Prostate-cancer-specific oncolytic virus

Cell Genesys, Inc. has announced data from a Phase I/II clinical trial of CG7870 oncolytic virus therapy in patients with localized recurrent prostate cancer. CG7870 is a replication-selective oncolytic adenovirus that was administered directly into the prostate. This resulted in reductions in serum levels of prostate-specific antigen (PSA) in 75% (9 out of 12) of patients with increased PSA levels at baseline. In the nine responders, PSA levels decreased by 25–50%, and all patients remained progression-free 6 months later. The treatment was well tolerated and did not result in any serious treatment-related side effects. The trial involved 20 patients who had recurrent prostate cancer following radiation therapy, but had not yet received hormone treatment. Ten patients were treated with a single administration of one of three doses of the oncolytic virus therapy.

Cell Genesys expects to initiate a follow-up Phase II trial of intra-prostatic CG7870 in combination with external beam radiation in early-stage, high-risk prostate cancer patients in early 2003. In preclinical studies, CG7870 showed a high therapeutic index of approximately 10,000:1. This means that it could have far fewer side effects than traditional chemotherapy, which only kills about six cancer cells for every normal cell that it kills. These data were presented last December at the International Conference on Gene Therapy of Cancer in San Diego, California. WEB SITE http://www.cellgenesys.com/

Antisense for pancreatic cancer

A Phase II clinical trial of ISIS 2503 in combination with gemcitabine has shown promise in the treatment of metastatic pancreatic cancer. ISIS 2503 is an antisense inhibitor of HRAS — an oncogene that is mutated or overepxressed in many cancers. Almost 60% of patients who received ISIS 2503 plus gemcitabine survived for 6 months or longer, with a median survival time of 6.7 months. This compares favourably with patients treated with gemcitabine alone, 46% of whom survived for 6 months, with a median survival time of 5.6 months. The open-label trial enrolled 48 patients with locally advanced or metastatic pancreatic cancer who had not received previous chemotherapy. Each patient received ISIS 2503 by continuous intravenous infusion for 2 weeks of a 3-week cycle, in combination with typical doses of gemcitabine on days 1 and 8.

New approaches to treating pancreatic cancer are urgently needed, as it is the fourth leading cause of cancer death in men and women in the United States. In 2002, more than 30,000 people will be diagnosed with pancreatic cancer and up to 30,000 will die from the disease. For all stages combined, the 1-year survival rate is only 21%. Isis Pharmaceuticals, Inc. is currently preparing to test ISIS 2503 in Phase III trials for pancreatic cancer, and Phase II clinical trials of this drug are also underway for metastatic breast and non-small-cell lung cancer. The results of the Phase II study were reported last December at the 6th National Institutes of Health Therapeutic Oligonucleotide Interest Group Symposium in Bethesda, Maryland. WEB SITE http://www.isispharm.com/