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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References
The Medical Research Council brain tumor working party (2000) Randomized trial of procarbazine, lomustine, and vincristine in the adjuvant treatment of high-grade astrocytoma: A Medical Research Council Trial. J Clin Oncol 19:509–518
Prados MD, Scott C, Curran WJ et al (1999) Procarbazine, lomustine, and vincristine (PCV) chemotherapy for anaplastic astrocytoma: a retrospective review of Radiation Therapy Oncology Group protocols comparing survival with carmustine or PCV adjuvant chemotherapy. J Clin Oncol 17:3389–3395
Westphal M, Hilt DC, Bortey E et al (2003) A phase 3 trial of local chemotherapy with biodegradable Carmustine (BCNU) wafers (Gliadel wafers) in patients with primary malignant glioma. Neuro Oncol 5(2):79–88
Grossman SA, O’Neill A, Grunnet M, Mehta M et al (2003) Phase III Study comparing three cycles of infusional carmustine and cisplatin followed by radiation therapy with radiation therapy and concurrent carmustine in patients with newly diagnosed supratentorial glioblastoma multiforme: Eastern Cooperative Oncology Group Trial 2394. J Clin Oncol 21:1485–1491
Prados MD, Levin V (2000) Biology and treatment of malignant glioma. Semin Oncol 27(Suppl 3):1–10
Gutin PH, Prados MD, Phillips TL et al (1991) External irradiation followed by an interstitial high activity iodine-125 implant “boost” in the initial treatment of malignant gliomas: NCOG Study 6G82-2. Int J Radiat Oncol Biol Phys 21:601
Loeffler JS, Alexander E, Shea WM et al (1992) Radiosurgery as part of the initial management of patients with malignant gliomas. J Clin Oncol 10(9):1379–1385
Prados MD, Gutin PH, Phillips TL et al (1992) Interstitial brachytherapy for newly diagnosed patients with malignant gliomas: the UCSF experience. Int J Radiat Oncol Biol Phys 24:593
Levin VA, Silver P, Hannigan J et al (1990) Superiority of post-radiotherapy adjuvant chemotherapy with CCNU, procarbazine, and vincristine (PCV) over BCNU for anaplastic gliomas: NCOG 6G61 final report. Int J Radiat Oncol Biol Phys 18:321–324
Glioma Meta-analysis Trialists Group (2002) Chemotherapy in adult high-grade glioma: a systemic review and meta-analysis of individual patient data from 12 randomized trials. Lancet 359:1011–1018
Fine HA, Dear KB, Loeffler JS et al (1993) Meta-analysis of radiation therapy and without chemotherapy for malignant gliomas in adults. Cancer 71:2585–2597
Prados MD, Gutin PH, Phillips TL et al (1992) Highly Anaplastic Astrocytoma: a review of 357 patients treated between 1977 and 1989. Int J Radiat Oncol Biol Phys 23:3–8
Wong ET, Hess KR, Gleason MJ et al (1999) Outcomes and prognostic factors in recurrent glioma patients enrolled onto phase II clinical trials. J Clin Oncol 17:2572–2578
Yung WKA, Mechtler L, Gleason MJ (1991) Intravenous carboplatin for recurrent malignant gliomas: a phase II study. J Clin Oncol 9:860
Yung WK, Prados MD, Yaya-Tur R, Rosenfeld SS, Brada M et al (1999) Multicenter Phase II trial of temozolomide in patients with anaplastic astrocytoma or anaplastic oligoastrocytoma at first relapse. J Clin Oncol 17:2762–2771
Longee DC, Friedman HS, Albright RE, Burger PC et al (1990) Treatment of patients with recurrent gliomas with cyclophosphamide and vincristine. J Neurosurg 72:583–588
Chamberlain MC, Tsao-Wei D (2004) Recurrent glioblastoma multiforme: salvage therapy with cyclophosphamide. Cancer 100:1213–1220
Brem H, Piantadosi S, Burger PC, Walker M, Selker R et al (1995) Placebo-controlled trial of safety and efficacy of intraoperative controlled delivery by biodegradable polymers of chemotherapy for recurrent gliomas. Lancet 345:1008–1012
Jaeckle KA, Hess KR, Yung A et al (2003) Phase II evaluation of temozolomide and 13-cis-retinoic acid for the treatment of recurrent and progressive malignant glioma: a North American Brain Tumor Consortium study. J Clin Oncol 21:2305–2311
Soffieti R, Nobile M, Rida F et al (2004) Second-line treatment with carboplatin for recurrent or progressive oligodendroglial tumors after PCV chemotherapy: a phase II study. Cancer 15:807–813
Brandes AA, Basso U, Vastola F et al (2003) Carboplatin and teniposide as third-line chemotherapy in patients with recurrent oligodendroglioma or oligoastrocytoma: a phase II study. Ann Oncol 14:1727–1731
Triebels VH, Taphoorn MJ, Brandes AA et al (2004) Salvage PCV chemotherapy for temozolomide resistant oligodendrogliomas. Neurology 63:904–906
Batchelor TT, Gilbert MR, Supko JG et al (2004) Phase 2 study of weekly irinotecan in adults with recurrent malignant glioma: Final report of NABTT 97–11. Neuro Oncol 6:21–27
Buckner JC, Reid JM, Wright K et al (2003) Irinotecan in the treatment of glioma patients: current and future studies of the North Cancer Central treatment Group. Cancer 97:2352–2358
Chamberlain MC (2002) Salvage chemotherapy with CPT-11 for recurrent glioblastoma. J Neurooncol 56:183–188
Cloughesy TF, Filka E, Kuhn J et al (2003) Two studies evaluating irinotecan treatment for recurrent malignant glioma using an every 3-week regimen. Cancer 97:2381–2386
Friedman HS, Petros WP, Friedman AH et al (1999) Irinotecan therapy in adults with progressive malignant glioma. J Clin Oncol 17:1516–1525
Prados MD, Yung WKA, Jaeckle KA et al (2004) Phase 1 trial of irinotecan (CPT-11) in patients with recurrent malignant glioma: a North American Brain Tumor Consortium study. Neuro Oncol 6:44–54
Prados MD, Lamborn K, Yung WKA et al (2006) A Phase 2 trial of irinotecan (CPT-11) in patients with recurrent malignant glioma: a North American Brain Tumor Consortium study. Neuro Oncol 8(2):189–193
Gilbert MR, Supko JG, Batchelor T et al (2003) A Phase I clinical and pharmacokinetic study of irinotecan in adults with recurrent malignant glioma. Clin Cancer Res 9:2940–2949
Macdonald DR, Cascino TL, Schold SC et al (1990) Response criteria for phase II studies of supratentorial malignant glioma. J Clin Oncol 8:1277–1280
Miller RG Jr (1981) Survival Analysis. Wiley, New York, pp 114–118
Pike MC (1972) Contribution to the discussion on the paper by R. Peto and J. Peto, ‘Asymptotically efficient rank invariant procedures’. J R Stat Soc Ser A 135:201–203
Berry G, Kitchin RM, Mock PA (1991) A comparison of two simple hazard ratio estimators based on the logrank test. Stat Med 10:749–755
Lawless JF (1982) Statistical models and methods for lifetime data. Wiley, New York, pp 345–354
Kaplan EL, Meier P (1958) Nonparametric estimation form incomplete observations. J Am Stat Assoc 53:457–481
Mantel N (1963) Chi-square tests with one degree of freedom: extensions of the Mantel-Haenszel procedure. J Am Stat Assoc 58:690–700
Mantel N, Haenszel W (1959) Statistical aspects of the analysis of data from retrospective studies of disease. J Natl Cancer Inst 22:719–748
van den Bent M, Brandes M, Frenay P et al (2005) Multicenter phase II study of imatinib mesylate in patients with recurrent anaplastic oligodendroglioma, anaplastic astrocytoma and low grade astrocytoma: an EORTC new drug development group and brain tumor group study. J Clin Oncol 23:118S (suppl: abstr 1528)
Cairncross G, Berkey B, Shaw E et al (2006) Phase III trial of chemotherapy plus radiotherapy compared with radiotherapy alone for pure and mixed anaplastic oligodendroglioma: Intergroup Radiation Oncology Group trial 9402. J Clin Oncol 24(18):2707–2714
Stupp R, Mason WP, Van Den Bent MJ et al (2004) Concomitant and adjuvant temozolomide and radiotherapy for newly diagnosed glioblastoma multiforme. Conclusive results of a randomized phase III trial by the EORTC Brain & RT Groups and NCIC Clinical Trial Groups. J Clin Oncol 22:1s
Triebels VH, Taphoorn MJ, Brandes AA et al (2004) PCV chemotherapy for temozolomide resistant oligodendrogliomas. Neurology 63:904–906
Jaeckle KA, Ballman RD, Jenkins RB, Buckner JC (2006) Current strategies in treatment of oligodendroglioma: evolution of molecular signatures of response. J Clin Oncol 24(8):1246–1252
Vrendenburgh JJ, Desjardins A, Herndon JE 2nd et al (2007) Phase II trial of bevacizumab and irinotecan in recurrent malignant glioma. Clin Cancer Res 13(4):1253–1259
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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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DOI: https://doi.org/10.1007/s11060-008-9613-6