Clinical Study

Journal of Neuro-Oncology

, Volume 111, Issue 3, pp 347-353

First online:

A phase II trial of oral gimatecan for recurrent glioblastoma

  • Jethro HuAffiliated withJohnnie L. Cochran Jr. Brain Tumor Center Email author 
  • , Patrick Y. WenAffiliated withCenter For Neuro-Oncology, Dana-Farber Cancer Institute
  • , Lauren E. AbreyAffiliated withDepartment of Neurology, University of Zurich
  • , Camilo E. FadulAffiliated withNorris Cotton Cancer Center, Dartmouth Hitchcock Medical Center
  • , Jan DrappatzAffiliated withUPMC Cancer Pavilion
  • , Nadia SalemAffiliated withSigma-Tau Pharmaceuticals Inc.
  • , Jeffrey G. SupkoAffiliated withClinical Pharmacology Laboratory, Massachusetts General Hospital
  • , Fred HochbergAffiliated withStephen E. & Catherine Pappas Center for Neuro-Oncology, Massachusetts General Hospital Cancer Center, Harvard Medical School

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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.


Gimatecan Glioblastoma Clinical trial Camptothecin Brain tumor Glioma