Enhanced Incorporation of 1-β-D-Arabinofuranosylcytosine by Pretreatment with Etoposide

Ooi, Kazuya; Ohkubo, Toshiki; Kuwabara, Hiroshi; Higashigawa, Masamune; Kawasaki, Hajime; Kakitoh, Hideshi; Kagawa, Yoshiyuki; Inagaki, Shoji; Sumida, Katsumi; Sakurai, Minoru

doi:10.3109/07357909309018870

Cited by 10 publications

(4 citation statements)

References 7 publications

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“…Since cytarabine is an analog of deoxycyctidine, etoposide may influence membrane transport and significantly influence the antitumor effect of etoposide and cytarabine when these drugs are administered in combination. In preclinical studies, etoposide has shown synergistic activity with cytarabine in leukemia cell lines, and the effect of the combination was found to be sequence dependent, with the maximum antileukemic effect observed when etoposide was given 6 h prior to cytarabine infusion [12,13,14,15]. …”

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confidence: 99%

The Combination of Fludarabine, Cytarabine and Etoposide Is an Active and Well-Tolerated Regimen in Relapsed/Refractory Acute Myeloid Leukemia

Aldoss

Haider

et al. 2013

Acta Haematol

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We retrospectively reviewed the outcome of 20 consecutive subjects with refractory/relapsed acute myeloid leukemia (AML; 9 refractory and 11 relapsed) treated at our institution with a fludarabine, cytarabine and etoposide (FCE) salvage regimen. Of 20 patients with refractory/relapsed AML, 15 (75%) achieved complete remission (CR)/CR with incomplete peripheral blood count recovery (CRi), including 14 CR and 1 CRi. The 4- and 8-week treatment-related mortality (TRM) for all patients during reinduction was 0 and 5%, respectively. Eight of 15 patients (53%) who successfully achieved CR were able to undergo allogeneic hematopoietic stem cell transplantation with a 0% non-relapse mortality rate. FCE is a new, well-tolerated, anthracycline-free regimen, which has a promising activity in relapsed/refractory AML and is associated with low TRM in this high-risk population.

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confidence: 99%

The Combination of Fludarabine, Cytarabine and Etoposide Is an Active and Well-Tolerated Regimen in Relapsed/Refractory Acute Myeloid Leukemia

Aldoss

Haider

et al. 2013

Acta Haematol

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“…As to the effect of this combination, a sequence-dependent antitumor effect was observed, and administration of EP 6 h before ara-C injection generated the best therapeutic results [28]. Ooi et al [29] demonstrated that the amount of ara-C incorporation into DNA of L1210 cells was increased to more than 200% of the control by a 3-and 6-h pre-administration of EP. They surmised that the period of repair of DNA damage by EP might be the critical time in which ara-C incorporation into DNA is increased.…”

Section: Discussionmentioning

confidence: 96%

The value of oral cytarabine ocfosfate and etoposide in the treatment of refractory and elderly AML patients

et al. 2008

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Twenty-one acute myeloid leukemia (AML) patients were enrolled and received oral induction therapy with cytarabine ocfosfate (SPAC) and etoposide (EP). The median age was 69 years (range: 33-86). There were 11 patients with de novo AML and 10 AML cases that had evolved from myelodysplastic syndromes. Seventeen patients had abnormal karyotypes including eight complex abnormalities, various complications, and 7 of 21 had a poor performance status (PS) with Eastern Cooperative Oncology Group (ECOG) scores of 3-4. All patients completed induction therapy without severe adverse events. Seven achieved complete remission (CR), and two achieved partial remission (PR). Uni- and multivariate analyses demonstrated a positive and significant correlation between the results of therapy (CR +/- PR) and overall survival. The plasma concentrations of cytosine arabinoside (ara-C) in some cases were higher than those previously reported, indicating the accumulation of ara-C with increasing numbers of days of SPAC administration. We conclude that this therapy is well tolerated and useful for refractory and elderly AML patients.

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“…A number of cytotoxic drugs, such as etoposide, cladribrine, araC, fludarabine and clofarabine have been found to stimulate dCK activity in human and murine leukemic cells [80,81]. It is important to notice that this stimulation requires a basal dCK level in the cells, because in NA-resistant and dCKdeficient cells there was no stimulation of the enzyme (unpublished data from Galmarini).…”

Section: Kinase Deficiencymentioning

confidence: 95%

Substrate cycles and drug resistance to 1-beta-D-arabinofuranosylcytosine (araC)

Fernández-Calotti

Jordheim

Giordano

et al. 2005

Leukemia & Lymphoma

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Acute myelogenous leukemia (AML) is the most common form of acute leukemia in adults. After diagnosis, patients with AML are mainly treated with standard induction chemotherapy combining cytarabine (araC) and anthracyclines. The majority of them achieve complete remission (CR) (65-80%). However, prospects for long-term survival are poor for the majority of patients. Resistance to chemotherapy therefore remains a major obstacle in the effective treatment of patients with AML. In this review, we highlight the current knowledge of substrate cycles involved in normal deoxynucleoside triphosphate (dNTPs) metabolism and their possible role in drug resistance to araC.

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Enhanced Incorporation of 1-β-D-Arabinofuranosylcytosine by Pretreatment with Etoposide

Cited by 10 publications

References 7 publications

The Combination of Fludarabine, Cytarabine and Etoposide Is an Active and Well-Tolerated Regimen in Relapsed/Refractory Acute Myeloid Leukemia

The Combination of Fludarabine, Cytarabine and Etoposide Is an Active and Well-Tolerated Regimen in Relapsed/Refractory Acute Myeloid Leukemia

The value of oral cytarabine ocfosfate and etoposide in the treatment of refractory and elderly AML patients

Substrate cycles and drug resistance to 1-beta-D-arabinofuranosylcytosine (araC)

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