Intermittent Chemo Feasible in AI Prostate Cancer Patients

August 1, 2006

The first large clinical trial to prospectively evaluate intermittent chemotherapy for androgen-independent prostate cancer showed that a minority of patients can be given chemotherapy "holidays" of clinically meaningful duration.

ATLANTA—The first large clinical trial to prospectively evaluate intermittent chemotherapy for androgen-independent prostate cancer showed that a minority of patients can be given chemotherapy "holidays" of clinically meaningful duration.

The finding comes from an initial analysis of the Androgen Independent Prostate Cancer Study of Calcitriol Enhancing Taxotere (ASCENT) trial, a multicenter randomized trial in metastatic androgen-independent prostate cancer (AIPC) patients. ASCENT investigators previously reported that

patients randomized to docetaxel (Taxotere) plus the investigational agent DN-101, an oral formulation of calcitriol (high-dose vitamin D), had improved survival, compared with patients receiving docetaxel plus placebo.

Median survival times were 24.5 months vs 16.4 months, respectively, a 33% reduction.

The current study, presented at the American Society of Clinical Oncology 42nd Annual Meeting (abstract 4518), assessed outcomes with intermittent chemotherapy in a

subset of these patients.

While the current standard of care in AIPC is 10 cycles of docetaxel given every 3 weeks, the further management of patients after completing this chemotherapy regimen has been undefined, according to principal investigator Tomasz M. Beer, MD, of Oregon Health and Science University and the Portland VA Medical Center.

He explained, "If we treat with 10 cycles of docetaxel-based chemotherapy, we expect that one-third of patients will complete treatment without evidence of disease progression or significant toxicity. We have not defined what to recommend to those patients beyond initial chemotherapy. Clearly, indefinite chemotherapy is not very practical because of the continuous exposure to increasing cumulative toxicity. Limited reports have suggested that in subsets of patients, retreatment with the same chemotherapy after a chemotherapy holiday is feasible. We built this intermittent chemotherapy approach into the ASCENT trial."

Patients in the ASCENT study

(n = 250) could opt to suspend treatment if they had a confirmed 50% or greater reduction in serum PSA and a serum PSA of 4 ng/mL or less. During the treatment holiday, PSA was monitored every 4 weeks, and in patients with measurable disease, CT scans were performed every 8 weeks. Chemotherapy was resumed when PSA rose by 50% or more over preholiday nadir and was 2 ng/mL or higher, or if there was other evidence of disease progression. The study was not powered to compare treatment holiday outcomes between the two study arms (docetaxel plus calcitriol or placebo).

Overall, 20% of the docetaxel/calcitriol arm participated in the intermittent phase of the study, as did 16% of the docetaxel/placebo arm. Out of 56 eligible patients, 45 ultimately went on chemotherapy holiday; 7 are still on break, 38 completed the first holiday, and 10 completed a second holiday. Patients who entered this phase of the study did not differ by age or distribution of metastatic sites, but, Dr. Beer noted, "They clearly were a more favorable subset, as indicated by better performance status, less measurable disease, lower PSA, higher hemoglobin, and lower serum alkaline phosphatase."

Initial Results

The initial results of the intermittent study suggest that patients can have a "clinically meaningful" holiday, Dr. Beer reported. Median duration of the first chemotherapy holiday was 17 weeks (range, 4 weeks to 74+ weeks). For 42% of patients, the chemotherapy holiday lasted at least 20 weeks. When these patients were retreated, 56% responded again (50% or greater reduction in PSA from post-holiday baseline), and 21% achieved stable disease, he reported.

"Beyond the first chemotherapy holiday, there are not much data, but 13 patients had two or more holidays, and 10 completed the second holiday," Dr. Beer commented. Median duration of the second break was 12 weeks, with a range of 7 to 23 weeks.

Dr. Beer concluded, "This is the first report of intermittent chemotherapy in androgen-independent prostate cancer that was prospectively tested in a large multinational trial. It showed that chemotherapy breaks are clinically meaningful and can be offered to a minority of patients, about 18% in this study. Upon retreatment, most patients respond again. Additional study is needed to define the place of this approach in the management of prostate cancer."