Intermittent and continuous chemotherapy with docetaxel – a summary of findings

This review examined intermittent and continuous docetaxel (Taxotere) treatment for metastatic castration-resistant prostate cancer (mCRPC). Researchers concluded that intermittent docetaxel treatment can be a feasible treatment option in the management of mCRPC.

Chemotherapy with docetaxel is often the first-line treatment for prostate cancer that continues to spread despite standard hormone therapy (also called metastatic castration-resistant prostate cancer or mCRPC). Docetaxel is associated with number of side effects. These can include low levels of red or white blood cells, fatigue, edemas (swelling), and nausea. In order to reduce side effects, docetaxel treatment can be applied intermittently, with breaks between treatments. However, the relative benefits of intermittent versus continuous docetaxel are still being investigated.

The aim of this review was to summarize findings on intermittent and continuous docetaxel in the treatment of mCRPC. 10 separate trials were analyzed. 6 trials followed the outcomes of intermittent chemotherapy with docetaxel (IC). 4 trials compared IC to continuous chemotherapy with docetaxel (CC). The average number of men included in each trial was 73.

One early study confirmed the feasibility of IC by finding stable PSA (prostate specific antigen; a protein elevated in the blood in prostate cancer) levels during treatment breaks (average 20 weeks). Men receiving IC reported significant improvements in fatigue. Another study found a treatment response of at least 50% (based on PSA levels) in 76% of men during the first cycle of IC. This was maintained during the second cycle (treatment response of at least 50% in 80% of men) and steadily reduced thereafter. Treatment breaks lasted between 18 and 22 weeks. On average, about half of men were eligible for IC.

Only 9.1% of men undergoing IC in a separate trial had disease progression after the first treatment break (average 18 weeks). 45.5% of men responded with a reduction of PSA levels of at least 50% after the second treatment cycle. Similar treatment response rates were reported in three further studies. 46 to 53% of men had reduced PSA levels of at least 50% after the first cycle. After the second cycle, 25 to 33% of men showed the same response. Nausea and vomiting improved significantly, as did quality of life. Average overall survival (time from treatment until death from any cause) among men with mCRPC undergoing IC was 21 months in one trial studied.

A further study reported similar overall survival between IC (average 19 months) and CC (average 21 months). There was also no difference in disease progression between the two treatment groups. Significant improvements in fatigue and overall health were noted.

Of the 3 remaining trials comparing IC and CC, one trial reported significantly longer overall survival for IC. Another trial observed similar overall survival in the two groups, but time until disease progression was significantly longer for IC. 43.2% of men receiving IC and 15.9% of men receiving CC were progression-free at 9 months. Across the three trials, a 50% treatment response after the first cycle was achieved in 42 to 53% of men. This was generally maintained at the second cycle and steadily reduced thereafter in 2 of the 3 trials. Side effects were significantly reduced with IC. However, IC had no significant effect on quality of life.

Researchers reported that the effectiveness of intermittent docetaxel was comparable to that of continuous treatment, with some significant reductions in side effects during treatment breaks.

Most of the trials included in this review were not randomized. Further trials that randomly assign patients to either intermittent or continuous treatment are needed.