Skip to main content

Advertisement

SpringerLink
Log in

Systemic Temozolomide Combined with Loco-regional Mitoxantrone in Treating Recurrent Glioblastoma

  • Clinical Study
  • Published:
Journal of Neuro-Oncology Aims and scope Submit manuscript

Abstract

Twenty-two recurrent GBM patients were enrolled for second tumor debulking with local positioning of a Rickam reservoir, in order to locally deliver chemotherapy with the aim of controlling local tumor recurrence. We designed a protocol using systemic temozolomide (150 mg/sqm days 1–5 every 28) in association with mitoxantrone, delivered through the reservoir (4 mg/day 1–5 every 28) positioned into the area of tumor exeresis. After re-operation a residual tumor mass no larger than 2 cm was identified in 18/22 patients. The patients were treated with monthly cycles of chemotherapy until evolution of the tumor, but in no case for more than 10 cycles. Responses were evaluated by MRI scans performed every 2 months and images assessed according to MacDonald’s criteria. Response rate: no complete responses (CR), 5 partial responses (PR), 13 stable disease (SD) and 4 progressive disease (PD) occurred. The median progression-free survival (PFS) and survival time (ST) of the whole group of treated patients was 7 and 11 months, respectively and more than a quarter of the patients survived over 18 months. During the study, the patients’ compliance was complete and no dropouts occurred. Hematological toxicity was mild and after repeated local injections only minor neurological side-effects occurred. Despite some bias in patients’ selection not excluded in this pilot study, results are interesting: the PFS was as long as the survival of recurrent GBM reported in the literature.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. M Huncharek J Muscat (1998) ArticleTitleTreatment of recurrent high grade astrocytoma: results of a systematic review of 1415 patients Anticancer Res 18 1303–1312 Occurrence Handle9615807

    PubMed  Google Scholar 

  2. PL Kornblith M Walker (1998) ArticleTitleChemotherapy for malignant gliomas J Neurosurg 68 1–17

    Google Scholar 

  3. MD Walker SB Green DP Byar E Alexander SuffixJr U Batzdorf WH Brooks WE Hunt CS McCarty MS Mahavley SuffixJr J Mealey G Owens J Ransohoff JT Robertson (1980) ArticleTitleRandomized comparisons of radiotherapy and nitrosoureas for the treatment of malignant glioma after surgery N Engl J Med 303 1323–1327 Occurrence Handle7001230

    PubMed  Google Scholar 

  4. HA Fine KBG Dear YS Loeffler PML Black GP Canellos (1993) ArticleTitleMeta-analysis of radiation therapy with and without adjuvant chemotherapy for malignant gliomas in adults Cancer 71 2585–2597 Occurrence Handle8453582

    PubMed  Google Scholar 

  5. WK Yung RE Albright J Olson R Fredericks K Fink MD Prados M Brada A Spence RJ Hohl W Shapiro M Glantz H Greenberg RG Selker NA Vick R Rampling H Friedman P Phillips J Bruner N Yue D Osoba S Zaknoen VA Levin (2000) ArticleTitleA phase II study of temozolomide vs. procarbazine in patients with glioblastoma multiforne at first relapse Br J Cancer 83 588–593 Occurrence Handle10.1054/bjoc.2000.1316 Occurrence Handle10944597

    Article  PubMed  Google Scholar 

  6. D Osoba M Brada MD Prados WK Yung (2000) ArticleTitleEffect of disease burden on health-related quality of life in patients with malignant gliomas Neuro-oncol 4 221–228 Occurrence Handle10.1215/S1522851799000551

    Article  Google Scholar 

  7. M Brada K Hoang-Xuan R Rampling PY Dietrich LY Dirix D MacDonald JJ Heimans BA Zonnenberg JM Bravo-Marques R Henriksson R Stupp N Yue J Bruner M Dugan S Rao S Zaknoen (2001) ArticleTitleMulticenter phase II trial of temozolomide in patients with glioblastoma multiforme at first relapse Ann Oncol 12 149–150 Occurrence Handle10.1023/A:1008382516636 Occurrence Handle11300316

    Article  PubMed  Google Scholar 

  8. DR McDonald (2001) ArticleTitleTemozolomide for recurrent high-grade glioma Semin Oncol 4 3–12

    Google Scholar 

  9. L Sipos D Vitanovics D Afra (2001) ArticleTitleTreatment of recidive malignant gliomas with temozolomide Ann Oncol 12 259–266 Occurrence Handle10.1023/A:1008382516636 Occurrence Handle11300335

    Article  PubMed  Google Scholar 

  10. A Gaya J Rees A Greenstein J Stebbing (2002) ArticleTitleThe use of temozolomide in recurrent malignant gliomas Cancer Treat Rev 28 115–120 Occurrence Handle10.1053/ctrv.2002.0261 Occurrence Handle12297119

    Article  PubMed  Google Scholar 

  11. S Trent A Kong SC Short D Traish S Ashley A Dowe F Hines M Brada (2002) ArticleTitleTemozolomide as second-line chemotherapy for relapsed gliomas J Neurooncol 57 247–251 Occurrence Handle10.1023/A:1015788814667 Occurrence Handle12125988

    Article  PubMed  Google Scholar 

  12. M Prados (2001) ArticleTitleTemozolomide in combination with other cytotoxic agents Semin Oncol 28 24–33 Occurrence Handle10.1016/S0093-7754(01)90068-5

    Article  Google Scholar 

  13. ES Newlands T Foster S Zaknoen (2003) ArticleTitlePhase I study of temozolamide (TMZ) combined with procarbazine (PCB) in patients with gliomas Br J Cancer 21 248–251 Occurrence Handle10.1038/sj.bjc.6601043

    Article  Google Scholar 

  14. DN Korones M Benita-Weiss TE Coyle L Mechtler P Bushunow B Evans DA Reardon JA Quinn H Friedman (2003) ArticleTitlePhase I study of temozolomide and escalating doses of oral etoposide for adults with recurrent malignant glioma Cancer 97 1963–1968 Occurrence Handle10.1002/cncr.11260 Occurrence Handle12673724

    Article  PubMed  Google Scholar 

  15. MD Groves VK Puduvalli KR Hess KA Jaeckle P Peterson WK Yung VA Levin (2002) ArticleTitlePhase II trial of temozolomide plus the matrix metalloproteinase inhibitor, marimastat, in recurrent and progressive glioblastoma multiforme Clin Oncol 20 1383–1388 Occurrence Handle10.1200/JCO.20.5.1383

    Article  Google Scholar 

  16. AW Tolcher SL Gerson L Denis C Geyer LA Hammond A Patnaik AD Goetz G Schwartz T Edwards L Reyderman P Statkevich DL Cutler EK Rowinsky (2003) ArticleTitleMarked inactivation of O6-alkylguanine-DNA alkyltransferase activity with protracted temozolomide schedules Br J Cancer 88 1004–1011 Occurrence Handle10.1038/sj.bjc.6600827 Occurrence Handle12671695

    Article  PubMed  Google Scholar 

  17. RB Khan JJ Raizer MG Malkin KA Bazylewicz LE Abrey (2002) ArticleTitleA phase II study of extended low-dose temozolomide in recurrent malignant gliomas Neuro-oncol 4 39–43 Occurrence Handle10.1215/S1522851701000382 Occurrence Handle11772431

    Article  PubMed  Google Scholar 

  18. M Esteller SR Hamilton PC Burger SB Baylin JG Herman (1999) ArticleTitleInactivation of the DNA repair gene O6-methylguanine-DNA methyltransferase by promoter hypermethylation is a common event in primary human neoplasia Cancer Res 59 793–797 Occurrence Handle10029064

    PubMed  Google Scholar 

  19. M Nakamura T Watanabe Y Yonekawa P Kleihues H Ohgaki (2001) ArticleTitlePromoter methylation of the DNA repair gene MGMT in astrocytomas is frequently associated with G:C –> A:T mutations of the TP53 tumor suppressor gene Carcinogenesis 22 1715–1719 Occurrence Handle10.1093/carcin/22.10.1715 Occurrence Handle11577014

    Article  PubMed  Google Scholar 

  20. S Gururangan L Cokgor JN Rich S Edwards ML Affronti JA Quinn JE Herndon Suffix2nd JM Provenzale RE McLendon S Tourt-Uhlig JH Sampson V Stafford-Fox S Zaknoen M Early AH Friedman HS Friedman (2001) ArticleTitlePhase I study of Gliadel wafers plus temozolomide in adults with recurrent supratentorial high-grade gliomas Neuro-oncol 3 246–250 Occurrence Handle10.1215/S1522851700000703 Occurrence Handle11584894

    Article  PubMed  Google Scholar 

  21. A Boiardi A Silvani AL Pozzi L Fariselli G Broggi G Salmaggi (1999) ArticleTitleInterstitial chemotherapy plus systemic chemotherapy for glioblastoma patients: improved survival in sequential studies J Neuroncol 41 151–157 Occurrence Handle10.1023/A:1006119505170

    Article  Google Scholar 

  22. A Boiardi M Eoli A Salmaggi B Zappacosta L Fariselli I Milanesi G Broggi A Silvani (2001) ArticleTitleEfficacy of intratumoral delivery of mitoxantrone in recurrent malignant glial tumours J Neurooncol 54 39–47 Occurrence Handle10.1023/A:1012510513780 Occurrence Handle11763421

    Article  PubMed  Google Scholar 

  23. DR MacDonald TL Cascino S Clifford (1990) ArticleTitleResponse criteria for phase II studies of supratentorial malignant glioma J Clin Oncol 8 1277–1280 Occurrence Handle2358840

    PubMed  Google Scholar 

  24. Bissola L, Eoli M, Silvani A, Polio B, Bianchissi D, Manghi F, Boiardi A, Finocchiaro G: MGMT promoter hypermethylation is more frequent in secondary GBM and is independent from other prognostic factor. Proceedings of the American association for Cancer research 95. Annual meeting 2004. Orlando, FL

  25. EL Kaplan P Meier (1958) ArticleTitleNonparametric estimation from incomplete observations J Am Stat Assoc 53 457–481

    Google Scholar 

  26. MM Oken RH Creech DC Tormey J Horton TE Davis ET McFadden PP Carbone (1982) ArticleTitleToxicity and response criteria of the Eastern Cooperative Oncology Group Am J Clin Oncol 5 649–655 Occurrence Handle7165009

    PubMed  Google Scholar 

  27. MR Gilbert JG Supko T Batchelor G Lesser JD Fisher S Piantadosi S Grossman (2003) ArticleTitlePhase I clinical and pharmacokinetic study of irinotecan in adults with recurrent malignant glioma Clin Cancer Res 9 2940–2949 Occurrence Handle12912940

    PubMed  Google Scholar 

  28. Ermani M, Brandes A, Pasetto LM, Basso U, Reni M, Turazzi S, Berlucchi S, Ruzzolino P, Pinna G, Scienza R. Monfardini S, First line chemotherapy with cisplatin plus fractionated temozolomide [bid] in recurrent glioblastoma (GBM). Annual Meeting ASCO abs 2076. Orlando, 2000

  29. DN Korones M Benita-Weiss TE Coyle L Mechtler P Bushunow B Evans DA Reardon JA Quinn H Friedman (2003) ArticleTitlePhase I study of temozolomide and escalating doses of oral etoposide for adults with recurrent malignant glioma Cancer 15 1963–1968 Occurrence Handle10.1002/cncr.11260

    Article  Google Scholar 

  30. H Brem S Piantadossi P Burger M Walker RW Seiler (1995) ArticleTitlePlacebo controlled trial of safety and efficacy of intraoperative controlled delivery by biodegradable polymers of chemotherapy for recurrent gliomas. The polymer-brain Tumor Treatment Group Lancet 345 1008–1012 Occurrence Handle10.1016/S0140-6736(95)90755-6 Occurrence Handle7723496

    Article  PubMed  Google Scholar 

  31. S Valtonen U Timonen P Toivanen H Kalimo L Kivipelto O Heiskanen G Usgaard T Kuurne (1997) ArticleTitleInterstitial chemotherapy with carmustine-loaded polymers for high-grade gliomas: a randomized double-blind study Neurosurgery 41 44–49 Occurrence Handle10.1097/00006123-199707000-00011 Occurrence Handle9218294

    Article  PubMed  Google Scholar 

  32. EP Sipos B Tyler S Piantadosi PC Burger H Brem (1997) ArticleTitleOptimizing interstitial delivery of BCNU from controlled release polymers for the treatment of brain tumors Cancer Chemother Pharmacol 39 383–389 Occurrence Handle10.1007/s002800050588 Occurrence Handle9054951

    Article  PubMed  Google Scholar 

  33. P Perego A Boiardi N Carenini M Cesare ParticleDe E Dolfini R Giardino I Magnani A Silvani C Soranzo (1994) ArticleTitleCharacterisation of an established human maligant glioblastoma cell line and its response to conventional garugs J Cancer Res Clin Oncol 120 585–592 Occurrence Handle10.1007/BF01212812 Occurrence Handle7929529

    Article  PubMed  Google Scholar 

  34. JP Jordan CM Hand RS Markowitz P Black (1992) ArticleTitleTest for chemotherapeutic sensitivity of cerebral gliomas: use of colorimetric MTT assay J Neurooncol 14 19–35 Occurrence Handle10.1007/BF00170942 Occurrence Handle1335043

    Article  PubMed  Google Scholar 

  35. G Nikkhah JC Tonn O Hoffmann HP Kraemer JL Darling W Schachenmayr R Schonmayr (1992) ArticleTitleThe MTT assay for chemosensitivity testing of human tumors of the central nervous system. Part II: Evaluation of patient- and drug-specific variables J Neurooncol 13 13–24 Occurrence Handle1613536

    PubMed  Google Scholar 

  36. M Senkal JC Tonn R Schonmayr W Schachenmayr U Eickhoff M Kelnen E Kollig (1997) ArticleTitleMitoxantrone-induced DNA strand breaks in cell-cultures of malignant human astrocytoma and glioblastoma tumors J Neurooncol 32 203–208 Occurrence Handle10.1023/A:1005792410604 Occurrence Handle9049881

    Article  PubMed  Google Scholar 

  37. RM Green DJ Stewart H Hugenholtz MT Richard M Thibault V Montpetit (1986) ArticleTitleHuman central nervous system and plasma pharmacology of mitoxantrone J Neurooncol 6 75–83 Occurrence Handle10.1007/BF00163544

    Article  Google Scholar 

  38. JE Wolff T Trilling G Molenkamp RM Egeler H Jurgens (1999) ArticleTitleChemosensitivity of glioma cells in vitro: a meta analysis J Cancer Res Clin Oncol 125 481–486 Occurrence Handle10.1007/s004320050305 Occurrence Handle10480340

    Article  PubMed  Google Scholar 

  39. DJ Stewart RM Green NZ Mikhael V Montpetit M Thibault JA Maroun (1986) ArticleTitleHuman autopsy tissue concentrations of mitoxantrone Cancer Treat Rep 70 1255–1261 Occurrence Handle3768871

    PubMed  Google Scholar 

  40. F Di Meco KW Li BM Tyler AS Wolf H Brem A Olivi (2002) ArticleTitleLocal delivery of mitoxantrone for the treatment of malignant brain tumors in rats J Neurosurg 5 1173–1178

    Google Scholar 

  41. RA Kroll MA Pagel LL Muldoon S Roman-Goldstein E Neuwelt (1996) ArticleTitleIncreasing volume of distribution to the brain with interstitial infusion: dose, rather than convection, might be the most important factor Neurosurgery 38 746–753 Occurrence Handle10.1097/00006123-199604000-00024 Occurrence Handle8692395

    Article  PubMed  Google Scholar 

  42. G Broggi P Ferroli A Franzini A Silvani A Salmaggi M Eoli A Boiardi (2003) ArticleTitleLocal delivery of mitoxantrone for the treatment of malignant brain tumors in rats J Neurosurg 98 935–936 Occurrence Handle12691429

    PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Neuro-Oncology, Istituto Nazionale Neurologico “Carlo Besta”, Italy

    A. Boiardi, M. Eoli, A. Salmaggi, E. Lamperti, A. Botturi & A. Silvani

  2. Department of Neurosurgery, Istituto Nazionale Neurologico “Carlo Besta”, Italy

    G. Broggi

  3. Unit of Experimental Neuro-Oncology and Gene Therapy, Istituto Nazionale Neurologico “Carlo Besta”, Milano, Italy

    L. Bissola & G. Finocchiaro

Authors
  1. A. Boiardi
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. M. Eoli
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. A. Salmaggi
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. E. Lamperti
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. A. Botturi
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. G. Broggi
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. L. Bissola
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. G. Finocchiaro
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. A. Silvani
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to A. Boiardi.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Boiardi, A., Eoli, M., Salmaggi, A. et al. Systemic Temozolomide Combined with Loco-regional Mitoxantrone in Treating Recurrent Glioblastoma. J Neurooncol 75, 215–220 (2005). https://doi.org/10.1007/s11060-005-3030-x

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11060-005-3030-x

Keywords

Search

Navigation