Low-dose chemotherapy in combination with COX-2 inhibitors and PPAR-gamma agonists in recurrent high-grade gliomas - a phase II study.
OBJECTIVE
Combined treatment approaches targeting tumor as well as other cells contributing to tumor progression may control chemorefractory malignancies.


METHODS
A phase II trial was initiated to analyze the activity of continuously administered pioglitazone and rofecoxib combined with low-dose chemotherapy (capecitabine or temozolomide) in patients with high-grade gliomas (glioblastoma or anaplastic glioma).


RESULTS
Fourteen patients were evaluable for response and toxicity. Major side effects were palmoplantar erythema, edema and motor neuropathy grade 3. Disease stabilizations lasting longer than 3 months were noted in 4 of 14 patients (29%). Clinical responses did not correspond to immunohistochemical staining for cyclooxygenase 2, peroxisome proliferator-activated receptor-gamma and CD31.


CONCLUSIONS
The study demonstrates that this novel regimen is moderately active and well tolerated in patients with high-grade gliomas. As a comparably small proportion of patients responded, the regimen might only be suitable for a subset of highly selected patients.
Hau
P
P
OncoRay/ZIK Dresden, Dresden, Germany. peter.hau@medbo.de
Kunz-Schughart
L
L
Bogdahn
U
U
Baumgart
U
U
Hirschmann
B
B
Weimann
E
E
Muhleisen
H
H
Ruemmele
P
P
Steinbrecher
A
A
Reichle
A
A
D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects; D001932:Brain Neoplasms / Q000098:blood supply / Q000737:chemistry / Q000188:drug therapy* / Q000473:pathology*; D000069287:Capecitabine; D052246:Cyclooxygenase 2 Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D003606:Dacarbazine / Q000008:administration & dosage / Q000031:analogs & derivatives; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D004334:Drug Administration Schedule; D004487:Edema / Q000139:chemically induced; D004525:Efferent Pathways / Q000187:drug effects; D004890:Erythema / Q000139:chemically induced; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000031:analogs & derivatives; D015972:Gene Expression Regulation, Neoplastic; D005909:Glioblastoma / Q000188:drug therapy; D005910:Glioma / Q000098:blood supply / Q000737:chemistry / Q000188:drug therapy* / Q000473:pathology*; D006801:Humans; D007150:Immunohistochemistry; D007783:Lactones / Q000008:administration & dosage; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy* / Q000473:pathology; D009389:Neovascularization, Pathologic / Q000517:prevention & control; D047495:PPAR gamma / Q000819:agonists*; D000077205:Pioglitazone; D011237:Predictive Value of Tests; D011788:Quality of Life; D013450:Sulfones / Q000008:administration & dosage; D000077204:Temozolomide; D045162:Thiazolidinediones / Q000008:administration & dosage; D016896:Treatment Outcome
D052246:Cyclooxygenase 2 Inhibitors; D007783:Lactones; D047495:PPAR gamma; D013450:Sulfones; D045162:Thiazolidinediones; C116926:rofecoxib; D003841:Deoxycytidine; D000069287:Capecitabine; D003606:Dacarbazine; D005472:Fluorouracil; D000077205:Pioglitazone; D000077204:Temozolomide