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RNOP-09: Pegylated liposomal doxorubicine and prolonged temozolomide in addition to radiotherapy in newly diagnosed glioblastoma - a phase II study

Beier, Christoph P, Schmid, Christina, Gorlia, Thierry, Kleinletzenberger, Christine, Beier, Dagmar, Grauer, Oliver, Steinbrecher, Andreas, Hirschmann, Birgit, Brawanski, Alexander, Dietmaier, Christopher, Jauch-Worley, Tanja, Kölbl, Oliver, Pietsch, Torsten, Proescholdt, Martin, Rümmele, Petra, Muigg, Armin, Stockhammer, Günther, Hegi, Monika, Bogdahn, Ulrich, Hau, Peter·2009·BMC Cancer
DOI 10.1186/1471-2407-9-308PMC PMC2749868
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Abstract

Background: Although Temozolomide is effective against glioblastoma, the prognosis remains dismal and new regimens with synergistic activity are sought for. Methods: In this phase-I/II trial, pegylated liposomal doxorubicin (Caelyx™, PEG-Dox) and prolonged administration of Temozolomide in addition to radiotherapy was investigated in 63 patients with newly diagnosed glioblastoma. In phase-I, PEG-Dox was administered in a 3-by-3 dose-escalation regimen. In phase-II, 20 mg/m 2 PEG-Dox was given once prior to radiotherapy and on days 1 and 15 of each 28-day cycle starting 4 weeks after radiotherapy. Temozolomide was given in a dose of 75 mg/m 2 daily during radiotherapy (60 Gy) and 150-200 mg/m 2 on days 1-5 of each 28-day cycle for 12 cycles or until disease progression. Results: The toxicity of the combination of PEG-Dox, prolonged administration of Temozolomide, and radiotherapy was tolerable. The progression free survival after 12 months (PFS-12) was 30.2%, the median overall survival was 17.6 months in all patients including the ones from Phase-I. None of the endpoints differed significantly from the EORTC26981/NCIC-CE.3 data in a post-hoc statistical comparison. Conclusion: Together, the investigated combination is tolerable and feasible. Neither the addition of PEG-Dox nor the prolonged administration of Temozolomide resulted in a meaningful improvement of the patient's outcome as compared to the EORTC26981/NCIC-CE.3 data Trial registration: clinicaltrials.gov NCT00944801.

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  • Phase I/II trials with pegylated liposomal doxorubicin have shown that the drug has very few side effects and is well tolerated, but does not offer a significant advantage in overall survival or progression-free survival compared to standard protocols.

    “Phase I/II trials with pegylated liposomal doxorubicin have shown that the drug has very few side effects and is well tolerated, but does not offer a significant advantage in terms of overall survival or progression-free survival in comparison to the standard protocols based on radio-chemotherapy (Glas et al., 2007;Beier et al., 2009;Ananda et al., 2011).”

    From The association of statins plus LDL receptor‐targeted liposome‐encapsulated doxorubicin increases in vitro drug delivery across blood–brain barrier cells (2012) · cites this paper as Beier et al., 2009

    The Results (Activity of the combination regimen; page not provided) find no statistically significant improvement in progression-free or overall survival versus the historical radio-chemotherapy control. The Discussion calls overall toxicity acceptable, but the Results (Toxicity of the combination regimen) report cutaneous effects in almost all patients and substantial hematologic toxicity, so “very few side effects” overstates the findings. The trial tested PEG-Dox as part of a combination regimen, not the drug alone. (LLM, conf=0.90)

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  • The effects of pegylated liposomal doxorubicin (Doxil or Caelyx) in glioblastoma are unconvincing.

    “The effects of a pegylated liposomal doxorubicin (Doxil or Caelyx) have recently been investigated in glioblastoma, but the results obtained are unconvincing (Glas et al., 2007;Beier et al., 2009;Ananda et al., 2011).”

    From The association of statins plus LDL receptor‐targeted liposome‐encapsulated doxorubicin increases in vitro drug delivery across blood–brain barrier cells (2012) · cites this paper as Beier et al., 2009

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Research works printed but not linked: 25

  1. Wong ET, Hess KR, Gleason MJ, Jaeckle KA, Kyritsis AP, Prados MD, Levin VA, Yung WK: Outcomes and prognostic factors in recurrent glioma patients enrolled onto phase II clinical trials. J Clin Oncol. 1999, 17: 2572-2578. · DOI · Paper page
  2. Stupp R, Mason WP, Bent van den MJ, Weller M, Fisher B, Taphoorn MJ, Belanger K, Brandes AA, Marosi C, Bogdahn U, et al: Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N Engl J Med. 2005, 352: 987-996. 10.1056/NEJMoa043330. · DOI · Paper page
  3. Beier D, Rohrl S, Pillai DR, Schwarz S, Kunz-Schughart LA, Leukel P, Proescholdt M, Brawanski A, Bogdahn U, Trampe-Kieslich A, et al: Temozolomide preferentially depletes cancer stem cells in glioblastoma. Cancer Res. 2008, 68: 5706-5715. 10.1158/0008-5472.CAN-07-6878. · DOI
  4. Hegi ME, Diserens AC, Gorlia T, Hamou MF, de Tribolet N, Weller M, Kros JM, Hainfellner JA, Mason W, Mariani L, et al: MGMT gene silencing and benefit from temozolomide in glioblastoma. N Engl J Med. 2005, 352: 997-1003. 10.1056/NEJMoa043331. · DOI · Paper page
  5. Wolff JE, Trilling T, Molenkamp G, Egeler RM, Jurgens H: Chemosensitivity of glioma cells in vitro: a meta analysis. J Cancer Res Clin Oncol. 1999, 125: 481-486. 10.1007/s004320050305. · DOI
  6. Neuwelt EA, Pagel M, Barnett P, Glassberg M, Frenkel EP: Pharmacology and toxicity of intracarotid adriamycin administration following osmotic blood-brain barrier modification. Cancer Res. 1981, 41: 4466-4470.
  7. Siegal T, Horowitz A, Gabizon A: Doxorubicin encapsulated in sterically stabilized liposomes for the treatment of a brain tumor model: biodistribution and therapeutic efficacy. J Neurosurg. 1995, 83: 1029-1037. 10.3171/jns.1995.83.6.1029. · DOI · Paper page
  8. Harris L, Batist G, Belt R, Rovira D, Navari R, Azarnia N, Welles L, Winer E: Liposome-encapsulated doxorubicin compared with conventional doxorubicin in a randomized multicenter trial as first-line therapy of metastatic breast carcinoma. Cancer. 2002, 94: 25-36. 10.1002/cncr.10201. · DOI
  9. Cabanes A, Tzemach D, Goren D, Horowitz AT, Gabizon A: Comparative study of the antitumor activity of free doxorubicin and polyethylene glycol-coated liposomal doxorubicin in a mouse lymphoma model. Clin Cancer Res. 1998, 4: 499-505.
  10. Fabel K, Dietrich J, Hau P, Wismeth C, Winner B, Przywara S, Steinbrecher A, Ullrich W, Bogdahn U: Long-term stabilization in patients with malignant glioma after treatment with liposomal doxorubicin. Cancer. 2001, 92: 1936-1942. 10.1002/1097-0142(20011001)92:7<1936::AID-CNCR1712>3.0.CO;2-H. · DOI
  11. Hau P, Fabel K, Baumgart U, Rummele P, Grauer O, Bock A, Dietmaier C, Dietmaier W, Dietrich J, Dudel C, et al: Pegylated liposomal doxorubicin-efficacy in patients with recurrent high-grade glioma. Cancer. 2004, 100: 1199-1207. 10.1002/cncr.20073. · DOI
  12. Chua SL, Rosenthal MA, Wong SS, Ashley DM, Woods AM, Dowling A, Cher LM: Phase 2 study of temozolomide and Caelyx in patients with recurrent glioblastoma multiforme. Neuro Oncol. 2004, 6: 38-43. 10.1215/S1152851703000188. · DOI
  13. Glas M, Koch H, Hirschmann B, Jauch T, Steinbrecher A, Herrlinger U, Bogdahn U, Hau P: Pegylated liposomal doxorubicin in recurrent malignant glioma: analysis of a case series. Oncology. 2007, 72: 302-307. 10.1159/000113052. · DOI · Paper page
  14. Hau P, Koch D, Hundsberger T, Marg E, Bauer B, Rudolph R, Rauch M, Brenner A, Rieckmann P, Schuth J, et al: Safety and feasibility of long-term temozolomide treatment in patients with high-grade glioma. Neurology. 2007, 68: 688-690. 10.1212/01.wnl.0000255937.27012.ee. · DOI
  15. Vlassenbroeck I, Califice S, Diserens AC, Migliavacca E, Straub J, Di Stefano I, Moreau F, Hamou MF, Renard I, Delorenzi M, et al: Validation of real-time methylation-specific PCR to determine O6-methylguanine-DNA methyltransferase gene promoter methylation in glioma. J Mol Diagn. 2008, 10: 332-337. 10.2353/jmoldx.2008.070169. · DOI
  16. Vail DM, Chun R, Thamm DH, Garrett LD, Cooley AJ, Obradovich JE: Efficacy of pyridoxine to ameliorate the cutaneous toxicity associated with doxorubicin containing pegylated (Stealth) liposomes: a randomized, double-blind clinical trial using a canine model. Clin Cancer Res. 1998, 4: 1567-1571.
  17. Grant R, Liang BC, Slattery J, Greenberg HS, Junck L: Chemotherapy response criteria in malignant glioma. Neurology. 1997, 48: 1336-1340. · DOI
  18. Remlinger KA: Cutaneous reactions to chemotherapy drugs: the art of consultation. Arch Dermatol. 2003, 139: 77-81. 10.1001/archderm.139.1.77. · DOI
  19. Lyass O, Uziely B, Ben-Yosef R, Tzemach D, Heshing NI, Lotem M, Brufman G, Gabizon A: Correlation of toxicity with pharmacokinetics of pegylated liposomal doxorubicin (Doxil) in metastatic breast carcinoma. Cancer. 2000, 89: 1037-1047. 10.1002/1097-0142(20000901)89:5<1037::AID-CNCR13>3.0.CO;2-Z. · DOI
  20. Koukourakis MI, Koukouraki S, Fezoulidis I, Kelekis N, Kyrias G, Archimandritis S, Karkavitsas N: High intratumoural accumulation of stealth liposomal doxorubicin (Caelyx) in glioblastomas and in metastatic brain tumours. Br J Cancer. 2000, 83: 1281-1286. 10.1054/bjoc.2000.1459. · DOI
  21. Gabizon A, Martin F: Polyethylene glycol-coated (pegylated) liposomal doxorubicin. Rationale for use in solid tumours. Drugs. 1997, 54 (Suppl 4): 15-21. 10.2165/00003495-199700544-00005. · DOI
  22. Herrlinger U, Rieger J, Koch D, Loeser S, Blaschke B, Kortmann RD, Steinbach JP, Hundsberger T, Wick W, Meyermann R, et al: Phase II trial of lomustine plus temozolomide chemotherapy in addition to radiotherapy in newly diagnosed glioblastoma: UKT-03. J Clin Oncol. 2006, 24: 4412-4417. 10.1200/JCO.2006.06.9104. · DOI
  23. Wick A, Felsberg J, Steinbach JP, Herrlinger U, Platten M, Blaschke B, Meyermann R, Reifenberger G, Weller M, Wick W: Efficacy and tolerability of temozolomide in an alternating weekly regimen in patients with recurrent glioma. J Clin Oncol. 2007, 25: 3357-3361. 10.1200/JCO.2007.10.7722. · DOI
  24. Chinot OL, Barrie M, Fuentes S, Eudes N, Lancelot S, Metellus P, Muracciole X, Braguer D, Ouafik L, Martin PM, et al: Correlation between O6-methylguanine-DNA methyltransferase and survival in inoperable newly diagnosed glioblastoma patients treated with neoadjuvant temozolomide. J Clin Oncol. 2007, 25: 1470-1475. 10.1200/JCO.2006.07.4807. · DOI
  25. Reardon DA, Nabors LB, Stupp R, Mikkelsen T: Cilengitide: an integrin-targeting arginine-glycine-aspartic acid peptide with promising activity for glioblastoma multiforme. Expert Opin Investig Drugs. 2008, 17: 1225-1235. 10.1517/13543784.17.8.1225. · DOI

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Metadata

Authors
Beier, C. P., Schmid, C., Gorlia, T., Kleinletzenberger, C., Beier, D., Grauer, O., Steinbrecher, A., Hirschmann, B., Brawanski, A., Dietmaier, C., Jauch-Worley, T., Kölbl, O., Pietsch, T., Proescholdt, M., Rümmele, P., Muigg, A., Stockhammer, G., Hegi, M., Bogdahn, U., & Hau, P.
Venue
BMC Cancer
Publisher
Springer Science and Business Media LLC
Published
2009-09-02
Volume
9
Issue
1
ISSN
1471-2407
DOI
10.1186/1471-2407-9-308
PMC
PMC2749868
Cited by
125
References
1
Language
en
Licence
www.springer.com/tdm (unspecified)

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