Phase II trial of tesmilifene plus mitoxantrone and prednisone for hormone refractory prostate cancer: high subjective and objective response in patients with symptomatic metastases.

Abstract

PURPOSE:

Symptomatic, hormone refractory prostate cancer (HRCAP) is a major cause of morbidity with a median survival of less than 12 months and a 2-year survival of only up to 10% in most series. Mitoxantrone has been approved by the Food and Drug Administration for HRCAP. Preliminary data suggest that DPPE (N,N-diethyl-2-[4-(phenylmethyl) phenoxy]-ethanamine) or tesmilifene modulates cytotoxics to enhance the anticancer effect. In this phase II trial we assessed whether there is sufficient evidence of enhanced efficacy of DPPE and mitoxantrone to lead to a phase III clinical trial.

MATERIALS AND METHODS:

A total of 29 patients with a median age of 73 years, of whom 10% were older than 80 years, with progressive HRCAP received 5.3 mg/kg DPPE intravenously every 3 weeks, 12 mg/m mitoxantrone intravenously every weeks and 5 mg prednisone orally twice daily. All patients had pain at presentation, while 97% had bone metastases, 10% had liver metastases and 17% had lung metastases. Median prostate specific antigen (PSA) was 210 ng/ml (IQR 77 to 430).

RESULTS:

Of the patients 75% had some pain improvement, 66% had decreased analgesia, 59% had a PSA decrease of 50% or greater and 45% had a PSA decrease of 75% or greater. Actual (not actuarial) 2-year survival was 21%.

CONCLUSIONS:

Despite major limitations of historical comparison the PSA decrease and decreased symptoms with DPPE-mitoxantrone-prednisone compare favorably to those of mitoxantrone-prednisone and docetaxel-estramustine in the literature. The 2-year survival rate of 21% mandates further assessment. This will be tested in a phase III Southwest Oncology Group trial.

• Authors: D Raghavan, L J Brandes, K Klapp, T Snyder, E Styles, D Tsao-Wei, G Lieskovsky, D I Quinn, E W Ramsey
• Journal: The Journal of urology (J Urol) Vol. 174 Issue 5 Pg. 1808-13; discussion 1813 (Nov 2005) ISSN: 0022-5347 [Print] United States
• PMID: 16217292 (Publication Type: Clinical Trial, Clinical Trial, Phase II, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Phosphatidylethanolamines
• 1,2-dipalmitoyl-3-phosphatidylethanolamine
• Mitoxantrone
• Prostate-Specific Antigen
• Prednisone

Topics

• Adenocarcinoma (drug therapy, mortality, pathology, secondary)
• Aged
• Aged, 80 and over
• Antineoplastic Combined Chemotherapy Protocols (adverse effects, therapeutic use)
• Dose-Response Relationship, Drug
• Drug Administration Schedule
• Humans
• Male
• Maximum Tolerated Dose
• Middle Aged
• Mitoxantrone (administration & dosage)
• Neoplasm Staging
• Phosphatidylethanolamines (administration & dosage)
• Prednisone (administration & dosage)
• Prognosis
• Prostate-Specific Antigen (blood)
• Prostatic Neoplasms (diagnosis, drug therapy, mortality)
• Survival Analysis
• Treatment Outcome