Chemotherapy for hormone-sensitive or hormone-resistant prostate cancer

A randomized trial showed improved pain control in patients with hormone-resistant prostate cancer treated with mitoxantrone plus prednisone compared with those treated with prednisone alone.[58] Differences in OS or measured global QOL between the two treatments were not statistically significant.

Docetaxel has been shown to improve OS compared with mitoxantrone. In a randomized trial involving patients with hormone-refractory prostate cancer, docetaxel (75 mg/m2 every 3 weeks) and docetaxel (30 mg/m2 weekly for 5 out of every 6 weeks) were compared with mitoxantrone (12 mg/m2 every 3 weeks). All patients received oral prednisone (5 mg bid). Patients in the docetaxel arms also received high-dose dexamethasone pretreatment for each docetaxel administration (8 mg given at 12 hours, 3 hours, and 1 hour before the 3-week regimen; 8 mg given at 1 hour before the 5 out-of-every-6 weeks' regimen).[59]

Docetaxel has been shown to improve OS compared with mitoxantrone. In a randomized trial involving patients with hormone-refractory prostate cancer, docetaxel (75 mg/m2 every 3 weeks) and docetaxel (30 mg/m2 weekly for 5 out of every 6 weeks) were compared with mitoxantrone (12 mg/m2 every 3 weeks). All patients received oral prednisone (5 mg bid). Patients in the docetaxel arms also received high-dose dexamethasone pretreatment for each docetaxel administration (8 mg given at 12 hours, 3 hours, and 1 hour before the 3-week regimen; 8 mg given at 1 hour before the 5 out-of-every-6 weeks' regimen).[59]

OS at 3 years was statistically significantly better in the 3-weekly docetaxel arm (18.6%) than in the mitoxantrone arm (13.5%, HRdeath, 0.79; 95% CI, 0.67–0.93).

Docetaxel has been shown to improve OS compared with mitoxantrone. In a randomized trial involving patients with hormone-refractory prostate cancer, docetaxel (75 mg/m2 every 3 weeks) and docetaxel (30 mg/m2 weekly for 5 out of every 6 weeks) were compared with mitoxantrone (12 mg/m2 every 3 weeks). All patients received oral prednisone (5 mg bid). Patients in the docetaxel arms also received high-dose dexamethasone pretreatment for each docetaxel administration (8 mg given at 12 hours, 3 hours, and 1 hour before the 3-week regimen; 8 mg given at 1 hour before the 5 out-of-every-6 weeks' regimen).[59]

However, the OS rate for the 5 out-of-every-6 weeks docetaxel regimen was 16.8%, which was not statistically significantly better than mitoxantrone.

Docetaxel has been shown to improve OS compared with mitoxantrone. In a randomized trial involving patients with hormone-refractory prostate cancer, docetaxel (75 mg/m2 every 3 weeks) and docetaxel (30 mg/m2 weekly for 5 out of every 6 weeks) were compared with mitoxantrone (12 mg/m2 every 3 weeks). All patients received oral prednisone (5 mg bid). Patients in the docetaxel arms also received high-dose dexamethasone pretreatment for each docetaxel administration (8 mg given at 12 hours, 3 hours, and 1 hour before the 3-week regimen; 8 mg given at 1 hour before the 5 out-of-every-6 weeks' regimen).[59]

QOL was also superior in the docetaxel arms compared with mitoxantrone (P = .009).[60][Levels of evidence A1 and A3]

In another randomized trial involving patients with hormone-refractory prostate cancer, a 3-week regimen of estramustine (280 mg PO tid for days 1 to 5, plus daily warfarin and 325 mg aspirin to prevent vascular thrombosis), and docetaxel (60 mg/m2 IV on day 2, preceded by dexamethasone [20 mg × 3 starting the night before]) was compared with mitoxantrone (12 mg/m2 IV every 3 weeks) plus prednisone (5 mg qd).[61][Level of evidence A1]

In another randomized trial involving patients with hormone-refractory prostate cancer, a 3-week regimen of estramustine (280 mg PO tid for days 1 to 5, plus daily warfarin and 325 mg aspirin to prevent vascular thrombosis), and docetaxel (60 mg/m2 IV on day 2, preceded by dexamethasone [20 mg × 3 starting the night before]) was compared with mitoxantrone (12 mg/m2 IV every 3 weeks) plus prednisone (5 mg qd).[61][Level of evidence A1]

After a median follow-up of 32 months, median OS was 17.5 months in the estramustine/docetaxel arm versus 15.6 months in the mitoxantrone arm (HRdeath, 0.80; 95% CI, 0.67–0.97; P = .02).

In another randomized trial involving patients with hormone-refractory prostate cancer, a 3-week regimen of estramustine (280 mg PO tid for days 1 to 5, plus daily warfarin and 325 mg aspirin to prevent vascular thrombosis), and docetaxel (60 mg/m2 IV on day 2, preceded by dexamethasone [20 mg × 3 starting the night before]) was compared with mitoxantrone (12 mg/m2 IV every 3 weeks) plus prednisone (5 mg qd).[61][Level of evidence A1]

Global QOL and pain palliation measures were similar in the two treatment arms.[62][Level of evidence A3]

A 2-weekly regimen of docetaxel has been compared with a 3-weekly regimen. OS appeared to be better in the 2-week regimen, and hematologic toxicity was less.[63][Level of evidence A1]

A 2-weekly regimen of docetaxel has been compared with a 3-weekly regimen. OS appeared to be better in the 2-week regimen, and hematologic toxicity was less.[63][Level of evidence A1]

In the trial, 361 men with metastatic hormone-resistant prostate cancer were randomly assigned to receive docetaxel either in a 2-weekly regimen (50 mg/m2 IV) or a 3-weekly regimen (75 mg/m2 IV) until progression. All patients were also to receive prednisolone (10 mg PO qd) and dexamethasone (7.5–8.0 mg qd), starting the day before and continuing for 1 to 2 days after each docetaxel dose. Fifteen randomly assigned patients (4.2%) were deemed ineligible in retrospect or withdrew consent, and they were dropped from the analysis.

A 2-weekly regimen of docetaxel has been compared with a 3-weekly regimen. OS appeared to be better in the 2-week regimen, and hematologic toxicity was less.[63][Level of evidence A1]

With a median follow-up of 18 months, there was a small difference in time to treatment failure, the primary end point of the study (5.6 months [95% CI, 5.0–6.2] vs. 4.9 months [95% CI, 4.5–5.4]; P = .014). However, there was a larger difference in median OS, a secondary end point, in favor of the 2-week regimen (19.5 months [95% CI, 15.9–23.1] vs. 17.0 months [95% CI, 15.0 –19.1]; P = .02).

A 2-weekly regimen of docetaxel has been compared with a 3-weekly regimen. OS appeared to be better in the 2-week regimen, and hematologic toxicity was less.[63][Level of evidence A1]

There was a lower rate of grade 3 to 4 neutropenia with the 2-week regimen (36% vs. 53%; P < .0001) and a lower rate of febrile neutropenia (4% vs. 14%; P = .001).

In patients with mCRPC and no previous chemotherapy, cabazitaxel and docetaxel appeared to provide similar results with respect to OS.[64]

In patients with mCRPC and no previous chemotherapy, cabazitaxel and docetaxel appeared to provide similar results with respect to OS.[64]

In the FIRSTANA trial (NCT01308567), 1,168 men with mCRPC were randomly assigned in a 1:1:1 ratio to receive cabazitaxel 20 mg/m2, cabazitaxel 25 mg/m2, or docetaxel 75 mg/m2 IV every 3 weeks (plus prednisone 10 mg PO qd) until disease progression. Median OS was similar across all three study arms and not statistically significantly different (24.5 vs. 25.2 vs. 24.3 months, respectively), with virtually overlapping survival curves.[64][Level of evidence A1]

In patients with mCRPC and no previous chemotherapy, cabazitaxel and docetaxel appeared to provide similar results with respect to OS.[64]

However, toxicities varied across the study arms, with adverse event rates of 41.2%, 60.1%, and 46.0%, respectively, which required urgent treatment.

In patients with mCRPC whose disease progressed during or after treatment with docetaxel, cabazitaxel was shown to improve survival compared with mitoxantrone in a randomized trial (NCT00417079).[65] In this trial, 755 such men were treated with prednisone (10 mg PO qd) and randomly assigned to receive either cabazitaxel (25 mg/m2 IV) or mitoxantrone (12 mg/m2 IV) every 3 weeks.[65][Level of evidence A1]

In patients with mCRPC whose disease progressed during or after treatment with docetaxel, cabazitaxel was shown to improve survival compared with mitoxantrone in a randomized trial (NCT00417079).[65] In this trial, 755 such men were treated with prednisone (10 mg PO qd) and randomly assigned to receive either cabazitaxel (25 mg/m2 IV) or mitoxantrone (12 mg/m2 IV) every 3 weeks.[65][Level of evidence A1]

Median OS was 15.1 months in the cabazitaxel arm and 12.7 months in the mitoxantrone study arm (HRdeath, 0.70; 95% CI, 0.59–0.83; P < .0001).

A noninferiority-design randomized trial compared cabazitaxel (20 mg/m2 IV every 3 weeks) with cabazitaxel (25 mg/m2 IV every 3 weeks) in a similar population of 1,200 men with mCRPC who had received previous docetaxel. The lower dose of cabazitaxel fulfilled noninferiority criteria with respect to OS (HRdeath, 1.024; upper boundary of CI, 1.184), but with less toxicity.[66][Level of evidence A1]

Paclitaxel.

Estramustine/etoposide.

Estramustine/vinblastine.

Estramustine/paclitaxel.