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Topotecan, cyclophosphamide, and etoposide (TCE) in the treatment of high-risk neuroblastoma. Results of a phase-II trial

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Abstract

Purpose

Relapsed high-risk neuroblastoma patients still have a poor prognosis. This phase-II trial assessed a new topotecan containing chemotherapy approach in patients with active disease.

Methods

Chemotherapy consisted of topotecan (1.0 mg/m2/day 168-h continuous infusion), cyclophosphamide (100 mg/m2/day 1-h-infusion days 1–7 starting 6 h prior to topotecan), and etoposide (100 mg/m2/day 1-h-infusion days 8–10). Patients with relapsed neuroblastoma were scheduled for six cycles, untreated patients for two cycles followed by standard high-risk treatment.

Results

Main toxicity observed during 153 cycles were grade 3–4 leukopenia (97% of cycles), thrombocytopenia (92%), neutropenic fever (52%), and mucositis (10%). No treatment related fatal toxicity occurred. Complete or partial response was achieved in 19 of 31 (61%) evaluable relapsed patients and 8 of 11 (72%) untreated patients.

Conclusions

The combination of topotecan, cyclophosphamide, and etoposide is tolerable and effective in relapsed and untreated neuroblastoma. Myelotoxicity is the main side effect but seems justified in view of the encouraging response rates. A randomized phase-III trial in primary disease has been commenced.

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Acknowledgments

We thank the following investigators for the participation in the study: R Mertens (Aachen), A Gnekow (Augsburg), G Henze (Berlin), U Bode (Bonn), W Eberl (Braunschweig), I Krause (Chemnitz), R Frank (Coburg), T Wiesel (Datteln), M Suttorp (Dresden), T Klingebiel (Frankfurt), A Reiter (Giessen), A Kulozik (Heidelberg), N Graf (Homburg/Saar), M Wright (Kassel), S Völpel (Krefeld), B Selle (Ludwigshafen), A Jobke (Nuremberg), O Peters (Regensburg), H-G Scheel-Walther (Tübingen), P-G Schlegel (Würzburg), and F Niggli (Zurich).

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Authors and Affiliations

  1. Children’s Hospital, Department of Pediatric Oncology and Hematology, University of Cologne, Kerpener Strasse 62, 50924, Cologne, Germany

    Thorsten Simon, Frank Berthold & Barbara Hero

  2. Department of Pediatrics, Gemeinschaftskrankenhaus, Herdecke, Germany

    Alfred Längler

  3. Coordination Center for Clinical Trials, University of Cologne, Cologne, Germany

    Urs Harnischmacher

  4. Department of Pediatric Hematology and Oncology, University Children’s Hospital Muenster, Muenster, Germany

    Michael C. Frühwald

  5. Gilead Children’s Hospital, Bielefeld, Germany

    Norbert Jorch

  6. Children’s Hospital, University of Kiel, Kiel, Germany

    Alexander Claviez

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  1. Thorsten Simon
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  8. Barbara Hero
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Correspondence to Thorsten Simon.

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Simon, T., Längler, A., Harnischmacher, U. et al. Topotecan, cyclophosphamide, and etoposide (TCE) in the treatment of high-risk neuroblastoma. Results of a phase-II trial. J Cancer Res Clin Oncol 133, 653–661 (2007). https://doi.org/10.1007/s00432-007-0216-y

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  • DOI: https://doi.org/10.1007/s00432-007-0216-y

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