LOS ANGELES--Combined therapy with suramin and hydrocortisone(Drug information on hydrocortisone) significantly improved palliation over placebo plus hydrocortisone in hormone-refractory prostate cancer. The palliative improvement emerged within 6 weeks, and the difference between the regimens increased to the end of therapy, Eric Small, MD, reported at the ASCO integrated symposium on prostate cancer.
Compared with hydrocortisone and placebo, suramin and hydrocortisone delayed disease progression, provided superior pain relief, and reduced the need for narcotic analgesia.
"The design of this study allows us to conclude that the benefits of suramin that we observed are not attributable to antiandrogen withdrawal, concurrent use of hydrocortisone, or a placebo effect," said Dr. Small, associate clinical professor of medicine and urology, University of California, San Francisco. "The data suggest that suramin/hydrocortisone, given on the current dosing schedule, is well tolerated and can be used in an outpatient, university, or community setting."
Several published reports have demonstrated suramins antitumor activity in prostate cancer, but the sum total of the literature includes conflicting findings on efficacy, Dr. Small said. In an effort to clarify the potential role of suramin in palliation of hormone-refractory prostate cancer, investigators in the United States and Canada randomized 458 patients to hydrocortisone plus placebo or to hydrocortisone plus suramin.
All of the patients had metastatic, hormone-refractory disease with evidence of progression. Other entry criteria included a requirement for scheduled narcotic analgesia for pain, anorchid testosterone levels, a PSA level greater than 10 ng/mL, and rising PSA despite withdrawal of antiandrogen therapy.
In both treatment groups, patients received 25 mg of hydrocortisone in the morning and 15 mg in the evening throughout the study. Suramin was dosed to maintain a concentration of 100 to 300 µg/mL. During the first week, patients received five daily, 1-hour infusions of suramin or placebo. The schedule was curtailed to two infusions during weeks 2 and 3, and then weekly infusions continued for a total of 12 weeks.
Patients who progressed on hydrocortisone and placebo could cross over to the suramin regimen. While allowing all patients to receive suramin, this crossover design makes comparison of survival for each treatment arm inappropriate, Dr. Small said.
Each night, patients used a visual analog scale to rate their pain over the past 24 hours, and recorded daily narcotic use. Bone scans and abdominal CT scans were obtained at baseline and after 12 weeks, and PSA levels were measured weekly.
Decreased Pain Scores
By week 6, patients on the suramin regimen had a 1.07 decrease in mean pain score, compared with a 0.61 decrease in the monotherapy group (P = .0230). At the end of therapy, the suramin-hydrocortisone combination was associated with a 1.01 mean decrease in pain score, compared with 0.28 for hydrocortisone and placebo (P = .0008).
A meaningful pain response was defined as a decrease in pain score of 3 or more or at least a 33% decrease in narcotic use. On that basis, 42% of the suramin patients had a pain response vs 28% of the hydrocortisone-placebo group (P = .001). The median duration of pain response was 240 days with suramin vs 90 days for hydrocortisone plus placebo(P = .0027).
Suramin also increased the percentage of patients who had PSA declines that exceeded 50%, though PSA response was modest in both groups, 32% vs 16% (P = .001). At a median follow-up of 21 months, the relative risk of disease progression was 1.52 for hydrocortisone and placebo, compared with hydrocortisone and suramin.
The two treatment groups had similar adverse-effect profiles, and the majority of adverse events were grades 1-2 in severity, Dr. Small said. The most common side effects in the suramin group were rash (57%), asthenia (54%), and nausea/vomiting (44%), and in the placebo group, asthenia (40%), nausea/vomiting (33%), and edema (30%).
Clear Clinical Benefit
Suramin produced a "clear clinical benefit" for selected patients, said discussant Howard Scher, MD, an oncologist at Memorial Sloan-Kettering Cancer Center. "We must keep in mind, however, that pain-related and antitumor effects are often dissociated. We must not abandon our efforts to identify new approaches that act directly against the tumor."
Noting that suramin did not improve survival in the trial, Dr. Scher argued that the regimen does not represent a new standard of care for hormone-refractory disease. "But we have identified an additional therapy that can provide palliation and delay progression in patients with symptomatic disease," he said.