From the Guidelines
Triplet therapy for prostate cancer, which combines androgen deprivation therapy (ADT) with docetaxel and darolutamide, is associated with significant side effects, including alopecia, neutropenia, fatigue, and anemia, but these are generally manageable with proper monitoring and supportive care. The most recent and highest quality study, the ARASENS trial 1, demonstrated that the addition of darolutamide to ADT and docetaxel improved overall survival in patients with metastatic castration-sensitive prostate cancer, with a 32% reduction in the risk of death. The side effects of this triplet therapy were similar to those expected from docetaxel, with the exception of rash and hypertension, which were more frequent in the darolutamide group.
Management Strategies
To manage the side effects of triplet therapy, the following strategies can be employed:
- Regular monitoring of blood counts, liver function, and blood pressure
- Prophylactic G-CSF (such as filgrastim) for neutropenia prevention
- Dose modifications when necessary
- Supportive care with antiemetics, growth factors, and hydration
- Maintenance of bone health with calcium and vitamin D supplementation
- Consideration of bone-targeted agents like zoledronic acid or denosumab for patients at high risk for skeletal complications
Treatment Decisions
Treatment decisions should be individualized based on the patient's performance status, comorbidities, and disease characteristics, as emphasized by the NCCN Prostate Cancer Panel 1. The use of triplet therapy is encouraged for patients with high-volume de novo disease who are fit for chemotherapy. Overall, the benefits of triplet therapy in improving survival outcomes in metastatic hormone-sensitive prostate cancer justify its use, despite the potential for significant side effects.
From the Research
Side Effects of Triplet Therapy for Prostate Cancer
The side effects of triplet therapy for prostate cancer have been documented in several studies 2, 3, 4, 5. Some of the common side effects include:
- Febrile neutropenia
- Diarrhea with infection
- Polyneuropathy
- Mucositis
- Xerostomia
- Weight loss
- Fatigue
Management Strategies for Side Effects
Management strategies for the side effects of triplet therapy for prostate cancer include:
- Close monitoring of patients for signs of adverse events
- Dose adjustments or interruptions of chemotherapy or other medications as needed
- Use of supportive care measures such as prophylactic granulocyte-colony stimulating factor (G-CSF) and osteoprotective agents
- Management of specific side effects such as febrile neutropenia and diarrhea with infection
Factors Affecting Outcomes
Factors affecting outcomes in patients receiving triplet therapy for prostate cancer include:
- Volume or burden of disease
- Timing of metastases relative to the original diagnosis
- Patient factors determining the appropriateness of therapy
- Simultaneous versus nonsimultaneous onset of chemotherapy and androgen receptor pathway inhibitor (ARPI)
Clinical Evidence
Clinical evidence from several studies 6, 4, 5 supports the use of triplet therapy for metastatic hormone-sensitive prostate cancer, with improved overall survival and PSA response compared to doublet therapy. However, the evidence also highlights the importance of careful patient selection and management of side effects to optimize outcomes.