Cell Therapeutics, Inc. (CTI) announced encouraging interim results of a phase II clinical study of Opaxio (paclitaxel poliglumex, PPX) combined with temozolomide (TMZ) and Radiotherapy (RT) in patients with newly diagnosed high-grade malignant brain tumours (astrocytomas and glioblastomas). While not a randomized trial, treatment with Opaxio, TMZ and RT resulted in a median Progression Free Survival (PFS) of 13.5 months. Median Overall Survival (OS) has not yet been reached with a median follow-up of 22 months. The study was presented by Drs Suriya Jeyapalan, Heinrich Elinzano and Mark Goldman, Assistant Professors of Neurology and Neurosurgery, Brown University Oncology Group at the 2011 American Society of Clinical Oncology Annual Meeting.

Opaxio is a potent radiosensitizer that increased the curability rate of cancers in preclinical models without increasing toxicity to normal tissues (Int. J. Rad. Oncol. Biol. Phys., 55:707-712, 2003). The present study was performed to determine the safety and efficacy of Opaxio when it was added to standard therapy with radiation and temozolomide for unresectable high grade brain tumours (Anaplastic Astrocytomas (AA) and
Glioblastoma Multiforme (GBM)).

“The data from the Opaxio study is provocative. With an overall survival not yet reached at a median follow-up of 22 months, the addition of Opaxio to the treatment of GBM could represent a major advance in prolonging survival in this otherwise rapidly fatal disease,” commented Howard Safran, MD, Head of the Brown University Oncology Group. “We look forward to confirming these findings in a randomized controlled trial of Opaxio plus RT compared to TMZ plus RT in patients who are known to have limited benefit from TMZ due to expression of a gene termed MGMT that adversely impacts the effectiveness of alkylating agents such as TMZ.”

In the current study, 25 patients were enrolled with confirmed high-grade glioma, of which 17 patients (68%) had GBM and 8 patients (32%) had AA. Patients received Opaxio with TMZ and RT for six weeks. The main toxicity reported was grade 4 thrombocytopenia and neutropenia (6 patients (24%)). These toxicities were felt to be due to a potential drug interaction between Opaxio and TMZ and/or and other concomitant medications. Among the 22 evaluable patients, the overall response rate was 45% (ten of 22) with 27% (six of 22) of patients achieving a complete response. With a median follow-up of 22 months, 76% of patients remained free from disease progression at 6 months with an overall median PFS of 14.9 months (13.5 months for patients with GBM).

Opaxio (paclitaxel poliglumex, CT-2103), which was formerly known as Xyotax, is an investigational, biologically enhanced, chemotherapeutic that links paclitaxel, the active ingredient in Taxol, to a biodegradable polyglutamate polymer, which results in a new chemical entity. When bound to the polymer, the chemotherapy is rendered inactive, potentially sparing normal tissue's exposure to high levels of unbound, active chemotherapy and its associated toxicities.

Blood vessels in tumour tissue, unlike blood vessels in normal tissue, are porous to molecules like polyglutamate. Based on preclinical studies, it appears that Opaxio is preferentially distributed to tumours due to their leaky blood vessels and trapped in the tumour bed allowing significantly more of the dose of chemotherapy to localize in the tumour than with standard paclitaxel. Once inside the tumour cell, enzymes metabolize the protein polymer, releasing the paclitaxel chemotherapy.

CTI is a biopharmaceutical company committed to developing an integrated portfolio of oncology products aimed at making cancer more treatable.