Employing the treatment-free interval of intermittent androgen ablation to screen candidate prostate cancer therapies.

Abstract

BACKGROUND:

Because neither continuous nor intermittent hormonal therapy is curative, we designed a clinical model to screen new drugs for additive or synergistic effects with hormonal therapy and used IM862, a naturally occurring dipeptide with antiangiogenic and immunomodulatory properties, to test it.

METHODS:

Patients with prostate cancer who had rising PSA levels after radical prostatectomy and/or radiation therapy were given combined androgen ablation for 3 months. After 2 months' treatment, patients were randomly assigned in a double-blind fashion to receive intranasal IM862 or placebo daily. Treatment continued for 6 months or until disease progression, which was defined by a rising serum PSA level, the appearance of new skeletal or extraskeletal metastatic disease, or new symptoms requiring intervention.

RESULTS:

Seventy-one patients were evaluable for response. Median time to PSA progression was not reached in either group. At 6 months, disease had progressed in 14 (41%) of the 34 patients receiving treatment and 18 (49%) of the 37 receiving placebo (P = 0.39). No significant toxicities emerged.

CONCLUSIONS:

The model was demonstrated to be an efficient platform for new drug screening; however, IM862, though well tolerated, failed to demonstrate superiority over placebo in prolonging time to PSA progression.

• Authors: Shifeng Mao, Danai D Daliani, Xuemei Wang, Peter F Thall, Kim-Anh Do, Cherie A Perez, Melissa A Brown, Kathleen Bouchillon, Cindy M Carter, Christopher J Logothetis, Jeri Kim
• Journal: The Prostate (Prostate) Vol. 67 Issue 15 Pg. 1677-85 (Nov 01 2007) ISSN: 0270-4137 [Print] United States
• PMID: 17879948 (Publication Type: Clinical Trial, Phase II, Journal Article, Randomized Controlled Trial, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Adjuvants, Immunologic
• Androgen Antagonists
• Angiogenesis Inhibitors
• Antineoplastic Agents, Hormonal
• Dipeptides
• thymogen

Topics

• Adenocarcinoma (blood, diagnosis, therapy)
• Adjuvants, Immunologic (administration & dosage, therapeutic use)
• Administration, Intranasal
• Androgen Antagonists (therapeutic use)
• Angiogenesis Inhibitors (administration & dosage, therapeutic use)
• Antineoplastic Agents, Hormonal (therapeutic use)
• Combined Modality Therapy
• Dipeptides (administration & dosage, therapeutic use)
• Disease Progression
• Double-Blind Method
• Drug Administration Schedule
• Humans
• Male
• Neoplasm Recurrence, Local (drug therapy)
• Prostatic Neoplasms (blood, diagnosis, therapy)
• Treatment Outcome