Paclitaxel Poliglumex, Temozolomide, and Radiation for Newly Diagnosed High-grade Glioma

Abstract

PPX could not be safely combined with temozolomide due to grade 4 hematologic toxicity. However, the favorable progression-free and overall survival suggest that PPX may enhance radiation for glioblastoma. A randomized study of single agent PPX/radiation versus temozolomide/radiation for glioblastoma without MGMT methylation is underway.

Longitudinal DSC-MRI for Distinguishing Tumor Recurrence From Pseudoprogression in Patients With a High-grade Glioma

“…Instead, they contained CD68-positive cells, suggesting a contribution from macrophages and/or activated microglia, and "quiescent" tumor cells with Ki-67 (cellular marker for proliferation) typically <5%. 18 Thus, the composition of PsP in our study appears to reside somewhere between necrosis and active tumor in a histopathologic spectrum, likely contributing to the overlapping rCBVs for PsP and PD at initial progressive enhancement. .…”

“…18 Institutional Review Boards of participating hospitals approved this HIPAA-compliant study. Patients received PPX (40 to 50 mg/m 2 ), TMZ (75 mg/m 2 /d), and concurrent radiotherapy (2 Gy/d, 5 d/wk, 60 Gy total dose) over 6 weeks, and adjuvant TMZ (150 to 200 mg/m 2 Â5 d every 28 d) until disease progression.…”

“…19 Preclinically, PPX demonstrated a tumor tissue radiation enhancement factor of >4.0 as compared with 1.5 to 2.0 for paclitaxel. 19 The regimen of PPX, TMZ, and radiation induced a high rate of PsP as assessed by posttreatment biopsy/surgical resection and interval follow-up, 18 and PPX-treated high-grade gliomas may…”

“…We previously reported a 25-patient phase II multi-institutional study of patients with high-grade glioma treated with the combination of paclitaxel poliglumex (PPX), TMZ, and concurrent radiation. 18 PPX is a drug conjugate that links paclitaxel to a biodegradable polymer, poly-L-glutamic acid. 19 Preclinically, PPX demonstrated a tumor tissue radiation enhancement factor of >4.0 as compared with 1.5 to 2.0 for paclitaxel.…”

The proteomic landscape of glioma stem-like cells

“…The commonly accepted treatment protocol for GBM involves surgical resection, followed by chemotherapy treatment (usually with TMZ as adjuvant chemotherapy), and radiation [6], but a recent study has demonstrated the effectiveness of combination therapies using TMZ and paclitaxel [64]. Another study, using paclitaxel poliglumex in combination with TMZ and concurrent radiation, showed some promise in terms of overall survival, but the drugs could not be combined safely due to toxicity issues [65]. Therefore, it would be useful to measure the effectiveness of SYMPK knockdown to enhance the effectiveness of a combined chemotherapeutic regimen in GSCs.…”