LOS ANGELES -- Results of a large-scale clinical trial, reported today by a UC San Francisco researcher, suggest that a compound called suramin offers substantial pain reduction and moderate delay in progression of prostate cancer for some patients who have become resistant to standard hormone treatment. The finding was presented by UCSF oncologist Eric Small, MD, the lead author of the study and the principal investigator of the UCSF portion of the multi-institutional trial, at the American Society of Clinical Oncology (ASCO) in Los Angeles. The finding, said Small, offers a new direction for substantial pain relief for patients with advanced prostate cancer.
The phase III clinical trial, designed to test the drug's efficacy, involved 458 patients, with an average age of 68, at 76 medical centers in the United States and Canada.
In the study, the researchers reported that a significantly greater number of patients receiving suramin, in combination with another anti-prostate tumor agent, hydrocortisone, experienced significant pain reduction, for a longer period of time, than patients receiving only hydrocortisone and a placebo. In addition, patients who did not receive suramin were 50 percent more likely to undergo further progression of the disease.
Suramin has long been suspected of being an anti-prostate cancer agent, but because it has always been administered in conjunction with hydrocortisone, itself a drug with modest anti-prostate cancer activity, its unique contribution has been unclear.
In the clinical trial, researchers determined that 43 percent of patients receiving suramin with hydrocortisone experienced a reduction in pain, in contrast to 28 percent of those with hydrocortisone and a placebo. Moreover, the duration of that pain reduction lasted an average of 240 days, in contrast to 69 days in those receiving just hydrocortisone and a placebo.
"We observed a persistent and statistically significant advantage in patients receiving suramin plus hydrocortisone with regards to pain, narcotic use or the combination of these parameters both at week six and the end of the 12 weeks of treatment," said Small, UCSF associate clinical professor of medicine and urology and co-director of the Urologic Oncology Program at UCSF/Mount Zion Cancer Center.
UCSF/Mount Zion is part of UCSF Stanford Health Care.
The researchers also determined that the suramin combination was more likely to slow the progression of the disease than the placebo combination. At any point during the 12 weeks of therapy, the placebo group had a higher likelihood of progression of the disease, as measured by bone scan, CAT scan or an increase in pain. At week six, for instance, progression rates for suramin were 16 percent, compared to 31 percent for placebo, and at week 12, the end of treatment, progression rates were 52 percent for suramin and 73 percent for placebo. "The majority of patients were deemed to have developed progressive disease during the study," said Small, "but the likelihood of developing progressive disease was always less in the suramin plus hydrocortisone group."
The clinical trial was "double-blind," meaning neither physicians nor patients knew who was receiving which drug combination, and patients were assigned one of the two treatments randomly.
All patients had metastatic prostate cancer, and were no longer responsive to conventional hormone therapy. All patients were receiving narcotic analgesics to treat the significant bone pain resulting from the spread of the cancer to the bones. Patients who had received radiation within 28 days or had previously had chemotherapy, were excluded from the study.
The most common adverse effects in both groups of patients were rash, weakness, fluid retention, nausea and vomiting, though patients receiving suramin had a higher likelihood of these side effects. Significant neurologic, kidney or liver toxicities were rare in both groups.
The mechanism of suramin's action is complex, said Small, and still has not been fully delineated.
Prostate cancer, the most common cancer in men, accounted for more than 40,000 deaths in the United States in 1997. Approximately 300,000 American men are diagnosed with the disease each year, one-quarter with metastatic cancer, which is cancer that has spread to other organs. Of the three quarters diagnosed with less advanced cancer, one-half will ultimately develop metastasized disease, according to Small.
Patients with advanced prostate cancer are treated with hormone therapy, and virtually all deaths result when patients become resistant to this treatment. Few therapeutic options exist, either for treating the disease or for controlling the pain.
The study was sponsored by the National Cancer Institute and Parke-Davis Pharmaceutical Research Corp.