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In a recent critique on (mHSPC), Kartolo and colleagues raised the controversial question as to whether docetaxel is a necessary agent in the treatment of these patients.

The landmark CHAARTED and STAMPEDE trials helped solidify the presence of docetaxel as standard of care for patients with mHSPC with high-grade high-volume disease, in addition to androgen-deprivation therapy (ADT). What to do post-docetaxel treatment remained problematic, as many of these patients were at high risk for progression or development of castrate-resistant disease while on ADT alone. This predicament led to the foundation of studies such as ARASENS, which involved use of triplet therapy (darolutamide, docetaxel, and ADT followed by continuation of darolutamide) for patients with newly diagnosed mHSPC.

ARASENS showed a significant benefit in overall survival (OS) in patients on triplet therapy compared with ADT with six cycles of docetaxel. Most of these patients had high-volume disease. The continuation of an anti-androgen (darolutamide in ARASENS, abiraterone acetate in the PEACE-1 trial) led to an improvement in overall survival. The concept of a triplet therapy upfront followed by maintenance is similar to that seen in other metastatic cancers such as non-small cell lung cancer, leading to an OS survival benefit.

For men with mHSPC and lower-volume disease, ADT with anti-androgen such as abiraterone remains an appropriate and acceptable standard of care option. The question remains, for these patients is the addition of docetaxel really necessary? Could unnecessary toxicities from cytotoxic chemo be potentially avoided?

The answer in my opinion depends on the burden and bulk of disease. Traditionally high-volume disease is defined by greater than or equal to four bony metastases and presence of non-skeletal visceral metastases. Commonly these patients present with symptoms and a very high prostate-specific antigen level. For these patients, triplet therapy is optimal as it could provide maximal cytoreduction of tumor. Furthermore, triplet therapy helps address what to do following the six cycles of docetaxel, as patients can remain on the anti-androgen, similar to a form of "maintenance" therapy.

For patients with low-volume asymptomatic disease, however, ADT+anti-androgen should remain standard of care. The addition of docetaxel, therefore, should be reserved for patients who may need it the most.

Rajasree Pia Chowdry, MD, is Assistant Professor of Clinical Medicine, Section of Hematology/Oncology, at LSU Health Sciences Center, Louisiana Cancer Research Center, in New Orleans.

Read the article here and an interview about it here.