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Human interferon beta, nimustine hydrochloride, and radiation therapy in the treatment of newly diagnosed malignant astrocytomas

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Summary

Previous investigators have reported encouraging results for malignant gliomas treated using a combination of human interferon beta (IFN-β) with nimustine hydrochloride (ACNU) and radiation therapy (termed IAR therapy). This study was undertaken to examine further the efficacy of the IAR regimen followed by maintenance therapy with IFN-β and ACNU in patients with newly diagnosed malignant astrocytomas. Fifty-eight patients were enrolled onto the trial. IFN-β (2 × 106 IU/m2/day × 5 days/week for 8 consecutive weeks) and ACNU (80 mg/m2 on days 1 and 36) were administered intravenously concomitant with radiation therapy followed by IFN-β (every 2 weeks) and ACNU (every 6 weeks). Of 33 patients assessable for a response, 11 responded (33%), with 4 complete responses. The estimated median overall survival (OS) was 16 months, with values of 58 and 13 months for anaplastic astrocytoma (AA) and glioblastoma (GB) patients, respectively. The overall progression free survival (PFS) was 11 months, with values of 31 and 7 months for AA and GB patients, respectively. The IAR therapy was safe and well tolerated. Based on a statistical analysis of the factors that affected the PFS and OS, histologic grade, postoperative Karnofsky performance scale (KPS), and extent of surgery were identified as independent predictors. The postoperative KPS stood out as the most powerful prognostic factor, which was also the best predictor for the response to IAR therapy. Our findings suggest a possible benefit for IAR therapy followed by maintenance therapy mainly in AA. In addition, they emphasize the importance of a preserved KPS after cytoreductive surgery, which could produce a potential benefit for adjuvant therapy and could ultimately lead to a prolonged survival.

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References

  • FW Kreth PC Warnke R Scheremet CB Ostertag (1993) ArticleTitleSurgical resection and radiation therapy versus biopsy and radiation therapy in the treatment of glioblastoma multiforme J Neurosurg 78 762–766

    Google Scholar 

  • M Lacroix D Abi-Said DR Fourney ZL Gokaslan W Shi F DeMonte FF Lang IE McCutcheon SJ Hassenbusch E Holland K Hess C Michael D Miller R Sawaya (2001) ArticleTitleA multivariate analysis of 416 patients with glioblastoma multiforme: prognosis, extent of resection, and survival J Neurosurg 95 190–198 Occurrence Handle1:STN:280:DC%2BD38%2FlsFGitA%3D%3D

    CAS  Google Scholar 

  • M Nagai T Arai (1984) ArticleTitleClinical effect of interferon in malignant brain tumors Neurosurg Rev 7 55–64

    Google Scholar 

  • JC Buckner PJ Schomberg WL McGinnis TL Cascino BW Scheithauer JR O’Fallon RF Morton SA Kuross JA Mailliard AK Hatfield JT Cole PD Steen AM Bernath (2001) ArticleTitleA phase III study of radiation therapy plus carmustine with or without recombinant interferon-α in the treatment of patients with newly diagnosed high-grade glioma Cancer 92 420–433

    Google Scholar 

  • WKA Yung M Prados LA Levin MR Fetel J Bennett MS Mahaley M Salcman E Etcubanas (1991) ArticleTitleIntravenous recombinant interferon β in patients with recurrent malignant gliomas: a phase I/II study J Clin Oncol 9 1945–1949 Occurrence Handle1:STN:280:By2D2cvntVM%3D Occurrence Handle1658242

    CAS  PubMed  Google Scholar 

  • HA Fine PY Wen M Robertson A O’Neill J Kowal JS Loeffler PML Black (1997) ArticleTitleA phase I trial of a new recombinant human β-interferon (BG9015) for the treatment of patients with recurrent gliomas Clin Cancer Res 3 381–387

    Google Scholar 

  • S Yamamoto K Tanaka M Kanamori M Nobuhara M Nanbara (1983) ArticleTitleIn vitro studies on potentiation of cytotoxic effects of anticancer drugs by interferon on a human neoplastic cell line (HeLa) Cancer 20 131–138

    Google Scholar 

  • M Nagai (1991) ArticleTitleAdvances of BRM therapy of malignant brain tumors Gan to Kagaku Ryoho 18 188–194

    Google Scholar 

  • T Wakabayashi N Hatano Y Kajita T Yoshida M Mizuno K Taniguchi T Ohno T Nagasaki J Yoshida (2000) ArticleTitleInitial and maintenance combination treatment with Interferon-beta, MCNU (Ranimustine), and radiotherapy for patients with previously untreated malignant glioma J Neuro-Oncol 49 57–62

    Google Scholar 

  • P Kleihues WK Cavenee (2000) Pathology and Genetics of Tumours of the Nervous System. International Agency for Research on Cancer Lyon

    Google Scholar 

  • Y Katayama T Tsubokawa S Maejima T Hirayama T Yamamoto (1998) ArticleTitleCortical direct response in humans: indication of the motor cortex during intracranial surgery under general anesthesia J Neurol Neurosurg Psychiatry 51 50–59

    Google Scholar 

  • C Fukaya Y Katayama A Yoshino K Kobayashi M Kasai T Yamamoto (2001) ArticleTitleIntraoperative wake-up procedure with propofol and laryngeal mask for optimal excision of brain tumour in eloquent areas J Clin Neurosci 8 253–255

    Google Scholar 

  • NCI: Common Toxicity Criteria. National Cancer Institute, Division of Cancer Treatment, Bethesda, MD, 1988

  • DF Nelson WJ Curran SuffixJr C Scott JS Nelson AS Weinstein K Ahmad LS Constine K Murray WD Powlis M Mohiuddin (1993) ArticleTitleHyperfractionated radiation therapy and bis-chlorethylnitrosourea in the treatment of malignant glioma: possible advantage observed at 72.0 Gy in 1.2 Gy B.I.D fractions: report of the Radiation Therapy Oncology Group Protocol 8302 Int J Radiat Oncol Biol Phys 25 193–207

    Google Scholar 

  • VA Levin MR Prados WM Wara RL Davis PH Gutin TL Phillips K Lamborn CB Wilson (1995) ArticleTitleRadiation therapy and bromodeoxyuridine chemotherapy followed by procarbazine, lomustine, and vincristine for the treatment of anaplastic gliomas Int J Radiat Oncol Biol Phys 32 75–83

    Google Scholar 

  • The Medical Research Council Brian Tumour Working Party: 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, 2001

    Google Scholar 

  • J Yoshida Y Kajita T Wakabayashi K Sugita (1994) ArticleTitleLong-term follow up results of 175 patients with malignant gliomas: importance of radical tumor resection and postoperative adjuvant therapy with interferon, ACNU and radiation Acta Neurochir (Wien) 127 55–59

    Google Scholar 

  • N Hatano T Wakabayashi Y Kajita M Mizuno T Ohno N Nakayashiki A Takemura J Yoshida (2000) ArticleTitleEfficacy of postoperative adjuvant therapy with human interferon beta, MCNU and radiation (IMR) for malignant glioma: comparison among three protocols Acta Neurochir (Wien) 142 633–639

    Google Scholar 

  • FK Albert M Forsting K Sartor HP Adams S Kunze (1994) ArticleTitleEarly postoperative magnetic resonance imaging after resection of malignant glioma: objective evaluation of residual tumor and its influence on regrowth and prognosis Neurosurgery 34 45–60 Occurrence Handle1:STN:280:ByuC28npslQ%3D Occurrence Handle8121569

    CAS  PubMed  Google Scholar 

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Correspondence to Takao Watanabe.

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Watanabe, T., Katayama, Y., Yoshino, A. et al. Human interferon beta, nimustine hydrochloride, and radiation therapy in the treatment of newly diagnosed malignant astrocytomas. J Neurooncol 72, 57–62 (2005). https://doi.org/10.1007/s11060-004-2160-x

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  • DOI: https://doi.org/10.1007/s11060-004-2160-x

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