Older men (over 75 years) may consider having docetaxel chemotherapy despite their age. However, there should be a consideration of changing the dosing and the schedule.
A retrospective case series looking at men with metastatic castrate resistant prostate cancer (mCRPC) aged ≥80 years and treated with docetaxel between July 2006 and June 2012 at three community hospitals in Melbourne, Australia found that these men had a significant response rate to docetaxel. The actual treatment efficacy in this patient population was difficult to determine due to the retrospective nature of this study and the absence of a control group. However, just over half of the men derived clinical benefit from treatment in terms of ≥50% PSA response or improvement in their report pain levels. The researchers also observed that men who had a PSA response of ≥50% had longer overall survival than those who did not.
However, as expected, a substantial number of these older men in the study had increased treatment-related complications.
Weighing the potential benefits from the use of chemotherapy in this population of men against the additionally increased toxicities of the treatment makes the management of older men with mCRPC challenging. Subgroup analyses of other clinical trials and retrospective studies confirm the finding that chemotherapy in older men provides similar benefits as younger men receive, although at the cost of potentially increased toxicity.
Therefore, one potential strategy for older men is to use a weekly dosing scheduling with a lower dose of the drug at each infusion. This type of dosing is perceived to be better tolerated compared to the standard three times a week regimen.
In another post hoc analysis of the men aged ≥75 years in the TAX327 study, there was no difference in the type or frequency of toxicities between the weekly and 3-weekly docetaxel arms, although there were significantly more dose reductions required in men receiving 3-weekly treatment.
By contrast, a retrospective multicenter French study of 175 men aged ≥75 years, including 57 (32.6%) men aged ≥ 80 years, showed significantly higher rates of febrile neutropenia among those who received standard 3-weekly docetaxel. Whereas, those who received weekly treatment experienced more Grade 3–4 fatigue and were more likely to stop chemotherapy because of toxicity (30% vs. 8%), possibly due to a higher proportion of older and poor performance status of the men in this group.
The many new agents approved for men with mCRPC have also been shown to improve survival. These newer agents include cabazitaxel (which is another form of chemotherapy), abiraterone, enzalutamide, sipuleucel-T, and radium-223. Although optimal treatment sequencing has not been established, these newer agents are an attractive alternative to chemotherapy in elderly patients due to the lower rates of myelosuppression and sepsis. In a post hoc subgroup analyses of the phase III studies of abiraterone and enzalutamide, both agents were well tolerated in men aged ≥75 years, although the older men treated with abiraterone experienced higher rates of cardiac arrhythmias and peripheral edema than those aged <75 years.
In conclusion, carefully selected fit older men with mCRPC appear to tolerate docetaxel and derive clinical benefits from treatment, however, optimal dosing remains unclear. The new hormonal agents such as abiraterone and enzalutamide are attractive alternatives for these men due to lower rates of toxicity
Joel T. Nowak, MA, MSW wrote this Post. Joel is the CEO/Executive Director of Cancer ABCs. He is a Cancer Thriver diagnosed with five primary cancers - Thyroid, Metastatic Prostate, Renal, Melanoma, and the rare cancer Appendiceal cancer.