Paclitaxel Poliglumex/Capecitabine regimen well tolerated and active in metastatic breast cancer

At the 2008 Annual Meeting of the American Society of Clinical Oncology (ASCO), data were presented from a phase II investigator-sponsored trial paclitaxel poliglumex (Opaxio, CT-2103) in combination with capecitabine in first-line treatment of patients with metastatic breast cancer (MBC).

The goals of the study were to explore the tolerability and objective anti-tumor response rate as well as the disease-free progression and survival times of the regimen. Although the study did not meet its pre-defined endpoint of 21 or more responses in the first 41 patients, 20 patients (42 percent) of the 48 evaluable patients demonstrated a confirmed tumor response, including two complete responses and 18 partial responses. The authors concluded the combination of paclitaxel poliglumex and capecitabine was well tolerated and active in MBC. Opaxio is being developed by Cell Therapeutics, Inc.

"Given the convenient dosing schedule, a 15 minute infusion every 3 weeks, as well as no requirement for premedications and minimal hair loss associated with Opaxio compared to other taxanes, the goal of the study was to determine if Opaxio combined with capecitabine, an oral chemotherapy agent, as first- line therapy in metastatic breast cancer would prove to be an active and relatively well tolerated regimen," said Jack W. Singer, M.D., Chief Medical Officer of CTI. "The severe toxicities included neutropenia without neutropenic fever, neuropathy, and cutaneous toxicity that is most likely from capecitabine. We agree with the authors conclusions that the combination of Opaxio and capecitabine had efficacy similar to other taxane/capecitabine combinations and was well tolerated and active in this patient population."

This study was conducted to examine the tolerability and efficacy of the combination of Opaxio and capecitabine in first-line patients with MBC. Between April 2006 and April 2007, 48 patients were treated. Median duration of response was estimated to be 9.9 months and 5.7 months, respectively. Estimated six-month overall survival was 86 percent and estimated progression- free survival was 45 percent. The most common severe (grade 3 or 4) side effects reported included leucopenia in nine patients, neutropenia in eight patients, neuro-sensory side effects in four patients, skin reaction-hand/foot in four patients, and dyspnea in three patients. Approximately half of the patients (25 of 47) experienced a grade 3 adverse event and 13 percent experienced a grade 4 adverse event.

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(R), 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 tumor 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 tumors due to their leaky blood vessels and trapped in the tumor bed allowing significantly more of the dose of chemotherapy to localize in the tumor than with standard paclitaxel. Once inside the tumor cell, enzymes metabolize the protein polymer, releasing the paclitaxel chemotherapy. Preclinical and clinical studies support that Opaxio metabolism by lung cancer cells may be influenced by estrogen, which could lead to enhanced release of paclitaxel and efficacy in women with lung cancer compared to standard therapies.

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