Chemotherapy with Docetaxel is usually given on a once every three (3) week schedule of 75 mg/m2 administered intravenously + prednisolone (10 mg/day p.o.) for men with advanced prostate cancer. In the cases when the side effects are too difficult for a man to tolerate, the dose is often reduced to 50 mg/m2 administered intravenously + prednisolone (10 mg/day p.o.) every two (2) weeks.
It has always been assumed that the every two-week dosing is not as effective as the every three-week schedule with higher doses. Recently, a study done in Finland has suggested that men with advanced prostate cancer who are castrate resistant may have superior outcomes with less side effects at the lower, every two-week schedule.
The paper describing this study was published in Lancet Oncology. The study was a multi-centered clinical trial specifically designed to evaluate the efficacy of the two different treatment protocols.
The trial was conducted between March 31, 2004 and May 31, 2009. All men who were participating were castrate resistant and had a PSA score greater than 10.0. They were all chemotherapy naive.
The men were split into two groups, each group receiving either the two or three week protocol.
The study endpoint was time to treatment failure (TTTF).
One hundred eighty four (184) men were randomly assigned to the every three-week protocol and 176 men were assigned to the two-week protocol.
The study found that the median TTTF for the standard every three-week protocol was 4.9 months (range, 4.5 to 5.4 months). Grade 3 or 4 neutropenia was observed in 93/176 patients (53 percent). Grade 3 or 4 leukopenia was observed in 51/176 of the men (29 percent). Grade 3 or 4 febrile neutropenia was observed in 25/176 men (14 percent). Additionally, neutropenic infections of any grade were observed in 43/176 patients (24 percent).
For the men in the two-week protocol the median TTTF was 5.6 months (range, 5.0 to 6.2 months). Grade 3 or 4 neutropenia was observed in 61/170 men (36 percent). Grade 3 or 4 leukopenia was observed in 22/170 men (13 percent). Grade 3 or 4 febrile neutropenia was observed in 6/170 men (4 percent). Additionally, neutropenic infections of any grade were observed in 11/170 of the men (6 percent).
The authors conclude that, “Administration of docetaxel every 2 weeks seems to be well tolerated in patients with [mCRPC] and could be a useful option when 3-weekly single-dose administration is unlikely to be tolerated.”
It is my opinion that given the longer time to TTTF and the significantly better side effect profile, the lower dosage, every-two week schedule seems superior. This trial is limited by the small size, a larger trial and one that also evaluates survival seems needed at this time.
Joel T. Nowak, M.A., M.S.W.