Patients who no longer respond to hormone therapy have another option. The chemotherapy drug docetaxel (Taxotere) taken with or without prednisone (a steroid) is the standard chemotherapy regimen for patients who no longer respond to hormone therapy.
Docetaxel works by preventing cancer cells from dividing and growing. Patients receive docetaxel, along with prednisone, through an injection.
Side effects of docetaxel are similar to most chemotherapy drugs and include nausea, hair loss, and bone marrow suppression (the decline or halt of blood cell formation). Patients may also experience neuropathy (nerve damage causing tingling, numbness, or pain in the fingers or toes) and fluid retention.
Docetaxel, when used with or without prednisone, was the first chemotherapy drug proven to help patients live longer with advanced prostate cancer. The average survival was improved by about 2.5 months when compared to mitoxantrone with or without prednisone.
Docetaxel has the best results when given every three weeks as compared to weekly dosing.
Two randomized phase 3 studies evaluated docetaxel-based regimens in symptomatic or rapidly progressive disease (TAX 327 and SWOG 9916).334,409,410 TAX 327 compared docetaxel (every 3 weeks or weekly) plus prednisone to mitoxantrone plus prednisone in 1006 men.409 Every- 3-week docetaxel resulted in higher median overall survival than mitoxantrone (18.9 vs. 16.5 months; P = .009). This survival benefit was maintained at extended follow-up.410 The SWOG 9916 study also showed improved survival with docetaxel when combined with estramustine compared to mitoxantrone plus prednisone.334 Docetaxel is FDA-approved for metastatic CRPC. The standard regimen is every 3 weeks. An alternative to every-3-week docetaxel is a biweekly regimen of 50 mg/m2. This regimen is based on a large randomized phase 2 trial of 346 men with metastatic CRPC randomized to either every-2-week docetaxel or every-3-week docetaxel, each with maintenance of ADT and prednisone.411 Men treated with the every-2-week regimen survived an average of 19.5 months compared to 17.0 months with the every-3- week regimen (P = .015). Time-to-progression and PSA decline rate favored every-2-week therapy. Tolerability was improved with every-2- week docetaxel; febrile neutropenia rate was 4% versus 14% and other toxicities and overall quality of life were similar.
Docetaxel is included as an upfront option for men with progressive androgen-stimulated prostate cancer and distant metastases based on results from 2 phase 3 trials (ECOG 3805/CHAARTED and STAMPEDE).412,413 CHAARTED randomized 790 men with metastatic, androgen-stimulated prostate cancer to docetaxel plus ADT or ADT
alone.413 The patients in the combination arm experienced a longer OS than those in the ADT arm (57.6 months vs. 44.0 months; HR, 0.61; 95% CI, 0.47–0.80; P<.001). Subgroup analysis showed that the survival benefit was more pronounced in the 65% of participants with high-volume disease (HR, 0.60; 95% CI, 0.45–0.81; P<.001). Men with low-volume disease in CHAARTED may have derived a survival benefit from the inclusion of docetaxel (HR, 0.60; 95% CI, 0.32–1.13; P=.11), although median OS was not reached for either arm, and the number of patients was low.
The STAMPEDE trial, a multi-arm, multistage phase 3 trial, included patients with both M0 and M1 androgen-stimulated prostate cancer.412 The results in the M1 population essentially confirmed the survival advantage of adding docetaxel to ADT seen in the CHAARTED trial. In STAMPEDE, extent of disease was not evaluated in the 1087 men with metastatic disease, but the median OS for all patients with M1 disease was 5.4 years in the ADT-plus-docetaxel arm versus 3.6 years in the ADT-only arm (a difference of 1.8 years between groups compared with a 1.1-year difference in CHAARTED). The results of the STAMPEDE trial seem to confirm the results of the CHAARTED trial.
The panel added the use of docetaxel in combination with ADT and EBRT in fit men with high- and very-high-risk localized disease in the 2016 version of these guidelines. This recommendation is supported by results of the GETUG 12 trial, which randomized 413 men with high- or very-high risk prostate cancer to IMRT and ADT or ADT, docetaxel, and estramustine.414 After median follow-up 8.8 years, 8-year relapse-free survival was 62% in the combination therapy arm and 50% in the ADT- only arm (adjusted HR, 0.71; 95% CI, 0.54-0.94; P = .017). Estramustine has been shown to increase side effects without enhancing efficiency when added to docetaxel and is not recommended.415