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CPT-11 for recurrent temozolomide-refractory 1p19q co-deleted anaplastic oligodendroglioma

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Abstract

Objective A Phase II study of CPT-11 in adults with recurrent, temozolomide (TMZ)-refractory, 1p19q co-deleted, anaplastic oligodendroglioma (AO) with a primary objective of determining 6-month progression free survival (PFS). Background There is no standard therapy for alkylator-resistant AO. Methods Twenty-two patients (11 men; 11 women) ages 26–65 (median 40), with radiographically recurrent AO were enrolled. All patients had previously been treated with surgery, involved-field radiotherapy, and adjuvant chemotherapy (TMZ in 15; BCNU in 6). Fifteen patients were treated at first recurrence with an alternative chemotherapy. 13 patients underwent repeat surgery. All patients were treated at either first or second recurrence with CPT-11 administered intravenously once every 3 weeks. Neurological and neuroradiographic evaluations were performed every 8–9 weeks. Results All patients were evaluable for toxicity and response. A total of 141 cycles of CPT-11 (median 3 cycles; range 3–18) were administered. CPT-11 related toxicity included diarrhea (14 patients; 4 grade 3), neutropenia (8; 4 grade 3), fatigue (12; 3 grade 3), and delayed nausea/vomiting (12; 3 grade 3). 5 patients (23%) demonstrated a partial radiographic response, 8 (36%) demonstrated stable disease and 9 (41%) had progressive disease following three cycles of CPT-11. Time to tumor progression ranged from 2 to 13.5 months (median: 4.5 months). Survival ranged from 3 to 21 months (median: 5.5 months). Six-month and 12-month PFS were 33% and 4.5% respectively. Conclusions CPT-11 demonstrated modest efficacy (similar to other salvage glioma regimens) with acceptable toxicity in this cohort of adults with recurrent, 1p19q co-deleted AO all of whom had failed prior TMZ chemotherapy.

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Authors and Affiliations

  1. Department of Neurology and Neurological Surgery, University of Washington, Seattle, WA, USA

    Marc C. Chamberlain

  2. Fred Hutchinson Cancer Center, Seattle Cancer Care Alliance, 825 Eastlake Ave E, MS: G4-940, POB 19023, Seattle, WA, 98109-1023, USA

    Marc C. Chamberlain

  3. Departments of Oncology and Neurosurgery, Huntsman Cancer Institute, Salt Lake City, UT, USA

    Michael J. Glantz

  4. University of Utah School of Medicine, Salt Lake City, UT, USA

    Michael J. Glantz

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  1. Marc C. Chamberlain
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Correspondence to Marc C. Chamberlain.

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Michael J. Glantz, Huntsman Cancer Institute/University of Utah School of Medicine conducted the statistical analysis for this manuscript.

Both authors listed above collected and analyzed data.

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Chamberlain, M.C., Glantz, M.J. CPT-11 for recurrent temozolomide-refractory 1p19q co-deleted anaplastic oligodendroglioma. J Neurooncol 89, 231–238 (2008). https://doi.org/10.1007/s11060-008-9613-6

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