Topotecan (Hycamptin) and Topotecan‐Containing Regimens in the Treatment of Hematologic Malignancies

Beran, Miloslav; Kantarjian, Hagop M.

doi:10.1111/j.1749-6632.2000.tb07043.x

Cited by 12 publications

(4 citation statements)

References 25 publications

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“…Other investigators have reported the efficacy of topotecan in the treatment of lymphoma and myelodysplastic syndromes (16). In these lymphoma studies, investigators used daily 30-minute infusion of topotecan alone or with etoposide or paclitaxel.…”

Section: Discussionmentioning

confidence: 99%

Activity of topotecan 21-day infusion in patients with previously treated large cell lymphoma: long-term follow-up of an Eastern Cooperative Oncology Group study (E5493)

Wiernik

Weller

et al. 2012

Leukemia & Lymphoma

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The purpose of this study was to determine the activity of topotecan given by 21-day continuous infusion in patients previously treated with one prior therapy for a diffuse large cell lymphoma or immunoblastic lymphoma. Patients with appropriate histology and measurable disease who had been treated with one prior chemotherapy regimen were eligible for study. Slides of tumor biopsies were submitted for central review of pathology. Patients were required to have ECOG performance status of 0, 1, or 2 and adequate bone marrow function. Patients were treated with continuous infusion topotecan, 0.4 mg/m2/day × 21 days. Therapy could be escalated to 0.5 and then 0.6 mg/m2/day in subsequent cycles if there was no dose limiting toxicity at the initial dose level. Patients were treated with 2 cycles after achieving complete response or until disease progression or unacceptable toxicity occurred. Thirty seven patients were enrolled, however, only 26 cases were eligible due to performance status of > 2 (2), more than one prior chemotherapy (1), and wrong histology on review (8). Due to the unexpectedly high ineligibility rate, two sets of analysis were done for all the 37 patients enrolled and for the 26 eligible patients, respectively. Of the 37 patients (15 males and 22 females), international prognostic index included 11% low risk, 30% low-intermediate risk; 46% high-intermediate risk, and 8% high risk. The median follow up was 77 months. A total of 136 cycles of therapy were given with a median of 3 cycles per patient. Grade 4 toxicities included: 14% grade 4 thrombocytopenia; 14% grade 4 granulocytopenia, 8% leukopenia, 3% each anemia, hemorrhage, infection, vomiting, thrombosis, liver toxicity, and neuromotor toxicity. The response analysis including all 37 patients showed 5 complete remissions (CR) and 4 partial remissions (PR) for a total response rate of 24% (90% two-stage confidence interval 13–39%). Median progression free survival (PFS) was 3.7 months, with one and two year PFS of 21% and 6% respectively (90% confidence interval 11–34% and 2–15%). Median overall survival (OS) was 10.5 months, with one and two year OS 41% and 27% respectively (90% confidence interval 27–53% and 16–39%). Analysis including only eligible patient showed similar response rates and survival outcomes. Single agent topotecan has moderate activity for previously treated high grade lymphoma equivalent to that of several newer agents, and should be considered for incorporation into multi-drug salvage chemotherapy programs.

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Section: Discussionmentioning

confidence: 99%

Activity of topotecan 21-day infusion in patients with previously treated large cell lymphoma: long-term follow-up of an Eastern Cooperative Oncology Group study (E5493)

Wiernik

Weller

et al. 2012

Leukemia & Lymphoma

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“…Phase II studies in adults based on prolonged exposure (primarily daily × 5 administered every 3 weeks) achieved encouraging results for the treatment of ovarian carcinoma [25,26] and small cell lung cancer [27,28] and in myelodysplastic syndrome and chronic myelomonocytic leukemia [29]. Phase II studies in children confirmed the achievement of improved outcomes when topotecan was administered for 5 consecutive days both in neuroblastoma and rhabdomyosarcoma [10,13,14].…”

Section: Introductionmentioning

confidence: 99%

Initial testing of topotecan by the pediatric preclinical testing program

Carol

Houghton

Morton

et al. 2010

Pediatric Blood & Cancer

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“…Novel agents are required to improve the prognosis of patients with myeloid leukemias 1. The topoisomerase I (topo I) inhibitor topotecan has demonstrated significant activity, both as a single agent and in combinations, in patients with acute myeloid leukemia (AML) or myelodysplastic syndromes (MDS) 1–10. In single‐agent studies, other topo I inhibitors, including 9‐aminocamptothecin and DX‐8951f, also have demonstrated antileukemia activity in both severe combined immunodeficient (SCID) mouse models of human leukemia and in Phase I studies 11–14.…”

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confidence: 99%

Phase I and pharmacokinetic study of a low‐clearance, unilamellar liposomal formulation of lurtotecan, a topoisomerase 1 inhibitor, in patients with advanced leukemia

Giles

Tallman

Garcia‐Manero

et al. 2004

Cancer

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BACKGROUND OSI‐211 is a low‐clearance, unilamellar liposomal formulation of a water‐soluble camptothecin analogue, lurtotecan. OSI‐211 has significant activity in severe combined immunodeficient mouse models of human leukemia. METHODS This study was conducted to define the dose‐limiting toxicities (DLT) and pharmacokinetics of OSI‐211 in patients with refractory myeloid leukemias. Patients with refractory acute myeloid leukemia (AML), myelodysplastic syndrome (MDS), or chronic myelogenous leukemia in blastic phase (CML‐BP) were eligible. OSI‐211 was given as an intravenous infusion over 30 minutes daily for 3 days. The starting dose was 1.5 mg/m2 per day (4.5 mg/m2 per course). The dose was escalated by 50% until Grade 2 toxicity was observed and then by 30–35% until the DLT was defined. Serial plasma and urine samples were collected, and drug levels were determined by high‐performance liquid chromatography with fluorescence detection. RESULTS Twenty patients (18 patients [90%] with AML, and 1 patient each [5%] with MDS and CML‐BP) were treated. Mucositis and diarrhea were considered to be the DLTs. The maximum tolerated dose was 3.7 mg/m2 per day. Fourteen of 18 evaluable patients (78%) with AML or MDS achieved transient bone marrow aplasia. The mean systemic clearance of lurtotecan in plasma was 0.946 ± 1.53 L/hour/m2. Urinary recovery of lurtotecan was 6.66% ± 5.26% (range, 1.05–18.4%). CONCLUSIONS Liposomal encapsulation of lurtotecan altered its metabolism significantly. There was no evident correlation between exposure, as measured by plasma pharmacokinetics of lurtotecan, and clinical response or toxicities. OSI‐211 merits further study in hematologic malignancies. Cancer 2004;100:1449–58. © 2004 American Cancer Society.

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Topotecan (Hycamptin) and Topotecan‐Containing Regimens in the Treatment of Hematologic Malignancies

Cited by 12 publications

References 25 publications

Activity of topotecan 21-day infusion in patients with previously treated large cell lymphoma: long-term follow-up of an Eastern Cooperative Oncology Group study (E5493)

Activity of topotecan 21-day infusion in patients with previously treated large cell lymphoma: long-term follow-up of an Eastern Cooperative Oncology Group study (E5493)

Initial testing of topotecan by the pediatric preclinical testing program

Phase I and pharmacokinetic study of a low‐clearance, unilamellar liposomal formulation of lurtotecan, a topoisomerase 1 inhibitor, in patients with advanced leukemia

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