Background
Methods
Development of systematic review
Inclusion criteria
Exclusion criteria
Literature search strategy
Methods of review
Synthesis of the evidence
Results
Literature search results
Antimicrotubule-based chemotherapy
Docetaxel
Trial | N randomized/evaluable | Treatment arms (dose) and schedule | Duration |
---|---|---|---|
Tannock, 2004 [64] | 1006/1006 | docetaxel (75 mg/m2) iv q 3 wks prednisone (5 mg) po twice daily dexamethasone (8 mg) at 12, 3, and 1 hr(s) prior to infusion | 10 cycles |
docetaxel (30 mg/m2) iv q wk for 5 wks prednisone (5 mg) po twice daily dexamethasone (8 mg) at 1 hr prior to infusion | 5 cycles | ||
mitoxantrone (12 mg/m2) iv q 3 wks prednisone (5 mg) po twice daily | 10 cycles | ||
Petrylak, 2004 [63] | 770/666 | docetaxel (60 mg/m2)* iv q 3 wks EMP (280 mg) po thrice daily q 3 wks dexamethasone (20 mg) po thrice daily q 3 wks | 12 cycles |
mitoxantrone (12 mg/m2)* iv q 3 wks prednisone (5 mg) po twice daily q 3 wks | |||
Abratt, 2003 [62] | 451/414 | vinorelbine (30 mg/m2) iv q 3 wks hydrocortisone (40 mg) ± AGM (1000 mg)† daily | to progression |
hydrocortisone (40 mg) ± AGM (1000 mg)† daily | |||
Berry, 2001 [84] | 166/NR | paclitaxel (100 mg/m2) iv q 4 wks EMP (280 mg) po thrice daily | NR |
paclitaxel (100 mg/m2) iv q 4 wks | |||
Hudes, 1999 [61] | 201/193 | vinblastine (4 mg/m2) iv q wk for 6 of 8 wks EMP (600 mg/m2) po daily (2 or 3 divided doses) | to progression |
vinblastine (4 mg/m2) iv q wk for 6 of 8 wks | |||
Iversen, 1997 [65] | 131/129 | EMP (560 mg) po daily (2 divided doses) | as long as tolerated by patient |
placebo po daily | |||
Johansson, 1991 [66] | 105/102 | MPA (1000 mg) im daily (d1-15), then im weekly | to progression |
EMP (280 mg) po twice daily | |||
De Kernion, 1988 [67] | 220/203 | EMP (600 mg/m2) po (3 divided doses) | NR |
flutamide (0.25 gm) po thrice daily | |||
Murphy, 1979 [68] | 135/116 | EMP (600 mg/m2) po daily (3 divided doses) prednimustine (30 mg) po daily (3 divided doses) q wk | to progression |
prednimustine (30 mg) po daily (3 divided doses) q wk |
Trial | Treatment arms | Overall survival | Progression-free survival or TTP | ||||
---|---|---|---|---|---|---|---|
N | Median (mo) | Statistical comparison | N | Median (mo) | Statistical comparison | ||
Tannock, 2004 [64] | docetaxel q 3 wks prednisone | 335 | 18.9 | HR = 0.76 (95% CI, 0.62–0.94), p = 0.009 | NR | ||
docetaxel q wk prednisone | 334 | 17.4 | HR = 0.91 (95% CI, 0.75–1.11) p = 0.36 | ||||
Mitoxantrone prednisone | 337 | 16.5 | NA | ||||
Petrylak, 2004 [63] | Docectaxel EMP | 338 | 17.5 | HR = 0.80 (95% CI, 0.67–0.97) p = 0.02 | 324 | 6.3 | HR = 0.73 (95% CI, 0.63–0.86) p < 0.001 (TPP) |
Mitoxantrone prednisone | 336 | 15.6 | 324 | 3.2 | |||
Abratt, 2004 [62] | Vinorelbine hydrocortisone ± AGM | 206 | 14.7 | p = 0.95 | 206 | 3.7 | HR = 0.71 p = 0.055 (unadjusted) p = 0.005 (adjusted)* |
hydrocortisone ± AGM | 208 | 15.2 | 208 | 2.8 | |||
Berry, 2001 [84] | paclitaxel EMP | 166 | 15.1 | p = 0.11 | 166 | NR | p = 0.08 |
Paclitaxel | 12.9 | ||||||
Hudes, 1999 [61] | vinblastine EMP | 95 | 11.9 | p = 0.08 | 98 | 3.7 | p < 0.0004† (TTP) |
Vinblastine | 98 | 9.2 | 95 | 2.2 | |||
Iversen, 1997 [65] | EMP | 61 | 9.4 | p = 0.09 | 60 | 2.2 | |
Placebo | 68 | 6.1 | 67 | 5.0 | |||
Johansson, 1991 [66] | EMP | 51 | NR | p = 0.23 | 51 | NR | p = 0.28 |
MPA | 51 | 51 | |||||
De Kernion, 1988 [67] | EMP | 102 | NR | p = NS | 102 | NR | p = NS |
Flutamide | 101 | 101 | |||||
Murphy, 1979 [68] | EMP prednimustine | 54 | 9.3 | p = NS | NR | ||
prednimustine | 62 | 9.0 |
Trial | Treatment arms | PSA response* | Tumor response | ||||
---|---|---|---|---|---|---|---|
N | Response rate % | Statistical comparison | N | Objective response rate % | Statistical comparison | ||
Tannock, 2004 [64] | docetaxel q 3 wks prednisone | 291 | 45 | p < 0.001 | 141 | 12 | p = 0.1 |
docetaxel q wk prednisone | 291 | 48 | p < 0.001 | 134 | 8 | p = 0.6 | |
Mitoxantrone prednisone | 300 | 32 | NA | 137 | 7 | NA | |
Petrylak, 2004 [63] | Docetaxel EMP | 309 | 50 | p < 0.001 | 103 | 17 | p < 0.30 |
Mitoxantrone prednisone | 303 | 27 | 93 | 11 | |||
Abratt, 2004 [62] | Vinorelbine hydrocortisone ± AGM | 206 | 30.1 | p < 0.01 | 68 | 5.9(PR) | NR |
hydrocortisone ± AGM | 208 | 19.2 | 74 | 0 | |||
Berry, 2001 [84] | Paclitaxel EMP | 166 | 48 | p < 0.01 | NR | ||
Paclitaxel | 25 | ||||||
Hudes, 1999 [61] | vinblastine EMP | 87 | 25.2 | p < 0.0001 | 30 | 20 (PR) | p = 0.13 |
Vinblastine | 94 | 3.2 | 33 | 6 (PR) | |||
Iversen, 1997 [65] | EMP | 43 | 37.2 | p = 0.001 | NR | ||
Placebo | 51 | 2.0 | |||||
Johansson, 1991 [66] | EMP | NR | NR | ||||
MPA | |||||||
De Kernion, 1988 [67] | EMP | NR | 102 | 0 | p = NS | ||
Flutamide | 101 | 1.0 (PR) | |||||
Murphy, 1979 [68] | EMP prednimustine | NR | 54 | 1.9 (PR) | p = NS | ||
prednimustine | 62 | 0 |
Estramustine
Vinorelbine
Anthracenedione/anthracycline-based chemotherapy
Mitoxantrone
Trial | N randomized/evaluable | Treatment arms (dose) and schedule | Duration |
---|---|---|---|
Berry, 2002 [69] | 120/119 | mitoxantrone (12 mg/m2) iv q 3 wks prednisone (5 mg) po twice daily | 6 cycles |
prednisone (5 mg) po twice daily | |||
Kantoff, 1999 [70] | 242/242 | mitoxantrone (14 mg/m2) iv q 3 wks hydrocortisone (40 mg) po daily (two divided doses) | hydrocortisone to progression or treatment failure |
hydrocortisone (40 mg) po daily (two divided doses) | |||
Tannock, 1996 [71] | 161/161 | mitoxantrone (12 mg/m2) iv q 3 wks prednisone (5 mg) po twice daily | mitoxantrone to dose of 140 mg/m2, continuing on prednisone |
prednisone (5 mg) po twice daily | |||
Weissbach, 1998 [88] | NR/175 | epirubicin (25 mg/m2) iv q mo | NR |
EMP (560 mg) daily | |||
mitomycin C (10 mg/m2) iv q mo | |||
Anderström, 1995 [72] | 149/145 | epirubicin (20 mg/m2) iv q wk MPA (500 mg) po twice daily | epirubicin to dose of 1000 mg/m2, MPA to progression |
EMP (12 mg/kg) po daily (two divided doses) | |||
Laurie, 1992* [73] | 145/142 | In combination: 5-FU (600 mg/m2) iv q 4–5 wks doxorubicin (30 mg/m2) iv q 4–5 wks mitomycin-C (10 mg/m2) iv q 4–5 wks† | to progression |
In sequence: 5-FU (500 mg/m2) iv q 5 wk doxorubicin (50 mg/m2) iv q 3–4 wk mitomycin-C (12.5 mg/m2) iv q 4 wk | |||
Saxman, 1992 [74] | 103/103 | cyclophosphamide (500mg/m2)‡ iv q 3 wks doxorubicin (50mg/m2)‡ iv q 3 wks methotrexate (40mg/m2)‡ iv q 3 wks | to progression, doxorubicin not to exceed dose of 450mg/m2
|
cyclophosphamide (1000 mg/m2)§iv q 3 wks | |||
Murphy, 1988 [75] | 180/152 | doxorubicin (50 mg/m2) iv q 3 wks cyclophosphamide (500 mg/m2) iv q 3 wks | to progression |
cisplatin (50 mg/m2) iv q 3 wks 5-FU (500 mg/m2) iv q 3 wks cyclophosphamide (500 mg/m2) iv q 3 wks | |||
methotrexate (100 mg/m2) iv (2 divided doses) q 2 wks | |||
Stephens, 1984 [76] | 158/137 | doxorubicin (40 mg/m2)¶iv q 3 wks cyclophosphamide (200 mg/m2)¶iv q 3 wks | doxorubicin to dose of 450 mg/m2, continuing on cyclophosphamide or hydroxyurea to progression |
hydroxyurea (3600 mg/m2) po twice q wk |
Trial | Treatment arms | Overall survival | Progression-free survival or TTP | ||||
---|---|---|---|---|---|---|---|
N | Median (mo) | Statistical comparison | N | Median (mo) | Statistical comparison | ||
Berry, 2002 [69] | mitoxantrone prednisone | 56 | 23 | p = 0.48 | 56 | 8.1 | p = 0.018 (TTP) |
prednisone | 63 | 19 | 63 | 4.1 | |||
Kantoff, 1999 [70] | mitoxantrone | 119 | 12.3 | p = 0.77 | 119 | 3.7 | p = 0.02 (TTP) |
hydrocortisone | 123 | 12.6 | 123 | 2.3 | |||
Tannock, 1996 [71] | mitoxantrone prednisone | 80 | NR | p = 0.27 | NR | ||
prednisone | 81 | ||||||
Weissbach, 1998 [88] | epirubicin | 61 | NR by treatment group | 61 | NR by treatment group | "TTF was longer with mitomycin C vs. EMP (p = 0.037); and vs. epirubicin (p = 0.039) | |
EMP | 54 | 54 | |||||
mitomycin C | 60 | 60 | |||||
Anderström, 1995 [72] | epiribucin MPA | 73 | 11.5 | p = NS | 73 | 7.6 | p = 0.013 (TTP) |
EMP | 72 | 9.5 | 72 | 4.3 | |||
Laurie, 1992 [73] | 5-FU doxorubicin mitomycin C (combined) | 70 | 8.7 | p = 0.025 | NR | ||
5-FU doxorubicin mitomycin C (sequential) | 72 | 7.1 | |||||
Saxman, 1992 [74] | cyclophosphamide doxorubicin methotrexate | 26 high PS 24 low PS | 9.5 6 | p = 0.93 p = 0.51 p = 0.7 (unstratified) | 50 | 6.2* | p = 0.07 (TTP) |
cyclophosphamide | 26 high PS 27 low PS | 9 5 | 53 | 4.4* | |||
Murphy, 1988 [75] | doxorubicin cyclophosphamide | 54 | NR | p = NS | 54 | NR | p = NS |
cisplatin 5-FU cyclophosphamide | 46 | 46 | |||||
methotrexate | 52 | 52 | |||||
Stephens, 1984 [76] | doxorubicin cyclophosphamide | 68 | 6.8 | p = NS | NR | ||
hydroxyurea | 69 | 7 |
Trial | Treatment arms | PSA response* | Tumor response | ||||
---|---|---|---|---|---|---|---|
N | Response rate % | Statistical comparison | N | Objective response rate % | Statistical comparison | ||
Berry, 2002 [69] | mitoxantrone prednisone | 56 | 48† | p = 0.007 | 8 | 25 (PR) | p = NR |
prednisone | 63 | 24† | 9 | 22 (PR) | |||
Kantoff, 1999 [70] | mitoxantrone hydrocortisone | 96 | 18.7 | p = 0.41 | 116 | 7 (PR) | p = 0.38 |
hydrocortisone | 91 | 14.3 | 118 | 4 (PR) | |||
Tannock, 1996 [71] | mitoxantrone prednisone | 57 | 33 | p = 0.11 | NR | ||
prednisone | 54 | 22 | |||||
Weissbach, 1998 [88] | mitomycin C | NR | 60 | 22 | NR | ||
epirubicin | 61 | 11 | |||||
EMP | 55 | 9 | |||||
Anderström, 1995 [72] | epiribucin MPA | NR | NR | ||||
EMP | |||||||
Laurie, 1992 [73] | 5-FU doxorubicin mitomycin-C (combined) | NR | 70 | 14 | NR | ||
5-FU doxorubicin mitomycin-C (sequential) | 72 | 18 | |||||
Saxman, 1992 [74] | cyclophosphamide doxorubicin methotrexate | NR | 16 | 18.8 (PR) | NR | ||
cyclophosphamide | 16 | 6 (PR) | |||||
Murphy, 1988 [75] | doxorubicin cyclophosphamide | NR | 54 | 1 (PR) | p = NS | ||
cisplatin 5-FU cyclophosphamide | 46 | 0 | |||||
methotrexate | 52 | 0 | |||||
Stephens, 1984 [76] | doxorubicin cyclophosphamide | NR | 19 | 32 | p = 0.05 | ||
hydroxyurea | 24 | 4 |
Doxorubicin and epirubicin
Other cytotoxic agents
Trial | N randomized/Evaluable | Treatments (dose) and schedule | Duration |
---|---|---|---|
Weissbach, 1998 [88] | NR/175 | epirubicin (25 mg/m2) iv q mo | NR |
EMP (560 mg) daily | |||
mitomycin C (10 mg/m2) iv q mo | |||
Newling, 1993 [77] | 171/161 | mitomycin-C (15 mg/m2) iv q 6 wks | to progression |
EMP (560 to 700 mg)* po daily | |||
Murphy, 1988 [75] | 180/152 | doxorubicin (50 mg/m2) iv q 3 wks cyclophosphamide (500 mg/m2) iv q 3 wks | to progression |
cisplatin (50 mg/m2) iv q 3 wks 5-FU (500 mg/m2) iv q 3 wks cyclophosphamide (500 mg/m2) iv q 3 wks | |||
methotrexate (100 mg/m2) iv (2 divided doses) q 2 wks | |||
Loening, 1983 [78] | 189/158 | methotrexate (100 mg/m2) iv (two divided doses) q wk | 12 wks |
cisplatin (60 mg/m2) iv (d1,4,21,24), then once monthly | |||
EMP (600 mg/m2) po daily (3 divided doses) |
Non-cytotoxic agents
Trial | N randomized/evaluable | Treatments (dose) and schedule | Duration |
---|---|---|---|
Carducci, 2004 [85] | 809/809 | atrasentan po (10 mg) | NR |
placebo | |||
Carducci, 2003 [79] | 288/288 | atrasentan (2.5 mg) po daily | to progression |
atrasentan (10 mg) po daily | |||
placebo | |||
Small, 2003 [86] | 127/127 | APC8015 iv q 2 wks × 3 | to progression |
placebo | |||
Small, 2002 [81] | 390/390 | suramin (3.192 mg/m2)* iv | 3 cycles (12 weeks) |
suramin (5.320 mg/m2)* iv | |||
suramin (7.661 mg/m2)* iv | |||
Ahmann, 2001 [87] | 553/406† | prinomastat (5 mg) po twice daily mitoxantrone (12 mg/m2) iv q 3 wks prednisone (5 mg) po twice daily | NR |
prinomastat (10 mg) po twice daily mitoxantrone (12 mg/m2) iv q 3 wks prednisone (5 mg) po twice daily | |||
mitoxantrone (12 mg/m2) iv q 3 wks prednisone (5 mg) po twice daily placebo | |||
Small, 2000 [82] | 460/458 | suramin d1: 1000 mg/m2 2-hr iv d2-5: 400 mg/m2, 300 mg/m2, 250 mg/m2, and 200 mg/m2 iv, respectively d8,11,15,19: 275 mg/m2 iv for 2 wks d22,29,36,43,50,57,64,71,78: 275 mg/m2 iv wks 4–12 hydrocortisone (40 mg) po daily | to progression or unacceptable toxicity |
hydrocortisone po daily placebo | |||
Debruyne, 1998 [83] | 321/321 | liarozole (300 mg) twice daily | to progression or unacceptable toxicity |
CPA (100 mg) twice daily |
Trial | Treatment arms | Overall survival | Progression-free survival or TTP or FFS | ||||
---|---|---|---|---|---|---|---|
N | Median (mo) | Statistical comparison | N | Median (mo) | Statistical comparison | ||
Carducci, 2004 [85] | Atrasentan | NR | 408 | NR | HR for TTP = 1.14 (95% CI, 0.98–1.34) p = 0.091 | ||
placebo | 401 | ||||||
Carducci, 2003 [79] | atrasentan 10 mg | NR | 89 | 6.5 | p = 0.13 (TTP) | ||
atrasentan 2.5 mg | 95 | 6.4 | p = 0.29 (TTP) | ||||
placebo | 104 | 4.9 | NA | ||||
Small, 2003 [86] | APC8015 | NR | 82 | NR | HR for TTP = 1.39 (95% CI, 0.95–2.04) p = 0.085 | ||
placebo | 45 | ||||||
Small, 2002 [81] | suramin (3.192 g/m2) | 128 | 16 | p = 0.49 | 128 | NR | p = NS |
suramin (5.320 g/m2) | 124 | 14 | 124 | ||||
suramin (7.661 g/m2) | 120 | 13 | 120 | ||||
Ahmann, 2001 [87] | prinomastat (5 mg) mitoxantrone prednisone | 134 | 15.1 | p = NS | 134 | 6 | p = NS |
prinomastat (10 mg) mitoxantrone prednisone | 134 | 14.7 | 134 | 4.7 | |||
mitoxantrone prednisone placebo | 138 | 14.8 | 138 | 6 | |||
Small, 2000 [82] | suramin hydrocortisone | 228 | 10.2 | p = NS | 228 | NR | RR for TTP = 1.51 (95% CI, 1.22–1.85) p = 0.0003 |
placebo hydrocortisone | 230 | 10 | 230 | ||||
Debruyne, 1998 [83] | liarozole | 160 | 10.3 | p = 0.52 HR = 0.74* (95% CI, 0.56–0.99) p = 0.039 | 160 | 4.9 | p = NS |
CPA | 161 | 10.3 | 161 | 4.6 |
Trial | Treatment arms | PSA response* | Tumor response | ||||
---|---|---|---|---|---|---|---|
N | Response rate %, unless otherwise specified | Statistical comparison | N | Objective response rate % | Statistical comparison | ||
Carducci, 2004 [85] | Atrasentan | 408 | "smaller mean ↑ with atrasentan vs. placebo" | p = 0.025 | NR | ||
placebo | 401 | ||||||
Carducci, 2003 [79] | atrasentan 10 mg | median time-to-PSA progression: | NR | ||||
89 | 5.5 mo | p = 0.002 | |||||
atrasentan 2.5 mg | 95 | 5 mo | p = 0.055 | ||||
placebo | 104 | 2.5 mo | NA | ||||
Small, 2003 [86] | APC8015 | 82 | 4.9 | NR | NR | ||
placebo | 45 | 0 | |||||
Small, 2002 [81] | suramin (3.192 g/m2) | 128 | 24 | p = 0.08 (test for trend) | 128 | 9 | p = 0.104 (test for trend) |
suramin (5.320 g/m2) | 124 | 28 | 124 | 7 | |||
suramin (7.661 g/m2) | 120 | 34 | 120 | 15 | |||
Ahmann, 2001 [87] | prinomastat (5 mg) mitoxantrone prednisone | 134 | 17† | p = NS | NR | ||
prinomastat (10 mg) mitoxantrone prednisone | 134 | 18† | |||||
mitoxantrone prednisone placebo | 138 | 14† | |||||
Small, 2000 [82] | suramin hydrocortisone | 228 | 33 | p = 0.01 | 76 | 4 (PR) | NR |
placebo hydrocortisone | 230 | 16 | 80 | 0 | |||
Debruyne, 1998 [83] | liarozole | 160 | 20 | p < 0.001 | NR | ||
CPA | 161 | 4 |