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A phase II trial of oral gimatecan for recurrent glioblastoma

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Abstract

Gimatecan is a lipophilic oral camptothecin analogue with preclinical activity in glioma models. We conducted a multicenter phase II trial to evaluate the efficacy of gimatecan in adults with recurrent glioblastoma. Eligibility criteria included ≤1 prior treatment for recurrent disease, age ≥18, Eastern Cooperative Oncology Group performance status 0–1, and normal organ function. Patients taking enzyme-inducing anti-seizure medications were excluded. Gimatecan 1.22 mg/m2 was given orally once daily for 5 consecutive days during each 28-day cycle. The primary endpoint was progression-free survival at 6 months. A Simon 2-stage optimal design was used in which 19 patients were evaluated in the 1st stage, with an additional 36 patients accrued if >4 patients in stage 1 achieved PFS at 6 months. 29 patients were enrolled in the study, with median age of 58 years (range, 25–77 years); 58.6 % female. All patients received prior surgery, radiation therapy, and at least one chemotherapy regimen. The daily dose was reduced to 1.0 mg/m2 after four of the first 10 patients experienced grade 4 hematologic toxicity. Treatment-related grade 3/4 toxicities included thrombocytopenia (17.2 %), leukopenia (17.2 %) and neutropenia (10.3 %). None of the 19 patients treated at 1.0 mg/m2/day experienced grade 4 hematologic toxicity. One patient had a partial radiographic response by modified Macdonald criteria. Only 3 patients (12 %) were progression-free at 6 months. Median time to progression was 12.0 weeks (7.0, 17.0).Treatment with gimatecan 1.0 mg/m2/day for 5 days, repeated every 28-days showed minimal efficacy.

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Acknowledgments

Grant support from Sigma-Tau Research.

Conflict of interest

N. Salem is employed by Sigma-Tau.

Ethical standards

This study complies with the current laws of the United States of America.

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Authors and Affiliations

  1. Johnnie L. Cochran Jr. Brain Tumor Center, 8631 West Third St, Suite 410E, Los Angeles, CA, 90048, USA

    Jethro Hu

  2. Center For Neuro-Oncology, Dana-Farber Cancer Institute, 450 Brookline Avenue SW 430D, Boston, MA, 02215, USA

    Patrick Y. Wen

  3. Department of Neurology, University of Zurich, Frauenklinikstrasse 26, Zurich, Switzerland

    Lauren E. Abrey

  4. Norris Cotton Cancer Center, Dartmouth Hitchcock Medical Center, One Medical Center Drive, Lebanon, NH, 03756, USA

    Camilo E. Fadul

  5. UPMC Cancer Pavilion, 5150 Centre Avenue, Pittsburgh, PA, 15232, USA

    Jan Drappatz

  6. Sigma-Tau Pharmaceuticals Inc., 9841 Washingtonian Blvd., Suite 500, Gaithersburg, MD, 20878, USA

    Nadia Salem

  7. Clinical Pharmacology Laboratory, Massachusetts General Hospital, 55 Fruit Street, Boston, MA, 02114, USA

    Jeffrey G. Supko

  8. Stephen E. & Catherine Pappas Center for Neuro-Oncology, Massachusetts General Hospital Cancer Center, Harvard Medical School, 55 Fruit Street, YAW 9E, Boston, MA, 02114, USA

    Fred Hochberg

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  1. Jethro Hu
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Correspondence to Jethro Hu.

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Hu, J., Wen, P.Y., Abrey, L.E. et al. A phase II trial of oral gimatecan for recurrent glioblastoma. J Neurooncol 111, 347–353 (2013). https://doi.org/10.1007/s11060-012-1023-0

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  • DOI: https://doi.org/10.1007/s11060-012-1023-0

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