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High-grade astrocytoma treated concomitantly with estramustine and radiotherapy

  • Clinical–patient studies
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Summary

Experimental and early clinical investigations have demonstrated encouraging results for estramustine in the treatment of malignant glioma. The present study is an open randomized clinical trial comparing estramustine phosphate (Estracyt®) in addition to radiotherapy with radiotherapy alone as first line treatment of astrocytoma grade III and IV. The 140 patients included were in a good clinical condition with a median age of 55 years (range 22–87). Estramustine was given orally, 280 mg twice daily, as soon as the diagnosis was established, during and after the radiotherapy for a period of in total 3 months. Radiotherapy was delivered on weekdays 2 Gy daily up to 56 Gy. Eighteen patients were excluded due to misclassification, leaving 122 patients eligible for evaluation. Overall the treatment was well tolerated. Mild or moderate nausea was the most common side effect of estramustine. The minimum follow-up time was 5.2 years for the surviving patients. For astrocytoma grade III the median survival time was 10.6 (1.3–92.7) months for the radiotherapy only group and 17.3 (0.4–96.9+) months for the estramustine  + radiotherapy group. In grade IV the corresponding median survival time was 12.3 (2.1–89.2) and 10.3 (0.3–91.7+) months, respectively. Median time to progress for radiotherapy only and radiotherapy and estramustin group in grade III tumours was 6.5 and 10.1 months, respectively. In grade IV tumours the corresponding figures were 5.1 and 3.3 months, respectively. Although there was a tendency for improved survival in grade III, no statistical significant differences were found between the treatment groups. No differences between the two treatment groups were evident with respect to quality of life according to the EORTC QLQ-protocol. In conclusion, this first randomized study did not demonstrate any significant improvement of using estramustine in addition to conventional radiotherapy, however, a trend for a positive response for the estramustine group was found in patients with grade III glioma.

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References

  1. Stupp R, Mason WP, van den Bent MJ, et al. Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma N Engl J Med 352: 987–996, 2005

    Article  PubMed  CAS  Google Scholar 

  2. Bergenheim AT, Bjork P, Bergh J, von Schoultz E, Svedberg H, Henriksson R Estramustine-binding protein and specific binding of the anti-mitotic compound estramustine in astrocytoma Cancer Res 54: 4974–4979, 1994

    PubMed  CAS  Google Scholar 

  3. von Schoultz E, Gunnarsson PO, Henriksson R Uptake, metabolism and antiproliferative effect of estramustine phosphate in human glioma cell lines Anticancer Res 9: 1713–1716, 1989

    PubMed  Google Scholar 

  4. von Schoultz E, Lundblad D, Bergh J, Grankvist K, Henriksson R Estramustine binding protein and anti-proliferative effect of estramustine in human glioma cell lines Br J Cancer 58: 326–329, 1988

    PubMed  Google Scholar 

  5. Yoshida D, Piepmeier JM, Teramoto A In vitro inhibition of cell proliferation, viability, and invasiveness in U87MG human glioblastoma cells by estramustine phosphate Neurosurgery 39: 360–366, 1996

    Article  PubMed  CAS  Google Scholar 

  6. Bergenheim AT, Gunnarsson PO, Edman K, von Schoultz E, Hariz MI, Henriksson R Uptake and retention of estramustine and the presence of estramustine binding protein in malignant brain tumours in humans Br J Cancer 67: 358–361, 1993

    PubMed  CAS  Google Scholar 

  7. Vallbo C, Bergenheim T, Bergh A, Grankvist K, Henriksson R DNA fragmentation induced by the antimitotic drug estramustine in malignant rat glioma but not in normal brain – suggesting an apoptotic cell death Br J Cancer 71: 717–720, 1995

    PubMed  CAS  Google Scholar 

  8. Vallbo C, Bergenheim AT, Bergstrom P, Gunnarsson PO, Henriksson R Apoptotic tumor cell death induced by estramustine in patients with malignant glioma Clin Cancer Res 4: 87–91, 1998

    PubMed  CAS  Google Scholar 

  9. von Schoultz E, Lundgren E Henriksson R Effects of estramustine and its constituents on human malignant glioma cells Anticancer Res 10: 693–696, 1990

    PubMed  Google Scholar 

  10. Bergenheim AT, Henriksson R Pharmacokinetics and pharmacodynamics of estramustine phosphate Clin Pharmacokinet 34:163–172, 1998Review

    Article  PubMed  CAS  Google Scholar 

  11. Bergenheim AT, Zackrisson B, Elfverson J, Roos G, Henriksson R Radiosensitizing effect of estramustine in malignant glioma in vitro and in vivo J Neurooncol 23: 191–200, 1995

    Article  PubMed  CAS  Google Scholar 

  12. Johansson M, Bergenheim AT, Widmark A, Henriksson R: Effects of radiotherapy and estramustine on the microvasculature in malignant glioma Br J Cancer 80: 142–148, 1999

    Article  PubMed  CAS  Google Scholar 

  13. Kim JH, Khil MS, Kim SH, Ryu S, Gabel M Clinical and biological studies of estramustine phosphate as a novel radiation sensitizer Int J Radiat Oncol Biol Phys 15: 555–557, 1994

    Google Scholar 

  14. Yoshida D, Piepmeier J, Weinstein M Estramustine sensitizes human glioblastoma cells to irradiation Cancer Res 54:1415–1417,1994

    PubMed  CAS  Google Scholar 

  15. Landy H, Markoe A, Potter P, Lasalle G, Marini A, Savaraj N, Reis I, Heros D, Wangpaichitr M, Feun L Pilot study of estramustine added to radiosurgery and radiotherapy for treatment of high grade glioma J Neuro-Oncol 67: 215–220, 2004

    Article  Google Scholar 

  16. Aaronson NK, Ahmedzai S, Bergman B, Bullinger M, Cull A, Duez NJ, Filiberti A, Flechtner H, Fleishman SB, de Haes JC, et al. The European Organization for Research and Treatment of Cancer QLQ-C30: a quality-of-life instrument for use in international clinical trials in oncologyJ Natl Cancer Inst 85: 365–376, 1993

    Article  PubMed  CAS  Google Scholar 

  17. Fisher BJ, Scott C, Macdonald DR, Coughlin C, Curran WJ Phase I study of topotecan plus cranial radiation for glioblastoma multiforme: results of Radiation Therapy Oncology Group Trial 9507J Clin Oncol 19(4): 1111–1117, 2001

    PubMed  CAS  Google Scholar 

  18. Del Rowe J, Scott C, Werner-Wasik M, Bahary JP, Curran WJ, Urtasun RC, Fisher B Single-arm, open-label phase II study of intravenously administered tirapazamine and radiation therapy for glioblastoma multiformeJ Clin Oncol18: 1254–1259, 2000

    PubMed  CAS  Google Scholar 

  19. Kleinberg L, Grossman SA, Piantadosi S, Zeltzman M, Wharam M The effects of sequential versus concurrent chemotherapy and radiotherapy on survival and toxicity in patients with newly diagnosed high-grade astrocytomaInt J Radiat Oncol Biol Phys 44: 535–543, 1999

    Article  PubMed  CAS  Google Scholar 

  20. Piepmeier JM, Keefe DL, Weinstein MA, Yoshida D, Zielinski J, Lin TT, Chen Z, Naftolin F Estramustine and estrone analogs rapidly and reversibly inhibit deoxyribonucleic acid synthesis and alter morphology in cultured human glioblastoma cellsNeurosurgery 32: 422–430;1993 discussion 430–431

    Article  PubMed  CAS  Google Scholar 

  21. Kallio M, Sankila R, Jaaskelainen J, Karjalainen S, Hakulinen T A population-based study on the incidence and survival rates of 3857 glioma patients diagnosed from 1953 to 1984 Cancer 68: 1394–1400, 1991

    Article  PubMed  CAS  Google Scholar 

  22. Kayser-Gatchalian MC, Kayser K Thrombosis and intracranial tumorsJ Neurol 209: 217–224, 1975

    Article  PubMed  CAS  Google Scholar 

  23. Hamilton MG, Hull RD, Pineo GF Prophylaxis of venous thromboembolism in brain tumor patients J Neurooncol 22: 111–126, 1994

    Article  PubMed  CAS  Google Scholar 

  24. Marras LC, Geerts WH, Perry JR The risk of venous thromboembolism is increased throughout the course of malignant glioma: an evidence-based review Cancer 89: 640–646, 2000

    Article  PubMed  CAS  Google Scholar 

  25. von Schoultz E, Bergenheim T, Grankvist K, Henriksson R Estramustine binding protein in human brain-tumor tissue J␣Neurosurg 74: 962–964, 1991

    Google Scholar 

  26. Fluchter SH, Nelde HJ, Bjork P, Muntzing J, Bichler KH Effect of treatment on the expression of estramustine-binding protein (EMBP) in prostatic cancer patients: an immunohistochemical study Prostate 14: 27–43, 1989

    Article  PubMed  CAS  Google Scholar 

  27. Walz PH, Bjork P, Gunnarsson PO, Edman K, Hartley-Asp B Differential uptake of estramustine phosphate metabolites and its correlation with the levels of estramustine binding protein in prostate tumor tissue Clin Cancer Res4: 2079–2084, 1989

    Google Scholar 

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Acknowledgements

The support in the initiation of the study by Eeva Nordman, Department of Oncology, University Hospital, Åbo, Finland and the administrative support by Monica Sandström, Department of Oncology, University Hospital, Umeå, Sweden are gratefully acknowledged.

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Correspondence to Roger Henriksson.

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Henriksson, R., Malmström, A., Bergström, P. et al. High-grade astrocytoma treated concomitantly with estramustine and radiotherapy. J Neurooncol 78, 321–326 (2006). https://doi.org/10.1007/s11060-005-9106-9

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  • DOI: https://doi.org/10.1007/s11060-005-9106-9

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