The value of oral cytarabine ocfosfate and etoposide in the treatment of refractory and elderly AML patients
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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.
- Champlin R, Gale RP. Acute myelogenous leukemia: recent advances in therapy. Blood. 1987;69:1551–62.
- Estey EH. Treatment of relapsed and refractory acute myelogenous leukemia. Leukemia. 2000;14:476–9. CrossRef
- Liu Yin JA. Acute myeloid leukaemia in the elderly: biology and treatment. Br J Haematol. 1993;83:1–6.
- Mayer RJ, Davis RB, Schiffer CA et al. Intensive postremission chemotherapy in adults with acute myeloid leukemia. N Engl J Med. 1994;331:896–903. CrossRef
- Löwenberg B, Suciu S, Archimbaud E et al. Use of recombinant granulocyte-macrophage colony-stimulating factor during and after remission induction chemotherapy in patients aged 61 years and older with acute myeloid leukemia (AML): final report of AML-11, a phase III randomized study of the Leukemia Cooperative Group of European Organization for the Research and Treatment of Cancer (EORTC-LCG) and the Dutch Belgian Hemato-Oncology Cooperative Group (HOVON). Blood. 1997;90:2952–61.
- Bauer KS, Karp JE, Garimella TS, Wu S, Tan M, Ross DD. A phase I and pharmacologic study of idarubicine, cytarabine, etoposide, and the multidrug resistance protein (MDR1/Pgp) inhibitor PSC-833 in patients with refractory leukemia. Leuk Res. 2005;29:263–71. CrossRef
- Baccarani M, Zaccaria A, Bandini G, Cavazzini G, Fanin R, Tura S. Low dose arabinosyl cytosine for treatment of myelodysplastic syndromes and subacute myeloid leukemia. Leuk Res. 1983;7:539–45. CrossRef
- Hartmann F, Jacobs G, Gotto H, Schwamborn J, Pfreundschuh M. Cytosine arabinoside, idarubicin and divided dose etoposide for the treatment of acute myeloid leukemia in elderly patients. Leuk Lymphoma. 2001;42:347–55. CrossRef
- Kodama K, Morozumi M, Saitoh K, Kuninaka A, Yoshino H, Saneyoshi M. Antitumor activity and pharmacology of I-β-d-arabinofuranosylcytosine-5’-stearylphosphate: an orally active derivative of 1-β-d-Arabinofuranosylcytosine. Jpn J Cancer Res. 1989;80:679–85.
- Ueda T, Kamiya K, Urasaki Y et al. Clinical pharmacology of 1-β-d-arabinofuranosylcytosine-5’-stearylphosphate, an orally administered long-acting derivative of low-dose β-d-arabinofuranosylcytosine. Cancer Res. 1994;54:109–13.
- Bennet JM, Catovsky D, Daniel MT et al. Proposed revised criteria for the classification of acute myeloid leukemia. Ann Intern Med. 1985;103:620–9.
- Sato T, Morozumi M, Kodama K, Kuninaka A, Yoshino H. Sensitive radioimmunoassay for cytarabine and uracil arabinoside in plasma. Cancer Trea Rep. 1984;68:1357–66.
- Kawashiro T, Yamashita K, Zhao XJ et al. A study on the metabolism of etoposide and possible interactions with antitumor or supporting agents by human liver microsomes. J Pharmacol Exp Ther. 1998;286:1294–300.
- Ota K, Ogawa N. Randomized controlled study of chemoimmunotherapy with bestatin of acute nonlymphocytic leukemia in adults. Biomed Pharmacother. 1990;44:93–102. CrossRef
- Ossenkoppele GJ, Graveland WJ, Sonneveld P et al. The value of fludarabine in addition to ARA-C and G-CSF in the treatment of patients with high-risk myelodysplastic syndromes and AML in elderly patients. Blood. 2004;103:2908–13. CrossRef
- van der Holt B, Lowenberg B, Burnett AK et al. The value of the MDR1 reversal agent PSC-833 in addition to daunorubicin and cytarabine in the treatment of elderly patients with previously untreated acute myeloid leukemia (AML), in relation to MDR1 status at diagnosis. Blood. 2005;106:2646–54. CrossRef
- Fukuoka M, Miyazaki T, Yoshida Y et al. Phase 1 study of YNK 01 (1-β-d-arabinofuranosylcytosine-5’-stearylphosphate) (in Japanese, with English abstract). Jpn J Cancer Chemother. 1990;17:2213–9.
- Kreis W, Chaudhri F, Chan K et al. Pharmacokinetics of low-dose 1-β-d-arabinofuranosylcytosine given by continuous intravenous infusion over twenty-one days. Cancer Res. 1985;45:6498–501.
- Tatsumi N, Yamada K, Ohshima T et al. Phase II study of YNK01 (1-β-d-arabinofuranosylcytosine-5’-stearylphosphate) on hematological malignancy(in Japanese, with English abstract). Jpn J Cancer Chemother. 1990;17:2387–95.
- Ohno R, Tatsumi N, Hirano M et al. Treatment of Myelodysplastic syndromes with orally administrated-D-arabinofuranosylcytosine-5’-Stearylphosphate. Oncology. 1991;48:451–5.
- Okumura H, Yoshida T, Takamatsu H et al. Treatment of acute myeloid leukemia and myelodysplastic syndrome with orally administered cytarabine ocfosfate and granulocyte colony-stimulating factor. Int J Hematology. 1997;65:263–8. CrossRef
- Nakaya K, Chou S, Kaneko M, Nakamura Y. Topoisomerase inhibitors have potent differentiation-inducing activity for human and mouse myeloid leukemia cells. Jpn J Cancer Res. 1991;82:184–91.
- Edick MJ, Gajjar A, Mahmoud HH et al. Pharmacokinetics and pharmacodynamics of oral etoposide in children with relapsed or refractory acute lymphoblastic leukemia. J Clin Oncol. 2003;21:1340–6. CrossRef
- Ogata K, Yamada T, Ito T et al. Low-dose etoposide: a potential therapy for myelodysplastic syndromes. Brit J Haematol. 1992;82:354–7.
- Kuriya S, Murai K, Miyairi Y et al. A combination chemotherapy with low doses of cytarabine and etoposide for high risk myelodysplastic syndromes and their leukemic stage. Cancer. 1996;78:422–6. CrossRef
- Lazzarino M, Morra E, Alessandrino EP et al. Etoposide-cytarabine therapy for acute leukemia following myelodysplastic syndromes or secondary to treatment for malignant diseases. Hematologica. 1987;72:341–5.
- Rivera G, Avery T, Roberts D. Response of L1210 to combinations of cytosine arabinoside and VM-26 or VP16–213. Eur J Cancer. 1975;11:639–47.
- Ohkubo T, Higashigawa M, Kawasaki H et al. Sequence-dependent antitumor effect of VP-16 and 1-β-d-arabinofuranosylcytosine in L1210 ascites tumor. Eur J Cancer Clin Oncol. 1988;24:1823–8. CrossRef
- Ooi K, Ohkubo T, Kuwabata H et al. Enhanced incorporation of 1-β-d-arabinofuranosylcytosine by pretreatment with etoposide. Cancer Investigation. 1993;11:388–92. CrossRef
- Housset M, Daniel MT, Degos L. Small doses of ARA-C in the treatment of acute myeloid leukaemia: differentiation of myeloid leukaemia cells? Br J Haematol. 1982;51:125–9.
- Löwenberg B, Suciu S, Archimbaud E et al. Mitoxantrone versus daunorubicin in induction-consolidation chemotherapy-the value of low-dose cytarabine for maintenance of remission, and an assessment of prognostic factors in acute myeloid leukemia in the elderly: final report of the Leukemia Cooperative Group of the European Organization for the Research and Treatment of Cancer and the Dutch-Belgian Hemato-Oncology Cooperative Hovon group randomized phase III study AML-9. J Clin Oncol. 1998;16:872–81.
- Haferlach T, Kern W, Schoch C et al. A new prognostic score for patients with acute myeloid leukemia based on cytogenetics and early blast clearance in trials of the German AML Cooperative Group. Haematologica. 2004;89:408–18.
- Schlenk RF, Frohling S, Hartmann F et al. Phase III study of all-trans retinoic acid in previously untreated patients 61 years or older with acute myeloid leukemia. Leukemia. 2004;18:1798–803. CrossRef
- The value of oral cytarabine ocfosfate and etoposide in the treatment of refractory and elderly AML patients
International Journal of Hematology
Volume 87, Issue 2 , pp 118-125
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- Springer Japan
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- Cytarabine ocfosfate
- Refractory acute myeloid leukemia
- Induction therapy
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