Adaptive Therapy For Androgen Independent Prostate Cancer: A Randomized Selection Trial Of Four Regimens

Main Category: Prostate / Prostate Cancer
Also Included In: Urology / Nephrology;  Men's health;  Clinical Trials / Drug Trials
Article Date: 16 Dec 2007 - 0:00 PDT

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UroToday.com- In the November 2007 issue of the Journal of the National Cancer Institute, Dr. Thall and colleagues report on changing chemotherapy regimens based upon patient response and provide statistical modeling to assess outcomes.

They initiated the trial in 1998, prior to the establishment of docetaxel chemotherapy as the first line standard. However, the rationale and analysis provide insights into the approach of sequential regimens. Four chemotherapy regimens were studied:

CVD: cyclophosphamide, vincristine, and dexamethasone

KA/VE: Ketoconazole plus doxorubicin alternating with vinblastine plus estramustine

TEC: weekly paclitaxel, estramustine, and carboplatin

TEE: paclitaxel, estramustine, and topside

Patients were stratified by disease burden as low and high risk volume to balance the initial randomization. Patients received an 8-week course of treatment with one of the four regimens and were then evaluated. To continue with the same treatment, patients had to demonstrate evidence of benefit (PSA decline of >40%, objective regression, cancer-related symptom improvement and no new lesions). The same criteria were used to evaluate outcomes after second-line therapy.

A total of 150 patients were enrolled between 1998 and 2003 and analyzed. Median time from androgen deprivation therapy was 35 months. A total of 330 courses of chemotherapy were administered and overall 155 courses (47%) were deemed successful. Two successful courses were observed in 35 patients (23%) by means of first line treatment and an additional 9 patients had overall success with second line treatment. PSA reduction was the most common measure of success. Median overall survival from registration was 22 months. Estimated overall survival rates at 2, 3, 4, and 5 years were 45%, 26%, 15%, and 10%, respectively. While grade 4 events were uncommon, there were 110 grade 3 events among 68 patients. The observed per course success rates with the regimens were 57% for TEC, 52% for KA/VA, 45% for TEE, and 28% for CVD. Starting with the regimen having the most overall success and following with second line therapy that has the least cross-resistance is the approach that should be applied, according to the authors. A detailed analysis of response rates and response quality is included in the study.

Thall PF, Logothetis C, Pagliaro LC, Wen S, Brown MA, Williams D, Millikan RE

J Natl Cancer Inst. 99(21):1613-1622, November 2007

doi:10.1093/jnci/djm189

Reported by UroToday.com Contributing Editor Christopher P. Evans, M.D

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