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

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/m2 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/m2 daily during radiotherapy (60 Gy) and 150-200 mg/m2 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

Acute mountain sickness.

Acute mountain sickness (AMS) is a clinical syndrome occurring in otherwise healthy normal individuals who ascend rapidly to high altitude. Symptoms develop over a period ofa few hours or days. The usual symptoms include headache, anorexia, nausea, vomiting, lethargy, unsteadiness of gait, undue dyspnoea on moderate exertion and interrupted sleep. AMS is unrelated to physical fitness, sex or age except that young children over two years of age are unduly susceptible. One of the striking features ofAMS is the wide variation in individual susceptibility which is to some extent consistent. Some subjects never experience symptoms at any altitude while others have repeated attacks on ascending to quite modest altitudes. Rapid ascent to altitudes of 2500 to 3000m will produce symptoms in some subjects while after ascent over 23 days to 5000m most subjects will be affected, some to a marked degree. In general, the more rapid the ascent, the higher the altitude reached and the greater the physical exertion involved, the more severe AMS will be. Ifthe subjects stay at the altitude reached there is a tendency for acclimatization to occur and symptoms to remit over 1-7 days

Pegylated liposomal doxorubicin-efficacy in patients with recurrent high-grade glioma

Pegylated liposomal doxorubicin administered alone or in combination with tamoxifen is safe and moderately effective in patients with recurrent high-grade glioma. None of the putative predictors for response that were evaluated proved to be significant in this setting