Table 3.
Summary of randomized controlled trials concerning first-line chemotherapy in patients with locally advanced or metastatic pancreatic carcinomas.
| Trial | Year | Country/Region | N | Regimens | Outcomes |
|---|---|---|---|---|---|
| Burris [47] | 1997 | USA and Canada | 126 | Gemcitabine (n = 63) vs. 5-FU (n = 63) | mOS 5.65 mo vs. 4.41 mo (p = 0.0025); 1-year OS 18% vs. 2%; mPFS 2.33 mo vs. 0.92 mo (p = 0.0002); 1-year PFS 9% vs. 5%; clinical benefit response 23.8% vs. 4.8 (p = 0.0022) |
| Huguier [48] | 2001 | France | 45 | 5-FU + leucovorin + cisplatin (n = 22) vs. best supportive care (n = 23) | mOS 8.6 mo vs. 7.0 mo |
| Ducreux [49] | 2002 | France | 207 | 5-FU + cisplatin (n = 104) vs. 5-FU (n = 103) | response 12% vs. 0% (p < 0.01); 1-year OS 17% vs. 9% (p = 0.10); 1-year PFS 10% vs. 0% (p = 0.0001) |
| Colucci [50] | 2002 | Italy | 107 | Gemcitabine + cisplatin (n = 53) vs. gemcitabine (n = 54) | mOS 30 weeks vs. 20 weeks (p = 0.43); response 26.4% vs. 9.2% (p = 0.02); mTTP (time to progression) 20 weeks vs. 8 weeks (p = 0.048) |
| Scheithauer [51] | 2003 | Austria | 83 | Gemcitabine + capecitabine (2500 mg/m2 qd 1/2 weeks) (n = 41) vs. gemcitabine (high-dose intense) (n = 42) | mOS 9.5 mo vs. 8.2 mo; 1-year OS 31.8% vs. 37.2%; mPFS 5.1 mo vs. 4.0 mo; response 17% vs. 14%; clinical benefit 48.4% vs. 33%; P values not reported |
| Tempero [52] | 2003 | USA and Netherlands | 92 | dose-intense gemcitabine (n = 49) vs. fixed dose rate gemcitabine (n = 43) | mOS 5.0 mo vs. 8.0 mo (p = 0.013); 1-year OS 9% vs. 28.8% (p = 0.014); 2-year OS 2.2% vs. 18.3% (p = 0.007); mPFS 1.9 mo vs. 3.4 mo (p = 0.68) mTTF (time to treatment failure) 1.8 mo vs. 2.1 mo (p = 0.09) |
| Ducreux [53] | 2004 | France | 63 | 5-FU + oxaliplatin (n = 31) vs. 5-FU (n = 15) vs. oxaliplatin (n = 17) | mOS 9.0 mo vs. 2.4 mo vs. 3.4 mo; mPFS 4.2 mo vs. 1.5 mo vs. 2.0 mo; response 10% vs. 0% vs. 0%; stable 48% vs. 20% vs. 12% |
| Louvet (GERCOR GISCAD) [54] | 2005 | France and Italy | 326 | Gemcitabine + oxaliplatin (n = 157) vs. gemcitabine (n = 156) | mOS 9.0 mo vs. 7.1 mo (p = 0.13); 1-year OS 34.7% vs. 27.8% (p = 0.22); mPFS 5.8 mo vs. 3.7 mo (p = 0.04); response 26.8% vs. 17.3% (p = 0.04); clinical benefit 38.2% vs. 26.9% (p = 0.03) |
| Heinemann [55] | 2006 | Germany | 195 | Gemcitabine + cisplatin (n = 98) vs. gemcitabine (n = 97) | mOS 7.5 mo vs. 6.0 mo (p = 0.15); 1-year OS 25.3% vs. 24.7% (p = 0.21); mPFS 5.3 mo vs. 3.1 mo (p = 0.053); response 10.2% vs. 8.2% ns; stable 60.2% vs. 40.2% (p < 0.001) |
| Moore (NCIC CTG PA.3) [56] | 2007 | International | 569 | Gemcitabine plus erlotinib (n = 285) vs. gemcitabine plus placebo (n = 284) | mOS 6.24 mo vs. 5.91 mo (p = 0.038); 1-year OS 23% vs. 17% (p = 0.023); mPFS 3.75 mo vs. 3.55 mo (p = 0.004); control 57.5% vs. 49.2% (p = 0.07) |
| Herrmann [57] (SAKK 44/00-CECOG/PAN.1.3.001) | 2007 | Europe | 319 | Gemcitabine + capecitabine (650 mg/m2 bid po 2/3 weeks) (n = 160) vs. gemcitabine (standard dose) (n = 159) | mOS 8.4 mo vs. 7.2 mo (p = 0.234); 1-year OS 32% vs. 30%; mPFS 4.3 mo vs. 3.9 mo (p = 0.103); response 10.0% vs. 7.8%; clinical benefit 19% vs. 20% |
| Boeck [58] | 2008 | Germany | 190 | Capecitabine plus oxaliplatin (n = 61) vs. capecitabine plus gemcitabine (n = 64) vs. gemcitabine plus oxaliplatin (n = 63) | mOS 8.1 mo vs. 9.0 mo vs. 6.9 mo (p = 0.56); 1-year OS 29% vs. 33% vs. 22%; mPFS 4.2 mo vs. 5.7 mo vs. 3.9 mo (p = 0.67); 1-year PFS 8% vs. 14% vs. 8%; response 13% vs. 25% vs. 13% (p = 0.13) |
| Cunningham [59] | 2009 | UK | 533 | Gemcitabine + capecitabine (830 mg/m2 bid po 3/4 weeks) (n = 267) vs. gemcitabine (standard dose) (n = 266) | mOS 7.1 mo vs. 6.2 mo (p = 0.08); 1-year OS 24.3% vs. 22.0%; mPFS 5.3 mo vs. 3.8 mo (p = 0.004); 1-year PFS 13.9% vs. 8.4%; response 19.1% vs. 12.4% (p = 0.03) |
| Poplin (E6201) [60] | 2009 | USA | 824 | Gemcitabine (n = 275) vs. fixed dose rate gemcitabine (n = 277) vs. gemcitabine plus oxaliplatin (n = 272) | mOS 4.9 mo vs. 6.2 mo vs. 5.7 mo; 1-year OS 16% vs. 22% vs. 21%; 2-year OS 4% vs. 6% vs. 6%; mPFS 2.6 mo vs. 3.5 mo vs. 2.7 mo |
| Kulke (CALGB 89904) [61] | 2009 | USA | 245 | Gemcitabine plus cisplatin (n = 62) vs. fixed dose rate gemcitabine (n = 58) vs. gemcitabine plus docetaxel (n = 65) vs. gemcitabine plus irinotecan (n = 60) | mOS 6.7 mo vs. 6.4 mo vs. 6.4 mo vs. 7.1 mo; mTTP 4.5 mo vs. 3.3 mo vs. 4.1 mo vs. 4.0 mo; response 13% vs. 14% vs. 12% vs. 14% |
| Colucci (GIP-1) [62] | 2010 | Italy | 400 | Gemcitabine + cisplatin (n = 201) vs. gemcitabine (n = 199) | mOS 7.2 mo vs. 8.3 mo (p = 0.38); 1-year OS 30.7% vs. 34.0%; mPFS 3.8 mo vs. 3.9 mo (p = 0.80); 1-year PFS 14.5% vs. 12.8%; response 12.9% vs. 10.1% (p = 0.37); clinical benefit 15.1% vs. 23.0% (p = 0.057) |
| Dahan (FFCD 0301) [63] | 2010 | France | 202 | 5-FU/folinic acid/cisplatin followed by gemcitabine (n = 102) vs. gemcitabine followed by 5-FU/folinic acid/cisplatin (n = 100) | mOS 6.7 mo vs. 8.03 mo (p = 0.83); mPFS 3.4 mo vs. 3.5 mo (p = 0.67); response 15% vs. 19% |
| PRODIGE 4/ ACCORD 11 [64] | 2011 | France | 342 | FOLFIRINOX (n = 171) vs. gemcitabine (n = 171) | mOS 11.1 mo vs. 6.8 mo (P <0.001); 1-year OS 48.4% vs. 20.6%; mPFS 6.4 mo vs. 3.3 mo (p < 0.001); 1-year PFS 12.1% vs. 3.5%; response 31.6% vs. 9.4% (p < 0.001); 6-month degradation QoL 31% vs. 66% (p < 0.001) |
| Ozaka (JACCRO PC-01) [65] | 2012 | Japan | 112 | Gemcitabine plus S-1 (n = 53) vs. gemcitabine (n = 59) | mOS 13.7 mo vs. 8.0 mo (p = 0.035); 1-year OS 55.9% vs. 29.0%; mPFS 6.15 mo vs. 3.78 mo (p = 0.0007); response 28.3% vs. 6.8% (p = 0.005) |
| Nakai (GEMSAP) [66] | 2012 | Japan | 106 | Gemcitabine plus S-1 (n = 53) vs. gemcitabine (n = 53) | mOS 13.5 mo vs. 8.8 mo (p = 0.104); 1-year OS 52.8% vs. 30.2% (p = 0.031); mPFS 5.4 mo vs. 3.6 mo (p = 0.036); response 18.9% vs. 9.4% (p = 0.265) |
| Chao [67] | 2013 | Taiwan | 46 | Gemcitabine + ciaplatin (n = 21) vs. gemcitabine (n = 25) | mOS 7.9 mo vs. 7.7 mo (p = 0.752); 1-year OS 9.5% vs. 12%; mTTP 3.6 mo vs. 4.6 mo (p = 0.857); partial response 4.8% vs. 8% (p = 1); clinical benefit 29% vs. 36% (p = 0.592) |
| Von Hoff and Goldstein (MPACT) [68] | 2013 and 2015 | International 11 countries | 861 | Gemcitabine + nab-paclitaxel (n = 431) vs. gemcitabine (n = 430) | mOS 8.7 mo vs. 6.6 mo (p < 0.001); 1-year OS 35% vs. 22% (p < 0.001); 2-year OS 10% vs. 5%; 3-year OS 4% vs. 0%; mPFS 5.5 mo vs. 3.7 mo (p < 0.001); 1-year PFS 16% vs. 9%; response 23% vs. 7% (p < 0.001); mTTF 5.1 mo vs. 3.6 mo (p < 0.001) |
| Ueno and Okusaka (GEST) [69,70] | 2013 and 2017 | Japan and Taiwan | 834 | Gemcitabine plus S-1 (n = 275) vs. S-1 (n = 280) vs. gemcitabine (n = 277) | mOS 9.9 mo vs. 9.7 mo vs. 8.8 mo; 1-year OS 40.7% vs. 38.7% vs. 35.4%; 2-year OS 14.5% vs. 12.7% vs. 9.2%; mPFS 5.7 mo vs. 3.8 mo vs. 4.1 mo; 1-year PFS 20.3% vs. 7.2% vs. 9.1%; response 29.3% vs. 21.0% vs. 13.3% |
| Sudo [71] | 2014 | Japan | 101 | Gemcitabine plus S-1 (n = 51) vs. gemcitabine (n = 50) | mOS 8.6 mo vs. 8.6 mo (p = 0.714); mPFS 5.3 mo vs. 3.8 mo (p = 0.039); response 21.6% vs. 6% (p = 0.048) |
| Petrioli [72] | 2015 | Italy | 67 | Gemcitabine + capecitabine + oxaliplatin (n = 34) vs. gemcitabine (n = 33) | mOS 11.9 mo vs. 7.1 mo (p < 0.001); mPFS 6.8 mo vs. 3.7 mo (p < 0.001); 4-month control 79.4% vs. 45.4% (p = 0.08) |
| Wang [73] | 2015 | Taiwan | 88 | Gemcitabine plus erlotinib (n = 44) vs. gemcitabine (n = 44) | mOS 7.2 mo vs. 4.4 mo (p < 0.001); mPFS 3.8 mo vs. 2.4 mo (p < 0.001); control 64% vs. 25% (p < 0.001) |
| Lee [74] | 2017 | Korea | 214 | Gemcitabine + capecitabine (830 mg/m2 bid po 3/4 weeks) (n = 103) vs. gemcitabine (standard dose) (n = 101) | mOS 10.3 mo vs. 7.5 mo (p = 0.06); mPFS 6.2 mo vs. 5.3 mo (p = 0.08); response 43.7% vs. 17.6% (p = 0.001) |