Phase II study of ifosfamide, carboplatin, and etoposide in patients with a first recurrence of glioblastoma multiforme

Clinical article

Tomokazu Aoki Departments of Neurosurgery,

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Tomohiko Mizutani Department of Neurosurgery, Hyogo Prefectural Amagasaki Hospital;

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Kuniharu Nojima Department of Neurosurgery, Ako City Hospital, Hyogo;

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Takehisa Takagi Radiation Oncology,

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Ryosuke Okumura Radiology,

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Yoshiaki Yuba Pathology, Kitano Hospital Medical Research Institute;

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Tetsuya Ueba Department of Neurosurgery, Kishiwada City Hospital;

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Jun A. Takahashi Departments of Neurosurgery,

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Shin-Ichi Miyatake Department of Neurosurgery, Osaka Medical College, Osaka;

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Kazuhiko Nozaki Department of Neurosurgery, Shiga University of Medical Science, Shiga;

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Waro Taki Department of Neurosurgery, Faculty of Medicine, Mie University, Mie;

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Masao Matsutani Department of Neurosurgery, Saitama Medical University International Medical Center, Saitama, Japan

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Object

The prognosis of recurrent glioblastoma multiforme (GBM) remains unsatisfactory. The authors conducted a Phase II study of ifosfamide, carboplatin, and etoposide (ICE) for a first recurrence of GBM to determine whether it prolonged a patient's good-quality life.

Methods

This trial was an open-label, single-center Phase II study. Forty-two patients with a first GBM relapse after surgery followed by standard radiotherapy (60 Gy) and first-line temozolomide- or nimustine-based chemotherapy were eligible to participate. The primary end point was progression-free survival at 6 months after the ICE treatment (PFS-6), and secondary end points were response rate, toxicity, and overall survival. Chemotherapy consisted of ifosfamide (1000 mg/m2 on Days 1, 2, and 3), carboplatin (110 mg/m2 on Day 1), etoposide (100 mg/m2 on Days 1, 2, and 3), every 6 weeks.

Results

Progression-free survival at 6 months after ICE treatment was 35% (95% CI 22–50%). The median duration of PFS was 17 weeks (95% CI 10–24 weeks). The response rate was 25% (95% CI 9–34%). Adverse events were generally mild and consisted mainly of alopecia.

Conclusions

This regimen was well tolerated and has some activity and could be one of the options for patients with recurrent GBM.

Abbreviations used in this paper:

CR = complete response; GBM = glioblastoma multiforme; ICE = ifosfamide-carboplatin-etoposide; KPS = Karnofsky Performance Scale; MGMT = O6-methylguanine-DNA methyltransferase; NCI = National Cancer Institute; NR = no response; PFS = progression-free survival; PR = partial response.
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  • 1

    Aoki T, , Hashimoto N, & Matsutani M: Management of glioblastoma. Expert Opin Pharmacother 8:31333146, 2007

  • 2

    Aoki T, , Takahashi JA, , Ueba T, , Oya N, , Hiraoka M, & Matsui K, et al.: Phase II study of nimustine, carboplatin, vincristine, and interferon-b with radiotherapy for glioblastoma multiforme: experience of the Kyoto Neuro-Oncology Group. J Neurosurg 105:385391, 2006

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 3

    Brada M, , Hoang-Xuan K, , Ramoling R, , Dietrich PY, , Dirix LY, & Macdonald D, et al.: Multicenter phase II trial of temozolomide in patients with glioblastoma multiforme at first relapse. Ann Oncol 12:259266, 2001

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 4

    Brandes AA, , Basso U, , Reni M, , Vastola F, , Tosoni A, & Cavallo G, et al.: First line chemotherapy with cisplatin plus fractionated temozolomide (bid) in recurrent glioblastoma multiforme. A phase II study of the Gruppo Italiano Cooperativo Neuro-Oncologia (GICNO). J Clin Oncol 22:15981604, 2004

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 5

    Brandes AA, , Tosoni A, , Basso U, , Reni M, , Valduga F, & Monfardini S, et al.: Second-line chemotherapy with irinotecan plus carmustine in glioblastoma recurrent or progressive after fine-line temozolomide chemotherapy: a phase II study of the Gruppo Italiano Cooperatvo di Neuro-Oncologia (GICNO). J Clin Oncol 22:47794786, 2004

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 6

    Brandes AA, , Tosoni A, , Cavallo G, , Bertorelle R, , Gioia V, & Franceschi E, et al.: Temozolomide 3 weeks on and 1 week off as first-line therapy for recurrent glioblastoma: phase II study from gruppo italiano cooperativo di neuro-oncologia (GICNO). Br J Cancer 95:11551160, 2006

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 7

    Brandes AA, , Tosoni AT, , Spagnolli F, , Frezza G, , Leonardi M, & Calbucci F, et al.: Disease progression or pseudoprogression after concomitant radiochemotheray treatment: pitfalls in neurooncology. Neuro Oncol 10:361367, 2008

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 8

    Brandsma D, , Stalpers L, , Taal W, , Sminia P, & van den Bent MJ: Clinical features, mechanisms, and management of pseudoprogression in malignant gliomas. Lancet Oncol 9:453461, 2008

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 9

    Butowski NA, , Sneed PK, & Chang SM: Diagnosis and treatment of recurrent high-grade astrocytoma. J Clin Oncol 24:12731280, 2006

  • 10

    Chamberlain MC: Bevacizumab plus irinotecan in recurrent glioblastoma. J Clin Oncol 26:10121013, 2008

  • 11

    Cloughesy TF, , Prados MD, , Wen PY, , Mikkelsen T, , Abrey LE, & Schiff D, et al.: A phase II, randomized, non-comparative clinical trial of the effect of bevacizumab (BV) alone or in combination with irinotecan (CPT) on 6-month progression free survival (PFS6) in recurrent, treatment-refractory glioblastoma (GBM). J Clin Oncol 26:Suppl 2010b, 2008. (Abstract)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 12

    Fine HA, , Wen PY, , Maher EA, , Viscosi E, , Batchelor T, & Lakhani N, et al.: Phase II study trial of thalidomide and carmustine for patients with recurrent high-grade gliomas. J Clin Oncol 21:22992304, 2003

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 13

    Groves MD, , Puduvalli VK, , Hess KR, , Jaeckle KA, , Peterson P, & Yung WK, et al.: Phase II trial of temozolomide plus matrix metalloproteinase inhibitor, marimastat, in recurrent and progressive glioblastoma multiforme. J Clin Oncol 20:13831388, 2002

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 14

    Hegi ME, , Diserens AC, , Gorlia T, , Hamou MF, , de Tribolet N, & Weller M, et al.: MGMT gene silencing and benefit from temozolomide in glioblastoma. N Engl J Med 352:9971003, 2005

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 15

    Jaeckle KA, , Hess KR, , Yung A, , Greenberg H, , Fine H, & Schiff D, et al.: 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 21:23052311, 2003

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 16

    Jeremic B, , Grujicic D, , Jevremovic S, , Stanisavljevic B, , Milojevic L, & Djuric L, et al.: Carboplatin and etoposide chemotherapy regimen for recurrent malignant glioma: a phase II study. J Clin Oncol 10:10741077, 1992

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 17

    Kappelle AC, , Postma TJ, , Taphoorn MJ, , Groeneveld GJ, , van den Bent MJ, & van Groeningen CJ, et al.: PCV chemotherapy for recurrent glioblastoma multiforme. Neurology 56:118120, 2001

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 18

    Macdonald DR, , Cascino TL, , Schold SC Jr, & Cairncross JG: Response criteria for phase II studies of supratentorial malignant glioma. J Clin Oncol 8:12771280, 1990

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 19

    Marina NM, , Rodman J, , Shema SJ, , Bowman LC, , Douglass E, & Furman W, et al.: Phase I study of escalating targeted doses of carboplatin combined with ifosfamide and etoposide in children with relapsed solid tumors. J Clin Oncol 11:554560, 1993

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 20

    Sanson M, , Ameri A, , Monjour A, , Sahmoud T, , Ronchin P, & Poisson M, et al.: Treatment of recurrent malignant supratentorial gliomas with ifosfamide, carboplatin and etoposide: a phase II study. Eur J Cancer 32A:22292235, 1996

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 21

    Schrag D, & Hanger M: Medical oncologists' view on communicationg with patients about chemotherapy costs: a pilot survey. J Clin Oncol 25:233237, 2007

  • 22

    Stupp R, , Mason WP, , van den Bent MJ, , Weller M, , Fisher B, & Taphoorn MJ, et al.: Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N Engl J Med 352:987996, 2005

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 23

    Takahashi Y, & Nishioka K: Survival without tumor shrinkage: re-evaluation of survival gain by cytostatic effect of chemotherapy. J Natl Cancer Inst 87:12621263, 1995

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 24

    Tolcher AW, , Gerson SL, , Denis L, , Geyer C, , Hammond LA, & Patnaik A, et al.: Marked inactivation of O6-alkylguanine-DNA alkyltransferase activity with protracted temozolomide schedules. Br J Cancer 88:10041011, 2003

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 25

    Vecht CJ, , Wagner GL, & Wilms EB: Interractions between antiepileptic and chemotherapeutic drugs. Lancet Neurol 2:404409, 2003

  • 26

    Vredenburgh JJ, , Desjardins A, , Herndon JE II, , Dowell JM, , Reardon DA, & Quinn JA, et al.: Phase II trial of bevacizumab and irinotecan in recurrent malignant glioma. Clin Cancer Res 13:12531259, 2007

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 27

    Vredenburgh JJ, , Desjardins A, , Herndon JE II, , Marcello J, , Reardon DA, & Quinn JA, et al.: Bevacizumab plus irinotecan in recurrent glioblastoma multiforme. J Clin Oncol 25:47224729, 2007

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 28

    Wasserfallen JB, , Ostermann S, , Leyvraz S, & Stupp R: Cost of temozolomide therapy and global care for recurrent malignant gliomas followed until death. Neuro Oncol 7:189195, 2005

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 29

    Westphal M, , Hilt DC, , Bortey E, , Delavault P, , Olivares R, & Warnke PC, et al.: A phase 3 trial of local chemotherapy with biodegradable carmustine (BCNU) wafers (Gliadel wafers) in patients with primary malignant glioma. Neuro Oncol 5:7988, 2003

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 30

    Wick A, , Felsberg J, , Steinbach JP, , Herrlinger U, , Platten M, & Blaschke B, et al.: Efficacy and tolerability of temozolomide in an alternating weekly regimen in patients with recurrent glioma. J Clin Oncol 25:33573361, 2007

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 31

    Wong ET, , Hess KR, , Gleason MJ, , Jaeckle KA, , Kyritsis AP, & Prados MD, et al.: Outcomes and prognostic factors in recurrent glioma patients enrolled onto phase II clinical trials. J Clin Oncol 17:25722578, 1999

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 32

    Yung WK, , Albright RE, , Olson J, , Fredericks R, , Fink K, & Prados MD, et al.: A phase II study of temozolomide vs. procarbazine in patients with glioblastoma multiforme at first relapse. Br J Cancer 83:588593, 2000

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 33

    Yung WK, , Mechtler L, & Gleason MJ: Intravenous carboplatin for recurrent malignant glioma: a phase II study. J Clin Oncol 9:860864, 1991

  • 34

    Zalupski M, & Baker LH: Ifosfamide. J Natl Cancer Inst 80:556566, 1988

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