Second‐line mitoxantrone, etoposide, and cytarabine for acute myeloid leukemia: A single‐center experience

Abstract

The majority of patients with acute myeloid leukemia (AML) will require second-line chemotherapy for either relapsed or refractory disease. Currently, only allogeneic hematopoietic cell transplantation (HCT) offers a curative option in this setting and no preferred regimen has been established. The reported efficacy of second-line regimens is widely disparate, thus limiting informed clinical decision making. A retrospective review of 77 patients receiving therapy between 2001 and 2008 with relapsed, 42, and refractory, 35, AML was performed to determine overall response rate and survival following mitoxantrone (8 mg/m 2 /day), etoposide (100 mg/m 2 /day), and cytarabine (1,000 mg/m 2 /day) chemotherapy administered over 5 days. Among 77 patients (median age of 54 years and 64% intermediate risk karyotype) with median follow-up of 153 days, 18% achieved a complete response and 8% a morphologic leukemia-free state. Fifty-seven (74%) experienced treatment failure, 10 of whom achieved a remission after additional therapy. Median overall survival (OS) was 6.8 months. Among patients achieving a response, 50% received consolidation with allogeneic HCT, autologous HCT (5%), or consolidation chemotherapy alone (45%). A nonsignificant trend in overall response (50%, 27%, and 23.8%) and median OS (8.3, 6.8, and 4.7 months) was observed by cytogenetic stratification into favorable, intermediate, and unfavorable risk. Patients with refractory versus relapsed disease had similar overall responses (20% and 31%, P 5 0.41) and median OS (5.3 and 7.6 months, P 5 0.36). Despite risk stratification by the European Prognostic Index, our series demonstrates inferior rates of response and survival, illustrating the limited activity of this regimen in our cohort. Am. J. Hematol. 85:877-881, 2010. V V C 2010 Wiley-Liss, Inc. IntroductionAlthough intensive induction chemotherapy is effective in inducing a complete response (CR) in 50-80% of young (<60 years old) patients with acute myeloid leukemia (AML), the majority obtaining a CR eventually relapse and subsequently succumb to their disease [1][2][3]. Allogeneic hematopoietic cell transplantation (HCT) is generally accepted as the only curative approach for relapsed or refractory disease [4]. However, second-line HCT is limited by availability of an appropriately matched donor as well as transplant-related morbidity and mortality particularly among older or heavily pretreated patients.Second-line chemotherapy regimens including mitoxantrone, etoposide, and cytarabine (MEC) have been commonly used to obtain disease control preceding HCT or as primary treatment for relapsed disease among patients not eligible for HCT [5]. When first introduced in 1991, the CR rate following second-line MEC was reported at 61-66% with 4-5-month median overall survival (OS) [5,6]. However, in two recent phase III randomized trials, the response rates in the placebo arm to a single cycle of second-line MEC were only 19 and 28%, although OS was similar to the earlier studies, 5.4 and 5.2 months [7,8]. Becaus...

Efficacy of the hypomethylating agents as frontline, salvage, or consolidation therapy in adults with acute myeloid leukemia (AML)

“…In our study 27/28 patients were treated with decitabine, thus, the difference in response rate may reflect the differential activity of the two agents in this setting. The median overall survival also compares well with published cytotoxic salvage regimens in AML, [27–28] however the lack of marrow response suggests this strategy is suboptimal in patients for whom a reduced intensity allogeneic hematopoietic stem cell transplant (HSCT) is planned. Based on these data, hypomethylating agents, decitabine in particular, should be considered as salvage therapy for those patients who do not have the possibility of a HSCT.…”

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

“…Salvage reinduction therapy in AML achieves complete remission (CR) in only about one third of patients [1,2,4,5,6]. In subjects who are suitable candidates and have achieved CR after salvage therapy, the ultimate treatment goal is to perform allogeneic hematopoietic stem cell transplantation (HSCT) - the only potentially curative therapy for relapsed/refractory AML.…”

Podophyllotoxin derivatives: a patent review (2012 – 2014)

“…More specifically, it was a second line agent to treat acute myeloid leukemia. In addition, it was also used in combination with other chemotherapeutic drugs for the treatment of various types of tumors including testicular, small-cell lung cancers, lymphoma, leukemia, Kaposi's sarcoma and several carcinomas [13]. However, its continuous use leads to several adverse effects including myelo suppression, acquired drug resistance, cytotoxicity toward normal cells, etc.…”

“…Even though early clinical investigations carried out on several compounds such as TOP-53 (7), GL331 (8), NK611 (9), and tafluposide (F-11782, 11) indicated dose-limiting toxicities or lack of efficacy, medicinal chemists continued to pay a large interest to this class of compounds. As a result, three newer compounds namely QS-ZYX-1-61 (10), F-14512 (12) and Adva-27a (13) have been identified with superior antitumor efficacy than etoposide. The growing interest in this structure could be attributed to its anticancer potential and use in folklore medicine [29].…”