A new multidrug reinduction protocol with topotecan, vinorelbine, thiotepa, dexamethasone, and gemcitabine for relapsed or refractory acute leukemia

Kolb, E. Anders; Steinherz, Peter G.

doi:10.1038/sj.leu.2403097

Cited by 39 publications

(26 citation statements)

References 35 publications

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“…Despite various reports of the use of topotecan to treat ALL in adults, 12,13 very few have reported the use of topotecan as a single agent 9,11 or in multiagent therapy 29 in childhood ALL. In the current study, we confirmed that topotecan possesses considerable antileukemic activity against pediatric ALL by administering topotecan in an ''upfront window.''…”

Section: Discussionmentioning

confidence: 99%

Phase II study of topotecan in combination with dexamethasone, asparaginase, and vincristine in pediatric patients with acute lymphoblastic leukemia in first relapse

Hijiya

Stewart

Zhou

et al. 2008

Cancer

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BACKGROUND. The authors evaluated the response rate, toxicity, and pharmacokinetics of topotecan given before standard induction therapy for childhood acute lymphoblastic leukemia (ALL) in first relapse. METHODS. Patients received topotecan (2.4 mg/m2 daily as a 30‐minute infusion) for 5 days before induction therapy with dexamethasone, vincristine, and asparaginase (native or pegylated Escherichia coli). The pharmacokinetics of topotecan were measured with the first dose of treatment in 23 patients. RESULTS. Twenty‐eight of 31 patients with circulating blast cells were evaluable for response to topotecan. Twenty‐five patients (89.3%) had a response (>25% decrease in circulating blast cells). The leukocyte count (P = .0001) and blast cell count (P = .0009) declined significantly during topotecan therapy. The median (range) topotecan lactone area under the concentration‐time curve after the first dose was 85.4 L/hour/m2 (range, 38.7–229.3 L/hour/m2). At the end of induction, 23 patients (74.2%) had a complete response, 1 patient (3.2%) had a partial response, 5 patients (16.1%) had no response, and 2 patients had died of infection. Six of the 17 patients who were studied for minimal residual disease (MRD) achieved MRD‐negative status at the end of induction. The main toxicities were hematologic, gastrointestinal, and hepatic. The estimated 5‐year survival rate, event‐free survival rate, and cumulative incidence of second relapse were 24.1% ± 7.9%, 18.2% ± 7.4%, and 22.8% ± 8.7%, respectively, in the 29 patients who had a hematologic first relapse. CONCLUSIONS. A regimen comprising single‐agent topotecan given with a standard 3‐drug combination was effective in inducing remission in pediatric patients with relapsed ALL and was tolerated well. Cancer 2008. © 2008 American Cancer Society.

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Section: Discussionmentioning

confidence: 99%

Phase II study of topotecan in combination with dexamethasone, asparaginase, and vincristine in pediatric patients with acute lymphoblastic leukemia in first relapse

Hijiya

Stewart

Zhou

et al. 2008

Cancer

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“…Although clinical remission can be achieved in most relapses, long-term survival rates range from 40% to 50%. [11][12][13][14] Reinduction of patients with relapsed ALL commonly includes conventional agents largely identical to those used at initial diagnosis. Hematopoietic stem-cell transplantation (HSCT) is often used as consolidation therapy.…”

Section: Introductionmentioning

confidence: 99%

Outcome of Patients Treated for Relapsed or Refractory Acute Lymphoblastic Leukemia: A Therapeutic Advances in Childhood Leukemia Consortium Study

Barnette

et al. 2010

JCO

250

224

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A B S T R A C T PurposeDespite improvements in treatment, approximately 20% of patients with acute lymphoblastic leukemia (ALL) experience relapse and do poorly. The Therapeutic Advances in Childhood Leukemia (TACL) Consortium was assembled to assess novel drugs for children with resistant leukemia. We hypothesize that novel agents and combinations that fail to improve baseline complete remission rates in comparable populations are unlikely to contribute to better outcomes and should be abandoned. We sought to define response rates and disease-free survival (DFS) rates in patients treated at TACL institutions, which could serve as a comparator for future studies. Patients and MethodsWe performed a retrospective cohort review of patients with relapsed and refractory ALL previously treated at TACL institutions between the years of 1995 and 2004. Data regarding initial and relapsed disease characteristics, disease response, and survival were collected and compared with those of published reports. ResultsComplete remission (CR) rates (mean Ϯ SE) were 83% Ϯ 4% for early first marrow relapse, 93% Ϯ 3% for late first marrow relapse, 44% Ϯ 5% for second marrow relapse, and 27% Ϯ 6% for third marrow relapse. Five-year DFS rates in CR2 and CR3 were 27% Ϯ 4% and 15% Ϯ 7% respectively. ConclusionWe generally confirm a 40% CR rate for second and subsequent relapse, but our remission rate for early first relapse seems better than that reported in the literature (83% v approximately 70%). Our data may allow useful modeling of an expected remission rate for any population of patients who experience relapse.

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“…In the haematopoietic system, heparanase is expressed in platelets, neutrophils, macrophages and activated lymphocytes, where it mediates extravasation during inflammatory and immune responses. 2 In contrast to normal tissues, heparanase is widely expressed in primary human tumours where high levels of expression are correlated with increased local and distant metastasis, increased tumour…”

Section: Letters To the Editormentioning

confidence: 99%

“…2 In the study reported by Kolb and Steinherz, 2 28 children were treated with TVTG protocol, of which 13 (47%) achieved significant response with acceptable toxicities and 10 (36%) underwent haematopoietic stem cell transplantation. In view of these promising results in the children, we introduced TVTG regimen in adults who have been heavily pretreated for relapsed or refractory leukaemia and high-grade non-hodgkin's lymphoma.…”

mentioning

confidence: 99%

The feasibility of using topotecan, vinorelbine, thiotepa and gemcitabine (TVTG) in adult patients with relapsed/refractory acute lymphoblastic leukaemia/lymphoma

et al. 2008

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A new multidrug reinduction protocol with topotecan, vinorelbine, thiotepa, dexamethasone, and gemcitabine for relapsed or refractory acute leukemia

Cited by 39 publications

References 35 publications

Phase II study of topotecan in combination with dexamethasone, asparaginase, and vincristine in pediatric patients with acute lymphoblastic leukemia in first relapse

Phase II study of topotecan in combination with dexamethasone, asparaginase, and vincristine in pediatric patients with acute lymphoblastic leukemia in first relapse

Outcome of Patients Treated for Relapsed or Refractory Acute Lymphoblastic Leukemia: A Therapeutic Advances in Childhood Leukemia Consortium Study

The feasibility of using topotecan, vinorelbine, thiotepa and gemcitabine (TVTG) in adult patients with relapsed/refractory acute lymphoblastic leukaemia/lymphoma

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