CHICAGO—Tasquinimod, a novel biologic agent, may significantly slow the rate of disease progression and improve progression-free survival in patients with metastatic castrate-resistant prostate cancer (CRCP), according to a new study presented at the American Society of Clinical Oncology annual meeting.

“Tasquinimod may be considered a bridge between hormonal therapy and chemotherapy,” said the principal investigator, Roberto Pili, MD, Professor of Oncology at Roswell Park Cancer Institute in Buffalo, N.Y. “The most common side effects were nausea, fatigue, constipation, and decreased appetite. However, those occurred in less than 30% of the patients. The side effect profile looks acceptable and the side effects were all manageable and I think you can say that compared to chemotherapy the side effects were better.”

Tasquinimod is a quinoline-3-carboxamide derivative that has been shown to have anti-angiogenic properties and anti-tumor activity in prostate cancer models. Phase 1 studies in prostate cancer indicate that it is well tolerated and may delay prostate cancer progression. In a recently completed phase 2 study, researchers found that men with metastatic disease who received tasquinimod experienced a doubling in their progression-free survival time compared with men who received a placebo.

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The studies have been sponsored by the Swedish pharmaceutical company Active Biotech, which manufactures tasquinimod.

“The mechanism of action is still unclear, but it appears to be twofold,” Dr. Pili said. “The compound may work as an angiogenesis inhibitor, disrupting the formation of new blood vessels to the tumor, which the tumor needs to grow. In addition, it may act as an immunomodulator, enhancing the body’s immune response to the cancer.”

For the current study, he and his collaborators randomly assigned 206 men with a median age of 72.5 years (range 46-89 years) to receive either tasquinimod or placebo. All men had metastatic CRPC and, despite receiving hormone therapy, still experienced disease progression. None of the subjects had received chemotherapy and all were asymptomatic when enrolled. Men in the treatment group received a daily oral dose of tasquinimod, beginning with an initial dose level of 0.25 mg/day and escalating to 1.0 mg/day over four weeks.

After six months, 57% of the men receiving tasquinimod showed no disease progression compared with 33% of placebo recipients. The time that tasquinimod-treated men remained progression-free was nearly double that of the placebo group (24.7 vs. 12.9 weeks). Patients had the same response to treatment regardless of where the cancer had metastasized.

Disease progression was determined using bone and computed tomography scans and by ascertaining whether patients had any symptoms such as pain or fatigue. They did not rely on PSA levels.

“Interestingly, we did not see an effect on PSA levels,” Dr. Pili told Renal & Urology News.  “This is one of the first studies to show that PSA may be deceiving. We might not see a change in PSA level but there is a clinical benefit.”