Background
Methods
Search strategy
Selection criteria
Data collection
Statistical analysis
Results
Selection of the trials
Characteristics of the trials included in the present analysis
Trial | No. of pts | Regimens (per arm) | No. of pts (per arm) | Male | Median age (range)(y) | PS 0-2/KPS≥50 | M* | |
---|---|---|---|---|---|---|---|---|
Gong JF | 40 | palliative | Gem-X** | 25 | 56% | 63 (45-76) | UK | UK |
2007[8] | Gem | 15 | 66.7% | 63 (45-76) | ||||
Reni M | 104 | first line | PEFG | 52 | 46.2% | 62 (37-69) | 100% | 71% |
2005[9] | Gem | 47 | 40.7% | 59 (25-69) | 100% | 56% | ||
Gem versus Gem plus fluoropyrimidine | ||||||||
Cunningham D | 533 | first line | Gem/Cap | 267 | 60% | 62 (37-82) | 100% | 70% |
2009[10] | Gem | 266 | 58% | 62 (26-83) | 100% | 71% | ||
Bernhard J | 319 | palliative | Gem/Cap | 160 | 54% | 62 (27-83) | 100% | 80% |
2008[11] | Gem | 159 | 53% | 62 (36-84) | 100% | 79% | ||
Scheithauer W | 83 | first line | Gem/Cap | 41 | 66% | 64 (40-75) | 100% | UK |
2003[12] | Gem | 42 | 55% | 66 (39-75) | 100% | |||
Berlin JD | 327 | first line | Gem/5-FU | 160 | 51.8% | 65.8 (28-84) | 100% | 89.4% |
2002[13] | Gem | 162 | 53.7% | 64.3 (33-85) | 100% | 90.1% | ||
Di Costanzo F | 94 | first line | Gem/5-FU | 45 | 63% | 62 (44-75) | 100% | 67% |
2005[14] | Gem | 49 | 48% | 64 (34-75) | 100% | 73% | ||
Riess H[15] | 473 | first line | Gem/5-FU | 235 | UK | UK | 100% | UK |
2005 | Gem | 238 | 100% | |||||
Gem versus Gem plus platinum | ||||||||
Louvet C | 313 | first line | Gem/Oxa | 157 | 60% | 61 (35-77) | 100% | 68% |
2005[16] | Gem | 156 | 53% | 60 (22-75) | 100% | 70% | ||
Poplin E | 824 | first line | Gem/Oxa | 272 | 45.6% | 63 (29-96) | 99.6% | 89.3% |
2009[17] | Gem | 275 | 56.4% | 63 (31-88) | 100% | 90.2% | ||
Gem FDR | 277 | 57.8% | 62 (36-87) | 99.6% | 88.8% | |||
Yan ZC | 60 | first line | Gem/Oxa | 30 | 63.3% | 58 (23-75) | 31.7% | UK |
2007[18] | Gem | 30 | 63.3% | 58 (23-75) | 31.7% | UK | ||
Colucci G | 400 | first line | Gem/DDP | 201 | 62.2% | 63 (35-75) | 100% | 84.6% |
2010[19] | Gem | 199 | 56.8% | 63 (37-75) | 100% | 82.9% | ||
Colucci G | 107 | first line | Gem/DDP | 53 | 66% | 60 (33-71) | 100% | 62% |
2002[20] | Gem | 54 | 50% | 63 (43-75) | 100% | 54% | ||
Wang XY | 42 | first line | Gem/DDP | 22 | 68.2% | 65 (37-76) | 100% | 68.2% |
2002[21] | Gem | 20 | 70.0% | 57 (35-60) | 100% | 50% | ||
Heinemann V | 195 | first line | Gem/DDP | 98 | 65.3% | 64 (37-82) | 100% | 80% |
2006[22] | Gem | 97 | 61.9% | 66 (43-85) | 100% | 78.9% | ||
Palmer DH | 50 | neoadjuvant | Gem/DDP | 26 | 50% | 66 (47-78) | 100% | UK |
2007[23] | Gem | 24 | 54% | 66 (40-79) | 100% | |||
Li CP | 46 | first line | Gem/DDP | 21 | UK | UK | UK | UK |
2004[24] | Gem | 25 | ||||||
Kulke MH | 259 | first line | Gem/DDP | 66 | 56% | 59 (36-84) | 100% | UK |
2009[25] | Gem FDR | 64 | 66% | 59 (31-81) | 100% | UK | ||
Gem/Doc | 65 | 62% | 63 (41-79) | 100% | UK | |||
Gem/CPT-11 | 64 | 68% | 61 (32-77) | 100% | UK | |||
Viret F | 83 | first line | Gem/DDP | 42 | UK | 62 | 100% | 81% |
2004[26] | Gem | 41 | UK | 63 | 100% | 78% | ||
Gem versus camptothecin | ||||||||
Stathopoulos GP | 130 | first line | Gem/CPT-11 | 60 | 65% | 64 (31-84) | 100% | 78% |
2006[27] | Gem | 70 | 60% | 64 (44-83) | 100% | 86% | ||
Rocha Lima CM | 360 | first line | Gem/CPT-11 | 180 | 57.2% | 63 (39-81) | 97.2% | 82.2% |
2004[28] | Gem | 180 | 53.3% | 60 (32-83) | 93.9% | 80.6% | ||
Abou-Alfa GK | 349 | first line | Gem/exatecan | 175 | 53% | 63 (36-85) | 99% | 79% |
2006[29] | Gem | 174 | 57% | 62 (30-84) | 100% | 78% | ||
Gem versus pemetrexed | ||||||||
Oettle H | 565 | palliative | Gem/Pem* | 283 | 60.4% | 63 (27-82) | 98.9% | 90.1% |
2005[30] | Gem | 282 | 53.5% | 63 (28-82) | 98.9% | 91.1% | ||
Gem versus Gem plus targeted therapy | ||||||||
Moore MJ | 569 | palliative | Gem/erlotinib | 285 | 47.7% | 64 (38-84) | 99.6% | 76.5% |
2007[31] | Gem | 284 | 57% | 64 (36-92) | 100% | 75% | ||
Van Cutsem E | 688 | first line | Gem/tipifarnib | 341 | 57% | 61 (29-89) | 100% | 76% |
2004[32] | Gem | 347 | 58% | 62 (30-88) | 100% | 77% | ||
Philip PA | 743 | palliative | Gem/Cetuximab | 372 | 51% | 63.7 | 100% | 79% |
2010[33] | Gem | 371 | 54% | 64.3 | 100% | 78% | ||
Saif MW | 135 | palliative | Gem/LY293111 | 67 | 60% | 62(33-82) | 99% | 87% |
2009[34] | Gem | 66 | 60% | 62(34-85) | 99% | 90% | ||
Spano JP | 103 | palliative | Gem/axitinib | 69 | 51% | 65(44-81) | 100% | 58% |
2008[35] | Gem | 34 | 47% | 61(36-78) | 100% | 56% | ||
Bramhall SR | 239 | first line | Gem/marimastat | 120 | 57.5% | 62 (32-83) | 100% | 59% |
2002[36] | Gem | 119 | 59.7% | 62 (37-85) | 100% | 62% | ||
Kindler HL | 602 | first line | Gem/Bev | 302 | 58% | 64 (26-88) | 100% | 84% |
2010[37] | Gem | 300 | 51% | 65 (35-86) | 100% | 85% | ||
Richards DA | 174 | first line | Gem/CI-994 | 86 | 59.3% | 62 (32-82) | 100% | 82.6% |
2006[38] | Gem | 88 | 60.2% | 65 (36-83) | 100% | 83% | ||
Friess H | 89 | first line | Gem/Cilengitide | 46 | 57% | 68 (40-80) | 100% | 93% |
2006[39] | Gem | 43 | 42% | 66 (56-80) | 100% | 90% | ||
the others | ||||||||
Cascino S | 84 | first line | C-225/Gem/DDP | 42 | 69% | 61 (38-78) | 100% | 73.8% |
2008[40] | Gem/DDP | 42 | 52% | 64 (40-76) | 100% | 71.4% | ||
Vervenne W | 607 | first line | Gem/erlotinib/Bev | 306 | 57% | 62 | 100% | 100% |
2008[41] | Gem/erlotinib | 301 | 62% | 61 | 100% | 100% | ||
Boeck S | 190 | first line | Cap/Oxa | 61 | 65% | 62 (37-74) | 100% | 63% |
2007[42] | Gem/Cap | 64 | 57% | 63 (47-75) | 100% | 69% | ||
Gem/Oxa | 63 | 70% | 63 (45-75) | 100% | 71% |
Trial | Arm | Regimens |
---|---|---|
Gong JF 2007 | Gem/X | Gem 1,000 mg/m2 d1,8; 5-FU 425-600 mg/m2 d1-5, or DDP 30-37.5 mg/m2 d1-2, or Oxa 85-130 mg/m2 d1, or Cap 1 000 mg/m2 bid d1-14, q3w. |
Gem | Gem 1,000 mg/m2 weekly × 7 followed by a 2-week rest, then weekly for 3 weeks, q4w. | |
Reni M 2005 | PEFG | DDP 40 mg/m2 d1, EPI 40 mg/m2 d1, Gem 600 mg/m2 d1,8, 5-FU 200 mg/m2 d1-28, q4w. |
Gem | Gem 1,000 mg/m2 weekly × 7 followed by a 2-week rest, then weekly for 3 weeks, q4w. | |
Gem versus Gem plus fluoropyrimidine | ||
Cunningham D | Gem/Cap | Gem 1,000 mg/m2 weekly for 3 weeks; Cap 830 mg/m2 bid po for 3 weeks, q4w |
2009 | Gem | Gem 1,000 mg/m2 weekly × 7 followed by 1-week rest, then weekly for 3 weeks, q4w. |
Bernhard J 2008 | Gem/Cap | Gem 1,000 mg/m2 d1,8; Cap 650 mg/m2 bid po d1-14, q3w. |
Gem | Gem 1,000 mg/m2 weekly × 7 followed by 1-week rest, then weekly for 3 weeks, q4w. | |
Scheithauer | Gem/Cap | Gem 2200 mg/m2 d1, Cap 2500 mg/m2 d1-7, q2w. |
W 2003 | Gem | Gem 2200 mg/m2 d1, q2w. |
Berlin JD 2002 | Gem/5-FU | Gem 1,000 mg/m2 weekly, 5-FU 600 mg/m2 weekly for 3 weeks, q4w. |
Gem | Gem 1,000 mg/m2 weekly for 3 weeks, q4w. | |
Di Costanzo | Gem/5-FU | Gem was combined with 5-FU 200 mg/m2 for 6 weeks in the first cycle, followed by a week of rest; then for 3 weeks, q4w. |
F 2005 | Gem | Gem 1,000 mg/m2 weekly × 7 followed by a 2-week rest, then weekly for 3 weeks, q4w. |
Riess H 2005 | GFF | Gem 1,000 mg/m2, 5-FU 750 mg/m2, folinic acid 200 mg/m2 d1,8,15,22, q6w. |
Gem | Gem 1,000 mg/m2 weekly × 7 followed by a 2-week rest, then weekly for 3 weeks, q4w. | |
Gem versus Gem plus platinum | ||
Louvet C 2005 | Gem/Oxa | Gem 1,000 mg/m2 d1, Oxa 100 mg/m2 d2, q2w. |
Gem | Gem 1,000 mg/m2 weekly × 7 followed by 1-week rest, then weekly for 3 weeks, q4w. | |
Poplin E 2009 | Gem/Oxa | Gem 1,000 mg/m2 d1, Oxa100 mg/m2 d2, q2w. |
Gem | Gem 1,000 mg/m2 weekly × 7 followed by 1-week rest, then weekly for 3 weeks, q4w. | |
Gem FDR | Gem 1,500 mg/m2 administered as a 150 minutes infusion d1,8,15, q4w. | |
Yan ZC 2007 | Gem/Oxa | Gem 1,000 mg/m2 d1, Oxa 100 mg/m2 d2, q2w. |
Gem | Gem 1,000 mg/m2 d1,8,15, q4w. | |
Colucci G 2010 | Gem/DDP | Gem 1,000 mg/m2 weekly × 7 followed by 1-week rest, then weekly for 3 weeks, q4w; DDP 25 mg/m2 added weekly to Gem. |
Gem | Gem 1,000 mg/m2 weekly × 7 followed by 1-week rest, then weekly for 3 weeks, q4w. | |
Colucci G 2002 | Gem/DDP | Gem 1000 mg/m2 weekly × 7 followed by 2-week rest, DDP 25 mg/m2 per week 1 hour before Gem. |
Gem | Gem 1,000 mg/m2 weekly × 7 followed by 2-week rest, then weekly for 3 weeks, q4w. | |
Wang XY 2002 | Gem/DDP | Gem 1 000 mg/m2 d1,8,15; DDP 60 mg/m2 on d15, q4w. |
Gem | Gem 1,000 mg/m2 weekly × 7 followed by 1-week rest, then weekly for 3 weeks, q4w. | |
Heinemann V 2006 | Gem/DDP | Gem 1,000 mg/m2, DDP 50 mg/m2 d1,15, q4w. |
Gem | Gem 1,000 mg/m2 d1,8,15, q4w. | |
Palmer DH 2007 | Gem/DDP | Gem 1000 mg/m2 every 7 days for 43 days, followed immediately by DDP 25 mg/m2 |
Gem | Gem 1000 mg/m2 every 7 days for 43 days | |
Li CP 2004 | Gem/DDP | Gem 1000 mg/m2/week and DDP 25 mg/m2/week × 3 every 4 weeks |
Gem | Gem 1000 mg/m2 × 3 every 4 weeks | |
Kulke MH 2009 | Gem/DDP | Gem 1,000 mg/m2 d1,8,15; DDP 50 mg/m2 d1,15, q4w. |
Gem FDR | Gem 1,500 mg/m2 at a rate of 10 mg/m2/min d1,8,15, q4w. | |
Gem/Doc | Gem 1,000 mg/m2; Doc 40 mg/m2 d1,8, q3w. | |
Gem/CPT-11 | Gem 1,000 mg/m2; irinotecan 100 mg/m2 d1,8, q3w. | |
Viret F 2004 | Gem/DDP | Gem 1000 mg/m2 d1,8,15; DDP 75 mg/m2 d15, q4w. |
Gem | Gem 1000 mg/m2 weekly × 7 followed by 1 week of rest, then weekly for 3 weeks, q4w | |
Gem versus camptothecin | ||
Stathopoulos GP 2006 | Gem/CPT-11 | Gem d1,8; CPT-11 300 mg/m2 d8, q3w. |
Gem | Gem 900 mg/m2 d1,8,15, q4w. | |
Rocha Lima CM 2004 | Gem/CPT-11 | Gem 1,000 mg/m2 and CPT-11 100 mg/m2 given weekly for 2 weeks every 3-week cycle. |
Gem | Gem 1,000 mg/m2 weekly × 7 followed by 1-week rest, then weekly for 3 weeks, q4w. | |
Abou-Alfa GK 2006 | Gem/Exat | Exatecan 2.0 mg/m2 and Gem 1,000 mg/m2 were administered on days 1 and 8, q3w. |
Gem | Gem 1,000 mg/m2 weekly × 7 followed by 1-week rest, then weekly for 3 weeks, q4w. | |
Gem versus pemetrexed | ||
Oettle H 2005 | Gem/Pem | Gem 1,250 mg/m2 d1,8; pemetrexed 500 mg/m2 d8, q3w. |
Gem | Gem 1,000 mg/m2 d1,8,15, q4w. | |
Gem versus Gem plus targeted therapy | ||
Moore MJ 2007 | Gem/Erlo | Gem 1,000 mg/m2 weekly × 7 followed by 1-week rest, then weekly for 3 weeks, q4w; Erlotinib 100 or 150 mg/d po |
Gem | Gem 1,000 mg/m2 weekly × 7 followed by 1-week rest, then weekly for 3 weeks, q4w | |
Van Cutsem E 2004 | Gem/Tipi | Gem 1,000 mg/m2 weekly × 7 followed by 1-week rest, then weekly for 3 weeks, q4w; Tipifarnib 200 mg bid po continuously; |
Gem | Gem 1,000 mg/m2 weekly × 7 followed by 1-week rest, then weekly for 3 weeks, q4w | |
Philip PA 2010 | Gem/C-225 | Gem 1,000 mg/m2 weekly × 7 followed by 1-week rest, then weekly for 3 weeks, q4w; |
Cetuximab 400 mg/m2 on week 1, followed by weekly 250 mg/m2. | ||
Gem | Gem 1,000 mg/m2 weekly × 7 followed by 1-week rest, then weekly for 3 weeks, q4w | |
Saif MW 2009 | Gem/LY | Gem 1000 mg/m2 d1,8,15, q4w; continuously administered LY 600 mg twice daily. |
Gem | Gem 1000 mg/m2 d1,8,15, q4w. | |
Spano JP 2008 | Gem/Axitinib | Gem 1000 mg/m2 d1,8,15, q4w; Axitinib 5 mg twice daily. |
Gem | Gem 1000 mg/m2 d1,8,15, q4w. | |
Bramhall SR 2002 | Gem/Marimastat | Gem 1,000 mg/m2 weekly × 7 followed by 1-week rest, then weekly for 3 weeks, q4w; Marimastat 25 mg bid po. |
Gem | Gem 1,000 mg/m2 weekly × 7 followed by 1-week rest, then weekly for 3 weeks, q4w. | |
Kindler HL 2010 | Gem/Bev | Gem 1,000 mg/m2 d1,8,15; Bev 10 mg/kg d1,15; q4w. |
Gem | Gem 1,000 mg/m2 d1,8,15; q4w. | |
Richards DA 2006 | Gem/CI-994 | Gem 1000 mg/m2 d1,8,15; CI-994 6 mg/m2 d1-21; q4w. |
Gem | Gem 1000 mg/m2 d1,8,5; q4w. | |
Friess H 2006 | Gem/Cile | Gem 1000 mg/m2 d1,8,15; Cilengitide 600 mg/m2 twice weekly; q3w. |
Gem | Gem 1000 mg/m2 d1,8,15; q3w. | |
the others | ||
Cascino S 2008 | C-225/Gem/DDP | Cetuximab 250 mg/m2 weekly, after a loading dose of 400 mg/m2; Gem 1000 mg/m2 and DDP 35 mg/m2 on d1,8; q3w. |
Gem/DDP | Gem 1000 mg/m2 and DDP 35 mg/m2 on d1,8; q3w. | |
Vervenne W 2008 | Gem/Erlo/Bev | Gem 1,000 mg/m2 weekly × 7 during first 8 weeks, then for 3 weeks, q4w. |
Erlotinib 100 mg/d po daily; Bevacizumab 5 mg/kg q2w. | ||
Gem/Erlo | Gem 1,000 mg/m2 weekly × 7 for 7 weeks followed by 1-week rest, then weekly for 3 weeks, q4w; Erlotinib 100 mg/d po daily. | |
Boeck S 2007 | Cap/Oxa | Cap 1000 mg/m2 bid d1-14; Oxa 130 mg/m2 d1. |
Gem/Cap | Gem 1,000 mg/m2 d1,8; Cap 825 mg/m2 bid d1-14 | |
Gem/Oxa | Gem 1,000 mg/m2 d1,8; Oxa 130 mg/m2 d8 |
Trials comparing single-agent gemcitabine with gemcitabine combined with other cytotoxic agents
Trials comparing gemcitabine alone with gemcitabine plus fluoropyrimidine
Trials comparing gemcitabine alone with gemcitabine plus platinum
Trials comparing gemcitabine alone with gemcitabine plus camptothecin
Trials comparing gemcitabine monotherapy with gemcitabine plus other agents
Trials comparing gemcitabine monotherapy with gemcitabine plus targeted therapy
Trial | Regimen (per arm) | No. of pts | Median OS (mons) | HR (95% CI) | p value | Median PFS/TTP (mons) | HR (95%CI) | p value |
---|---|---|---|---|---|---|---|---|
Moore MJ 2007 | Gem/erlotinib | 285 | 6.24 | 0.82 | 0.038* | 3.75 | 0.77 | 0 .004* |
Gem | 284 | 5.91 | (0.69-0.99) | 3.55 | (0.64-0.92) | |||
Philip A 2010 | Gem/C-225 | 372 | 6.3 | 1.06 | 0 .23 | 3.4 | 1.07 | 0.18 |
Gem | 371 | 5.9 | (0.91-1.23) | 3.0 | (0.93-1.24) | |||
Van Cutsem E 2004 | Gem/tipifarnib | 341 | 6.4 | 1.03 | 0 .75 | 3.7 | 1.03 | 0 .72 |
Gem | 347 | 6.1 | (0.86-1.23) | 3.6 | (0.87-1.22) | |||
Saif W 2009 | Gem/LY293111 | 67 | 7.1 | UA | > 0.05 | 3.7 | UA | > 0.05 |
Gem | 66 | 8.3 | 3.4 | |||||
Spano JP 2008 | Gem/axitinib | 69 | 6.9 | 0·71 | UA | 4.2 | UA | |
Gem | 34 | 5.6 | (0.44-1.13) | 3.7 | (0.43-1.45) | |||
Bramhall SR 2002 | Gem/marimastat | 120 | 5.5 | 0.99 | 0.95 | 3.1 | 0.68 | 0.68 |
Gem | 119 | 5.5 | (0.76-1.30) | 3.2 | (0.73-1.23) | |||
Kindler HL 2010 | Gem/bevacizumab | 302 | 5.8 | 1.004 | 0.95 | 3.8 | UA | 0.075 |
Bev | 300 | 5.9 | (0.88-1.24) | 2.9 | ||||
Richards DA 2006 | Gem/CI-994 | 85 | 6.5 | 0.980 | 0.904 | 3.1 | 0.837 | 0.304 |
Gem | 88 | 7.1 | (0.701-1.370) | 3.4 | (0.596-1.175) | |||
Friess H 2006 | Gem/cilengitide | 46 | 6.8 | UA | > 0.05 | 3.7 | UA | > 0.05 |
Gem | 43 | 7.8 | 3.8 |