alitretinoin and Glioblastoma

In this article we report the results of a study of the relationship between response and progression in 375 patients with recurrent glioma enrolled in phase II chemotherapy trials. We reviewed the records of patients from 8 consecutive phase II trials, including 225 patients with recurrent glioblastoma multiforme and 150 with recurrent anaplastic astrocytoma. Median age was 45 years (range, 15-82) and median Karnofsky performance score was 80 (range, 60-100). Forty-one patients (11%) had more than two prior resections and/or more than two prior chemotherapy regimens. Best response was complete (n = 1) or partial (n = 33) in 34 patients (9%). Median time to response was 14 weeks, and median response duration was 44 weeks. Simon-Makuch estimates for 52-week progression-free survival for patients progression-free at 13 weeks were 48% for response and 28% for nonresponse. When response was treated as a time-dependent covariate in a Cox proportional hazards regression analysis, response was associated with significantly lower failure rates (hazard ratio 0.5; 95% confidence interval 0.3-0.8; P = 0.0016). This study showed that response in recurrent glioma is associated with a significant reduction in progression rates.

Topics: Actuarial Analysis; Adolescent; Adult; Aged; Aged, 80 and over; Alitretinoin; Antineoplastic Combined Chemotherapy Protocols; Astrocytoma; Brain Neoplasms; Carboplatin; Combined Modality Therapy; Disease Progression; Disease-Free Survival; Eflornithine; Female; Fluorouracil; Glioblastoma; Glioma; Humans; Interferon-beta; Male; Menogaril; Middle Aged; Neoplasm Recurrence, Local; Procarbazine; Prognosis; Proportional Hazards Models; Texas; Treatment Outcome; Tretinoin

We investigated the effect of the peroxisomal proliferator (PP) perfluorodecanoic acid (PFDA), alone or in combination with 9-cis-retinoic acid (RX) on the human glioblastoma cell line Lipari (LI). Cell proliferation, apoptotic rate, peroxisome morphology and morphometry, peroxisomal enzyme activities and the presence of peroxisome proliferator-activated receptors (PPARs) were examined. We show that PFDA alone produces pleiotropic effects on LI cells and that RX enhances some of these effects. Peroxisomal number and relative volume, as well as palmitoyl-CoA oxidase activity and protein, are increased by PFDA treatment, with a synergistic effect by RX. The latter, alone or in association with PFDA, induces catalase activity and protein, increases apoptosis and decreases cell proliferation. PPAR isotypes alpha and gamma were detected in LI cells. While the former is apparently unaffected by either treatment, the latter increases in response to PFDA, independent of the presence of RX. The results of this study are discussed in terms of PPARalpha activation and PPARgamma induction by PFDA, by either a direct or an indirect mechanism.

Topics: Acyl-CoA Oxidase; Alitretinoin; Apoptosis; Brain Neoplasms; Catalase; Cell Division; Decanoic Acids; Flow Cytometry; Fluorocarbons; Glioblastoma; Humans; Immunoblotting; Microscopy, Phase-Contrast; Oxidoreductases; Peroxisome Proliferators; Peroxisomes; Receptors, Cytoplasmic and Nuclear; Transcription Factors; Tretinoin; Tumor Cells, Cultured