Abstract
Glioblastoma is a highly angiogenic tumor with a dismal prognosis. Continuous oral low-dose chemotherapy with methotrexate (MTX) and cyclophosphamide (CPM) has modest activity in heavily pretreated patients with breast cancer. We explored the efficacy of 100 mg CPM daily and 5 mg MTX twice weekly in relapsed glioblastoma. Ten patients, 22–59 years old, with a Karnofsky score of 50% or higher who had failed at least two chemotherapies were accrued. No toxicity was observed. No patient showed a complete or partial response. Five of 10 patients progressed within 2 months of therapy. Another five patients progressed after 3–4.5 months. The median time to progression was 2.5 months. The median overall survival after start of MTX/CPM was 6.9 months (range 0.5–18.8 months). Since the progression-free survival rate at 6 months was 0%, the trial was prematurely closed.
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ET Wong KR Hess MJ Gleason KA Jaeckle AP Kyritsis MD Prados VA Levin WK Yung (1999) ArticleTitleOutcomes and prognostic factors in recurrent glioma patients enrolled onto phase II clinical trials J Clin Oncol 17 2572–2578
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 multiforme at first relapse. Br J Cancer 83 588–593 Occurrence Handle10.1054/bjoc.2000.1316 Occurrence Handle1:CAS:528:DC%2BD3cXmvVCgsrs%3D Occurrence Handle10944597
HA Fine WD Figg K Jaeckle PY Wen AP Kyritsis JS Loeffler VA Levin PM Black R Kaplan JM Pluda WK Yung (2000) ArticleTitlePhase II trial of the antiangiogenic agent thalidomide in patients with recurrent high-grade gliomas J Clin Oncol 18 708–715
SC Short D Traish A Dowe F Hines M Gore M Brada (2001) ArticleTitleThalidomide as an anti-angiogenic agent in relapsed gliomas J Neurooncol 51 41–45
HA Fine PY Wen EA Maher E Viscosi T Batchelor N Lakhani WD Figg BW Purow CB Borkowf (2003) ArticleTitlePhase II trial of thalidomide and carmustine for patients with recurrent high-grade gliomas J Clin Oncol 21 2299–2304
T Browder CE Butterfield BM Kraling B Shi B Marshall MS O’Reilly J Folkman (2000) ArticleTitleAntiangiogenic scheduling of chemotherapy improves efficacy against experimental drug-resistant cancer Cancer Res 60 1878–1886 Occurrence Handle1:CAS:528:DC%2BD3cXisVynurk%3D Occurrence Handle10766175
G Klement S Baruchel J Rak S Man K Clark D Hicklin P Bohlen RS Kerbel (2000) ArticleTitleContinuous low-dose therapy with vinblastine and VEGF receptor-2 antibody induces sustained tumor regression without overt toxicity. J Clin Invest 105 R15–R24 Occurrence Handle1:CAS:528:DC%2BD3cXisFOlurc%3D Occurrence Handle10772661
ID Bassukas G Vester B Maurer-Schultze (1990) ArticleTitleCell kinetic studies of endothelial cells in the adenocarcinoma EO 771 and the effect of cyclophosphamide Virchows Arch B Cell Pathol 59 251–256
S Hirata T Matsubara R Saura H Tateishi K Hirohata (1989) ArticleTitleInhibition of in vitro vascular endothelial cell proliferation and in vivo neovascularization by low dose methotrexate Arthritis Rheum 32 1065–1073
M Iwahana N Utoguchi T Mayumi M Goryo K Okada (1998) ArticleTitleDrug resistance and P-glycoprotein expression in endothelial cells of newly formed capillaries induced by tumors. Anticancer Res 18 2977–2980
S Man G Bocci G Francia SK Green S Jothy D Hanahan P Bohlen DJ Hicklin G Bergers RS Kerbel (2002) ArticleTitleAntitumor effects in mice of low-dose (metronomic) cyclophosphamide administered continuously through the drinking water. Cancer Res 62 2731–2735 Occurrence Handle1:CAS:528:DC%2BD38XjvFSmsbg%3D Occurrence Handle12019144
KD Miller CJ Sweeney GW Sledge SuffixJr. (2001) ArticleTitleRedefining the target chemotherapeutics as antiangiogenics J Clin Oncol 19 1195–1206 Occurrence Handle1:CAS:528:DC%2BD3MXhvFertrY%3D Occurrence Handle11181686
S Gately R Kerbel (2001) ArticleTitleAntiangiogenic scheduling of lower dose cancer chemotherapy Cancer 7 427–436 Occurrence Handle1:STN:280:DC%2BD3Mnjs12jsQ%3D%3D Occurrence Handle11693902
M Colleoni A Rocca MT Sandri L Zorzino G Masci F Nole G Peruzzotti C Robertson L Orlando S Cinieri F De Braud G Viale A Goldhirsch (2002) ArticleTitleLow dose oral methotrexate and cyclophosphamide in metastatic breast cancer: antitumor activity and correlation with vascular endothelial growth factor levels Ann Oncol 13 73–80
DR Macdonald TL Cascino SC Schold SuffixJr. JG Cairncross (1990) ArticleTitleResponse criteria for phase II studies of supratentorial malignant glioma J Clin Oncol 8 1277–1280
InstitutionalAuthorNameThe Neuro-Oncology Working Group of the German Cancer Society (2003) ArticleTitleNeuro-Oncology Working Group 01 trial of nimustine plus teniposide versus nimustine pluscytarabine chemotherapy in addition to involved-field radiotherapy in the first-line treatment of malignant glioma J Clin Oncol 21 3276–3284
AF Mulne JM Ducore RD Elterman HS Friedman JP Krischer LE Kun JJ Shuster RP Kadota (2000) ArticleTitleOral methotrexate for recurrent brain tumors in children: a Pediatric Oncology Group study J Pediatr Hematol Oncol 22 41–44
P Hau U Baumgart K Pfeifer A Bock T Jauch J Dietrich K Fabel O Grauer C Wismeth M Klinkhammer-Schalke M Allgauer G Schuierer H Koch J Schlaier W Ulrich A Brawanski U Bogdahn A Steinbrecher (2003) ArticleTitleSalvage therapy in patients with glioblastoma: is there any benefit Cancer 98 2678–2686
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Herrlinger, U., Rieger, J., Steinbach, J.P. et al. UKT-04 trial of continuous metronomic low-dose chemotherapy with methotrexate and cyclophosphamide for recurrent glioblastoma. J Neurooncol 71, 295–299 (2005). https://doi.org/10.1007/s11060-004-1726-y
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DOI: https://doi.org/10.1007/s11060-004-1726-y