VCU chemist pioneers new anti-cancer drug

By Mary Beth Alford

RICHMOND, Va. – Virginia Commonwealth University chemist has helped develop a new platinum-based drug that attacks cancer cells by interrupting the replication of the cell’s DNA. BBR3464, which may be available to patients by 2004, is likely to benefit individuals with ovarian cancer, the disease that develops in nearly 25,000 women in the United States each year.

Nicholas Farrell, Ph.D., VCU chemistry professor, presented his findings at the 2000 International Chemical Congress of Pacific Basin Societies last month in Honolulu, HI. The weeklong scientific meeting, held once every five years, is hosted by the American Chemical Society, in conjunction with its counterparts in Australia, Canada, Japan and New Zealand.

Platinum-based drugs have been successfully used to treat cancer since 1978. Cisplatin and carboplatin, both platinum-based, are front-line treatments for many cancers, particularly ovarian and testicular tumors. Their use dramatically changed the prognosis for testicular cancer, but ovarian cancer cells frequently become resistant to cisplatin, which is still used today.

The first new platinum-based cancer drug in nearly three decades, BBR3464 is expected to treat lung, pancreatic and skin cancers, which are rarely treatable by current chemotherapy.

After cisplatin became the first platinum drug anti-cancer in 1978, drug-development efforts concentrated on adapting its structure, leading to the clinical use of carboplatin, a decade later. No structurally new platinum drugs had emerged from the laboratory until BBR3464, which entered clinical trials in 1998.

The agent also represents a breakthrough in platinum chemistry. "This drug breaks the pattern of what we considered necessary for a platinum compound to have anti-tumor activity," said Farrell, who also holds an appointment at VCU’s Massey Cancer Center. "This is a genuinely new structure class that opens up the possibilities of finding other classes that also have different activities."

In BBR3464, a new form of platinum has been modified to contain three platinum atoms, which bind differently and more effectively to DNA. The new drug is significantly more potent than cisplatin and can be given in much lower doses, helping to minimize side effects.

BBR3464 emerged from joint research by Farrell and Novuspharma SpA, a pharmaceutical firm based in Italy, and is licensed to Roche, a research-oriented health-care group. The clinical trials are being conducted by Novuspharma.

Phase I clinical trials, used to determine safe doses and possible side effects, were conducted in Europe in 1998 and 1999. The trial involved 47 patients in late stages of cancer that resisted other treatments.

"Three objective responses and regressions of disease were seen, including one patient who had pancreatic cancer that had spread to the liver," Farrell said. "After treatment with BBR3464, the liver metastases disappeared."

Farrell also said that partial responses occurred in lung cancer and melanoma patients. These results have led to more specific Phase II trials, started in England and the United States last year. Currently, more than 200 patients are involved in three trials determining the drugs’ effectiveness in ovarian, lung and gastric cancers. A trial in pancreatic cancer will be completed within the next two years. VCU’s Massey Cancer Center is anticipated to participated in the trials.

"There is no available treatment for patients with advanced cancers," Farrell said. "I expect that if the second round of studies proves successful, the drug could rapidly be approved by the Food and Drug Administration."

Primary research funding came from the American Cancer Society, which has supported Farrell’s research since 1989, and the National Institutes of Health.