What are the significant adverse reactions to docetaxel (Taxotere) (75 mg/m² intravenous every three weeks) with prednisone in men with metastatic castration‑resistant prostate cancer, and what prophylactic measures and dose‑modification strategies are recommended?

Docetaxel Adverse Reactions in Prostate Cancer Patients

For men with metastatic castration-resistant prostate cancer receiving docetaxel 75 mg/m² every 3 weeks with prednisone, expect neutropenia as the most significant hematologic toxicity (grade 3-4 in approximately 53%), though febrile neutropenia occurs in only 14% of patients, with infection rates around 24%. 1

Major Adverse Reactions

Hematologic Toxicities

• Neutropenia is the predominant hematologic adverse event, with grade 3-4 neutropenia occurring in approximately 53% of patients on the standard 3-weekly regimen 1
• Febrile neutropenia develops in 14% of patients receiving docetaxel every 3 weeks 1
• Neutropenic infections occur in approximately 24% of patients 2
• Leucopenia (grade 3-4) affects approximately 29% of patients 2

Non-Hematologic Toxicities

• Cutaneous reactions: Severe or cumulative skin reactions can occur and may warrant dose reduction 3
• Alopecia: Hair loss is common with docetaxel therapy 4
• Gastrointestinal effects: Nausea, vomiting, and diarrhea are frequently reported 4
• Nail disorders: Nail changes are a characteristic side effect 4
• Peripheral neuropathy: Neurologic toxicity occurs in a subset of patients 4
• Fatigue: Reported in approximately 16% of patients (grade 3-4) 5

Overall Toxicity Profile

• Severe adverse effects (grade 3 or higher) occur in approximately 25% of patients receiving docetaxel plus prednisone 4
• Grade 3-5 adverse events were documented in 52% of patients receiving ADT plus docetaxel in the STAMPEDE trial 6

Prophylactic Measures

Mandatory Premedication

All patients must receive corticosteroid premedication to reduce fluid retention and hypersensitivity reactions. 3

• For metastatic castration-resistant prostate cancer: Given concurrent prednisone use, administer oral dexamethasone 8 mg at 12 hours, 3 hours, and 1 hour before docetaxel infusion 3
• Standard premedication regimen (other indications): Dexamethasone 16 mg per day (8 mg twice daily) for 3 days starting 1 day prior to docetaxel administration 3

Supportive Care Considerations

• Prophylactic G-CSF may be used to mitigate hematological toxicities, particularly in high-risk patients 3
• Patients should be treated in facilities equipped to manage potential complications including anaphylaxis 3

Dose Modification Strategies

Indications for Dose Reduction

Reduce docetaxel dose from 75 mg/m² to 60 mg/m² if any of the following occur: 3

• Febrile neutropenia develops
• Neutrophil count <500 cells/mm³ for more than 1 week
• Severe or cumulative cutaneous reactions
• Grade 3-4 peripheral neuropathy (hold treatment until resolution to grade ≤2, then resume at reduced dose)

Alternative Dosing Schedules

A 2-weekly regimen (50 mg/m² every 2 weeks) offers improved tolerability with similar or superior efficacy compared to the standard 3-weekly schedule. 1, 2

• The every-2-week regimen demonstrated median survival of 19.5 months versus 17.0 months with every-3-week dosing (p=0.015) 1
• Febrile neutropenia rate: 4% with 2-weekly versus 14% with 3-weekly administration 1
• Grade 3-4 neutropenia: 36% with 2-weekly versus 53% with 3-weekly regimen 2
• Neutropenic infections: 6% with 2-weekly versus 24% with 3-weekly dosing (p=0.002) 2
• Time to treatment failure was significantly longer with 2-weekly administration (5.6 vs 4.9 months; HR 1.3, p=0.014) 2

Clinical Application

• The 2-weekly or weekly docetaxel regimen may be particularly appropriate for very elderly or frail patients to improve tolerability 7
• Overall quality of life was similar between dosing schedules 1

Common Pitfalls to Avoid

• Do not use docetaxel 100 mg/m² in previously treated patients: This dose was associated with increased hematologic toxicity, infection, and treatment-related mortality 3
• Ensure adequate premedication: Failure to premedicate appropriately increases risk of severe hypersensitivity reactions and fluid retention 3
• Monitor for cumulative toxicity: Nail disorders, neuropathy, and cutaneous reactions can worsen with repeated cycles 4
• Consider dose reduction proactively in patients with baseline risk factors for neutropenia rather than waiting for severe complications 3