Scientists from the M.D. Anderson Cancer Center, in Houston, said PG-TXL (polyglutamic acid paclitaxel) dramatically increases the sensitivity of tumor cells to the killing effects of radiation in preclinical studies.
PG-TXL, a water-soluble form of the cancer drug Taxol (paclitaxel), is being investigated for its use in combination with radiation therapy to expand its potential application to a broader population of cancer patients. It was developed at the M.D. Anderson Center, in Houston, and licensed to the Seattle-based Cell Therapeutics Inc. (See BioWorld Today, July 20, 1998, p. 1.)
In the study, paclitaxel was inked to a biodegradable polymer called polyglutamate, rendering the paclitaxel inactive and less toxic to animals than Taxol, even when delivered at 400 percent higher doses than the maximally tolerated dose of Taxol, researchers said.
The polymer becomes trapped in abnormal blood vessels of tumor tissue and is digested by tumor cells slowly, thus releasing paclitaxel directly into the tumor.
Findings were presented at the 90th annual meeting of the American Association for Cancer Research (AACR), in Philadelphia. In other news from the AACR meeting:
¿ Aeterna Laboratories Inc., of Quebec City, presented results that confirmed the anti-MMP activity in AE-941, further identified the mechanisms of action of AE-941, and validated the practice of using AE-941/Neovastat to treat non-small-cell lung cancer patients. AE-941 is an angiogenesis inhibitor being investigated for three therapeutic areas: oncology, dermatology and ophthalmology. It is entering a Phase III trial for the treatment of lung cancer.
¿ Alfacell Corp., of Bloomfield, N.J., presented the results of in vivo studies of the combination regimen of Onconase and doxorubicin, showing it had a significantly greater effect than either drug alone in fighting human MDA-MD-231 breast cancer. The combination had a significantly greater effect on prolonging survival, with a median survival time of 58 days for the control group, 72 days for Onconase, 76 days for doxorubicin and 187 days for the combination therapy. Onconase is in Phase III trials in patients with unresectable malignant mesothelioma.
¿ Cell Genesys Inc., of Foster City, Calif., noted that additional clinical data on its Phase I/II trial of GVAX prostate cancer vaccine were consistent with previous reported interim results that indicated the vaccine was safe and well tolerated, and resulted in anti-tumor activity as measured by blood levels of prostate-specific antigen. Of the 21 patients studied, 15 (71 percent) had disease stabilization and a decrease in the rate of rise of PSA levels.
¿ Demegen Inc., of Pittsburgh, said that its D2A21 peptide inhibited tumor growth by as much as 60 percent as compared to untreated animals. The compound destroys a cancer cell by attaching to its surface and disrupting its outer membrane. A preclinical study done by the University of Pittsburgh Cancer Institute showed D2A21 was effective using several routes of administration and did not cause any significant toxicities. D2A21 was used in preclinical studies to treat established aggressive prostate cancer in rats.
¿ ImClone Systems Inc., of New York, reported findings from two preclinical studies of C225, its lead cancer therapeutic, that showed anti-tumor activity in animal models of human pancreatic carcinoma. C225, a monoclonal antibody, is an inhibitor of the epidermal growth factor receptor, which is associated with cancer cell growth in a number of solid tumors. C225, when used with the anticancer drug gemcitabine, caused a 90 percent reduction in pancreatic tumors, compared with a 27 percent response rate using gemcitabine alone. C225, when used alone, resulted in significant tumor regression and destruction of liver metastases, when compared to treatment with gemcitabine.
¿ Ligand Pharmaceuticals Inc., of San Diego, reported that Targretin (bexarotene), when added to tamoxifen therapy, caused a complete or partial regression in 94 percent of tamoxifen-resistant primary breast tumors. As a result of the final analysis of these preclinical results, Ligand launched a Phase II trial in November to assess the effectiveness of Targretin capsules in the treatment of women with advanced breast cancer.
¿ Sugen Inc., of South San Francisco, Calif., reported that it dosed its first patient with an oral formulation of SU6668, a broad-spectrum tyrosine kinase inhibitor that combines both anti-angiogenic and anti-tumor properties. Preliminary data indicate that SU6668 has good oral bioavailability in humans, with measurable plasma levels observable for 24 hours. The Phase I study¿s oral dosing is taking place in patients who have failed all other treatment options.