded to the first induction cycle. Our study suggests that this drug regimen is well tolerated and can be effective in heavily pretreated pediatric patients with relapsed or refractory acute leukemia.

Optimization of a clofarabine‐based drug combination regimen for the preclinical evaluation of pediatric acute lymphoblastic leukemia

“…Clofarabine is typically administered in combination with cyclophosphamide and etoposide, and this combination shows a synergistic effect in relapsed/refractory pediatric ALL patients . Therefore, we next assessed whether this CLO/ETO/CTX combination could be used in PDX models to better facilitate drug selection for patients.…”

Marine drug Haishengsu increases chemosensitivity to conventional chemotherapy and improves quality of life in patients with acute leukemia

“…The resistance of tumor cells to anticancer agents continues to be a problem that hinders successful chemotherapy. How to increase chemosensitivity in relapsed leukemia has become an important research objective [24,25].…”

Acute Lymphoblastic Leukemia, Version 2.2015

“…108 In subsequent, small phase II studies in pediatric patients (age 1-21 years) with relapsed/refractory ALL, this combination induced response rates (CR plus CRp) of 42% to 44%. 109,110 A multicenter retrospective study of data from pediatric patients treated with clofarabine outside of the clinical trial setting (n = 23; age 0-17 years) reported that among those treated with the combination of clofarabine, cyclophosphamide, and etoposide (n = 18), the CR rate was 56%. 111 The combination regimen of clofarabine, cyclophosphamide, and etoposide has been associated with prolonged and severe myelosuppression, febrile episodes or severe infections (including sepsis or septic shock), mucositis, and liver toxicities including fatal venoocclusive disease (the latter occurring in the postallogeneic HCT setting).…”

“…111 The combination regimen of clofarabine, cyclophosphamide, and etoposide has been associated with prolonged and severe myelosuppression, febrile episodes or severe infections (including sepsis or septic shock), mucositis, and liver toxicities including fatal venoocclusive disease (the latter occurring in the postallogeneic HCT setting). [109][110][111] Moreover, data are very limited with this combination regimen in adult patients with ALL. Because the use of this regimen requires close monitoring and intensive supportive care measures, patients should only be treated in centers with expertise in the management of ALL.…”