Employing the treatment-free interval of intermittent androgen ablation to screen candidate prostate cancer therapies.
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.
Mao
Shifeng
S
Department of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030-3721, USA.
Daliani
Danai D
DD
Wang
Xuemei
X
Thall
Peter F
PF
Do
Kim-Anh
KA
Perez
Cherie A
CA
Brown
Melissa A
MA
Bouchillon
Kathleen
K
Carter
Cindy M
CM
Logothetis
Christopher J
CJ
Kim
Jeri
J
D000230:Adenocarcinoma / Q000097:blood / Q000175:diagnosis / Q000628:therapy*; D000276:Adjuvants, Immunologic / Q000008:administration & dosage / Q000627:therapeutic use*; D000281:Administration, Intranasal; D000726:Androgen Antagonists / Q000627:therapeutic use*; D020533:Angiogenesis Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use*; D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use; D003131:Combined Modality Therapy; D004151:Dipeptides / Q000008:administration & dosage / Q000627:therapeutic use*; D018450:Disease Progression; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D006801:Humans; D008297:Male; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy; D011471:Prostatic Neoplasms / Q000097:blood / Q000175:diagnosis / Q000628:therapy*; D016896:Treatment Outcome
D000276:Adjuvants, Immunologic; D000726:Androgen Antagonists; D020533:Angiogenesis Inhibitors; D018931:Antineoplastic Agents, Hormonal; D004151:Dipeptides; C060736:thymogen