Table 3.
| Study | No of patients | Median OS for placebo, mo | Reasons why cited placebo group would be expected to have shorter OS compared with the IMPACT placebo group | Study funding source(s) |
| Zoledronic acid (16) | 208 | 15.5 | The study did not restrict enrollment to minimal or absent symptomatology. Among patients, 73% had baseline pain vs 47% in IMPACT. The study conducted before TAX 327 demonstrated a 2.9-month survival benefit for docetaxel, leading to its approval by the FDA in the year 2004 | Novartis Pharmaceuticals Corporation (now Novartis International AG) |
| Docetaxel (TAX 327) (10,17) | 335 | 19.2 | The study did not restrict enrollment to minimal or absent symptomatology, and 45% of patients had clinically significant baseline pain vs 0% in IMPACT. Baseline visceral metastases was present in 22% of patients vs 0% in IMPACT. Clinically significantly worse baseline performance status and Gleason scores than IMPACT patients | Aventis (now Sanofi S.A.) |
| Atrasentan (19) | 401 | 20.3 | The study excluded patients requiring opiate analgesia but, unlike IMPACT, did not enroll 40% of patients under explicit exclusion of all pain and with favorable Gleason scores. No eligibility restrictions on patients with visceral metastases were given. Enrolled from June 2001 to September 2002, before TAX 327 demonstrated a 2.9-month survival benefit for docetaxel, leading to its approval by the FDA. The study was conducted at 180 sites in 21 countries, with variable local supportive care practices, which could induce bias in either direction | Abbott Laboratories |
| ZD4054 phase II (20) | 107 | 17.3 | The study excluded patients requiring opiate analgesia, but unlike IMPACT, did not impose eligibility restrictions on ECOG status, visceral metastases, pain, and Gleason score. The study was conducted at 65 centers (of which only 12 were in North America) across four continents where placebo patients were given “best supportive care according to local practice,” which could induce bias in either direction | Astrazeneca PLC |
| Mitoxantrone (21) | Kantoff et al. (1) chose the arm receiving the low-dose prednisone (median OS = 19 months) for comparison, yet the mitoxantrone plus low-dose prednisone (median OS = 23 months) would represent a more appropriate comparator for the IMPACT placebo group in which 50.3% of patients received docetaxel and 8% received other chemotherapy. The IMPACT placebo group excluded patients with visceral metastases [6% of mitoxantrone group in the study by Berry et al. (21)] and enrolled 75.4% of patients with favorable Gleason scores. Patients were enrolled from March 1997 to Jan 1999, and the results were reported in the year 2001, before docetaxel was granted FDA approval | Immunex Corporation (now Amgen Inc) | ||
| Mitoxantrone plus prednisone arm | 56 | 23 | ||
| Prednisone alone arm | 63 | 19 | ||
| PROSTVAC phase II (9) | 40 | 16.6 | Post-treatment chemotherapy usage was neither prescribed nor monitored. Results reported for the 40 placebo patients are problematic for the many reasons outlined by Small and Fong (22) | BN Immunotherapeutics (now Bavarian Nordic) |
| GVAX (18) | ∼310† | 21.7 | Exclusion of opiate pain medication was the only enrollment criterion used to select for a favorable prognosis | Cell Genesys (now BioSante Pharmaceuticals Inc) |
*
FDA = US Food and Drug Administration; OS = overall survival.
†
There is an approximate number of participants given for this trial because full results have not been published. The study completed accrual of 626 patients in the year 2007, randomized 1:1 between study arms, and all patients completed the initial 6-month treatment period.