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©2014 Baishideng Publishing Group Inc.
World J Gastroenterol. Oct 28, 2014; 20(40): 14733-14746
Published online Oct 28, 2014. doi: 10.3748/wjg.v20.i40.14733
Published online Oct 28, 2014. doi: 10.3748/wjg.v20.i40.14733
Table 1 Major adjuvant chemotherapy trials in pancreatic cancer
| Final analysis | Survival (95%CI) | Disease-free survival (DFS)(95%CI) | |||||||||||||
| Year published | Author/group | Treatment arms (n) | T3 | N+ | R0 | Median survival (mo) | 1-yr survival | 2-yr survival | 3-yr survival | 5-yr survival | Median DFS (mo) | 1-yr DFS | 2-yr DFS | 3-yr DFS | 5-yr DFS |
| 1993 | Bakkevold | 5-FU/doxorubicin/mitomycinc (30) | NA | NA | 100% | 23 | - | 70% | 27% | 4% | - | - | - | - | - |
| Surgery alone (31) | 11 (P = 0.02) | 45% | 30% | 8% (P = 0.1) | |||||||||||
| 2001 | ESPAC-1 (all patients) | 5-FU/folinic fcid +/- CRT (238) | NA | 53% | 82% | 19.7 (16.4-22.4) | - | - | - | - | - | - | - | - | - |
| No chemotherapy +/- CRT (235) | 14 (11.9-16.5) (HR = 0.66, 0.52-0.83, P = 0.0005) | ||||||||||||||
| ESPAC-1 (2 × 2 design only) | 5-FU/folinic fcid +/- CRT (146) | NA | NA | NA | 17.4 (13.5-21.8) | - | - | - | - | - | - | - | - | - | |
| No chemotherapy +/- CRT (139) | 15.9 (13.5-19.2) (HR = 0.82, 0.6-1.11, P = 0.19) | ||||||||||||||
| 2002 | Takada | 5-FU/mitomycin C (89) | NA | 85% | 58% | NA | - | - | - | 11.5% | - | - | - | - | 8.6% |
| Surgery alone (84) | 18% (log rank NS) | 7.8% (log rank P = 0.84) | |||||||||||||
| 2004 | ESPAC-1 (2 × 2 final analysis) | 5-FU/folinic fcid (147) | NA | 54% | 82% | 20.1 (16.5-22.7) | - | 40% | - | 21% | - | - | - | - | - |
| No chemotherapy +/- CRT (142) | 15.5 (13-17.7) (HR = 0.71, 0.55-0.92, P = 0.009) | 30% | 8% | ||||||||||||
| 2006 | JSAP (Kosuge) | Cisplatin/5-FU (45) | NA | 27% | 100% | 12.5 | - | - | - | 26.4% | - | - | - | - | - |
| Surgery alone (44) | 15.8 | 14.9% (P = 0.94) | |||||||||||||
| 2007 | CONKO-001 (Oettle) | Gemcitabine (179) | 22.1 (18.4-25.8) | 72.5% | 47.5% | 34% | 22.5% | 13.4 (11.4-15.3) | 58% | 30.5% | 23.5% | 16.5% | |||
| Surgery alone (175) | 86 | 72% | 83% | 20.2 (17-23.4) (P = 0.06) | 72.5% | 42% | 20.5% | 20.5% | 6.9 (6.1-7.8) (P < 0.001) | 31% | 14.5% | 7.5% | 5.5% | ||
| 2008 | CONKO-001 Final (Neuhaus) | Gemcitabine (179) | 22.8 | - | - | 36.5 | 21 | 13.4 | - | - | 23.5 | 16.0 | |||
| Surgery alone (175) | 20.2 (P = 0.005) | 19.5% | 9% | 6.9 (P < 0.001) | 8.5% | 6.5% | |||||||||
| 2009 | JSAP-2 (Ueno) | Gemcitabine +/- RT (58) | 86% | 69% | 84% | 22.3 (16.1-30.7) | 77.6% | 48.3% | - | 23.9% | 11.4 (8-14.5) | 49% | 27.2% | - | - |
| Surgery alone +/- RT (60) | 18.4 (15.1-25.3) (HR = 0.77, 0.51-1.14, P = 0.19) | 75% | 40% | 10.6% | 5 (3.7-8.9) (HR = 0.6, 0.4-0.89, P = 0.01) | 26.7% | 16.7% | ||||||||
| 2009 | Collated data ESPAC-1, ESPAC-1 plus, ESPAC-3(v1) | 5-FU/folinic fcid (233) | NA | 55% | 75% | 23.2 (20.1-26.5) | 77% | 49% | - | 24% | - | - | - | - | - |
| Surgery alone (225) | 16.8 (14.3-19.2) (HR = 0.7, 0.55-0.88, P = 0.003) | 63% | 37% | 14% | |||||||||||
| 2010 | ESPAC-3(v2) | 5-FU/folinic fcid (551) | NA | 72% | 65% | 23 (21.1-25) | 78.5% (75%-82%) | 48.1% (43.8%-52.4%) | - | - | 14.1 (12.5-15.3) | 56.1% (51.8%-60.3%) | 30.7% (26.7%-34.6%) | - | - |
| Gemcitabine (537) | 23.6 (21.4-26.4) (HR = 0.94, 0.81-1.08, P = 0.39) | 80.1% (76.7%-83.6%) | 49.1% (44.8-53.4%) | 14.3 (13.5-15.6) | 61.3% (57.1%-65.5%) | 29.6% (25.6%-33.5%) | |||||||||
| 2013 | JASPAC-01 | S-1 (187) | 87% | 63% | 87% | 46.3 | - | 70% | - | - | 23.2 | - | 49% | - | - |
| Gemcitabine (191) | 25.5 (P < 0.0001) | 53% (HR = 0.56, 0.42-0.74, P < 0.0001) | 11.2 (log rank P < 0.0001) | 29% (HR = 0.56, 0.43-0.71, log rank P < 0.0001) | |||||||||||
Table 2 Meta-analyses of adjuvant chemotherapy in pancreatic cancer
| Survival (95%CI) | |||||
| Year published | Author | Arm (n) | Median survival (mo) | 2-yr survival | 5-yr survival |
| 2005 | Stocken et al[20] | CT (348) | 19 (16.4-21.1) | 38% | 19% |
| No CT (338) | 13.5 (12.2-15.8) | 28% | 12% | ||
| 2007 | Boeck et al[24] | CT (482) | 3 mo (0.3-5.7) survival benefit | - | 3.1% (-4.6%-10.8%) survival benefit |
| No CT (469) | with CT vs no CT (P = 0.03) | with CT vs no CT (P > 0.05) | |||
| 2008 | Butturini et al[25] | R0 resections | |||
| CT (236) | 20.8 (17.7-23.2) | 42% (35%-48%) | 22% (17%-28%) | ||
| No CT (222) | 13.8 (12.2-16.4) | 27% (21%-33%) | 10% (5%-14%) | ||
| R1 resections | |||||
| CT (109) | 15 (11.7-18.1) | 29% (20%-38%) | 14% (7%-21%) | ||
| No CT (114) | 13.2 (10.5-17.6) | 31% (22%-40%) | 17% (10%-24%) | ||
| 2013 | Liao et al[26] | Hazard ratio for death (95%CI) | |||
| Flurouracil (876) | 0.62 (0.42-0.88) | ||||
| Observation (670) | |||||
| Gemcitabine (774) | 0.68 (0.44-1.07) | ||||
| Observation (670) | |||||
| Gemcitabine (774) | 1.1 (0.70-1.86) | ||||
| Flurouracil (876) | |||||
Table 3 Major adjuvant chemoradiotherapy trials in pancreatic cancer
| Final analysis | Survival (95%CI) | Disease-free survival (DFS) (95%CI) | |||||||||
| Year published | Author/group | Treatment arms (n) | T3 | N+ | R0 | Median survival (mo) | 2-yr survival | 3-yr survival | 5-yr survival | Median DFS (mo) | 2-yr DFS |
| 1985 | GITSG | CRT (21) | 37 | 28 | 100 | 21 | 43% (0.25%-0.63%) | - | - | - | - |
| Surgery alone (22) | 10.9 | 18% (0.08%-0.36%) | |||||||||
| 1999 | EORTC | 5-FU/RT (104) | 21 | 46 | 77 | 24.5 | 51% (41%-61%) | - | 28% (17%-39%) | 17.4 | 38% (28%-48%) |
| Surgery alone (103) | 19 (log rank P = 0.208) | 41% (31%-51%) | 22% (12%-32%) | 16 (P = 0.643) | 37% (27%-47%) (P = 0.643) | ||||||
| 5-FU/RT (60) | 0 | 51 | NA | 17.1 | 37% (24%-50%) | - | 20% (5%-35%) | - | - | ||
| Surgery alone (54) | 12.6 (log rank P = 0.099) | 23% (11%-35%) | 10% (0%-20%) | ||||||||
| 2001 | ESPAC-1 (all patients) | CRT +/- 5-FU/folinic acid (175) | NA | 56 | 82 | 15.5 (13.5-17.4) | - | - | - | - | - |
| No CRT +/- 5-FU/folinic acid (178) | 16.1 (13.1-20.1) (HR = 1.18, 0.9-1.55, P = 0.24) | ||||||||||
| ESPAC-1 (2 × 2 design only) | CRT +/- 5-FU/folinic acid (142) | NA | NA | NA | 15.8 (13.5-19.4) | - | - | - | - | - | |
| No CRT +/- 5-FU/folinic acid (143) | 17.8 (14-23.6) (HR = 1.3, 0.96-1.77, P = 0.09) | ||||||||||
| 2004 | ESPAC-1 (2 × 2 final analysis) | CRT +/- 5-FU/folinic acid (145) | NA | 53 | 82 | 15.9 (13.7-19.9) | 29% | - | 10% | - | - |
| No CRT +/- 5-FU/folinic acid (144) | 17.9 (14.8-23.6) (HR = 1.28, 0.99-1.66, P = 0.05) | 41% | 20% | ||||||||
| ESPAC-1 (Individual Treatment Groups) | 5-FU/folinic acid (75) | 21.6 (13.5-27.3) | 29% | ||||||||
| CRT + 5-FU/folinic acid (72) | 19.9 (14.2-22.5) | - | - | 13% | - | - | |||||
| Observation (69) | 16.9 (12.3-24.8) | 11% | |||||||||
| CRT (73) | 13.9 (12.2-17.3) | 7% | |||||||||
| 2006 | RTOG 97-04 | CRT + 5-FU (230) | 75 | 66 | 66 | No significant difference | - | - | - | - | - |
| CRT + gemcitabine (221) | |||||||||||
| CRT + 5-FU (201) | NA | NA | NA | 16.9 | - | 22% | - | - | - | ||
| CRT + gemcitabine (187) | 20.5 (HR = 0.82, 0.65-1.03, P = 0.09) | 31% | |||||||||
| 2011 | RTOG 97-04 (5-yr analysis) | CRT + 5-FU (230) | 75 | 66 | 66 | No significant difference | 35% | 23% | 19% | n/s | - |
| CRT + gemcitabine (221) | HR = 0.933, 0.76-1.145, P = 0.51 | 40% | 27% | 19% | |||||||
| CRT + 5-FU (201) | NA | NA | NA | 17.1 | 34% | 21% | 18% (13%-24%) | - | - | ||
| CRT + gemcitabine (187) | 20.5 | 42% | 28% | 22% | |||||||
| 2012 | CapRI (Schmidt) | 5-FU/cisplatin/interferon α-2b → RT → 5-FU (53) | 97 | 79 | 61 | 32.1 (22.8-42.2) | - | - | - | 15.2 (10.3-24.8) | - |
| 5-FU/folinic acid (57) | 28.5 (19.5-38.6) (HR = 1.2, 0.49-2.95, P = 0.49) | 11.5 (9.8-17.6) (P = 0.61) | |||||||||
Table 4 Meta-analyses of adjuvant chemoradiotherapy in pancreatic cancer
| Survival (95%CI) | |||||
| Year published | Author | Arm (n) | Median survival (mo) | 2-yr survival | 5-year survival |
| 2005 | Stocken et al[20] | CRT | 15.8 (13.9-18.1) | 30% | 12% |
| No CRT | 15.2 (13.1-18.2) | 34% | 17% | ||
| 2008 | Butturini et al[25] | R0 Resections | |||
| CRT (188) | 15.9 (14-18.5) | 30% (23%-36%) | 10% (5%-15%) | ||
| No CRT (183) | 15.8 (13.4-20.1) | 38% (31%-45%) | 20% (13%-26%) | ||
| R1 Resections | |||||
| CRT (53) | 14.7 (11.5-20.5) | 30% (17%-42%) | 18% (7%-29%) | ||
| No CRT (53) | 11.2 (9.4-16.7) | 19% (8%-31%) | 8% (0%-16%) | ||
| 2013 | Liao et al[26] | Hazard ratio for death (95%CI) | |||
| Chemoradiation (169) | 0.91 (0.55-1.46) | ||||
| Observation (670) | |||||
| Chemoradiation + 5-FU (323) | 0.87 (0.27-2.69) | ||||
| 5-FU (876) | |||||
| Chemoradiation + 5-FU (323) | 0.59 (0.19-1.74) | ||||
| Chemoradiation (169) | |||||
| Chemoradiation + gemcitabine (221) | 0.82 (0.4-1.71) | ||||
| Chemoradiation + 5-FU (323) | |||||
Table 5 Current phase III trials investigating adjuvant therapy in pancreatic cancer
| Trial number | Co-ordinating country | First enrolment | Target sample size (n) | Adjuvant treatment arms | Primary outcome | Secondary outcomes (clinical only) |
| ISRCTN96397434 | United Kingdom | 2008 | 1396 | (I) Gemcitabine | OS | Toxicity |
| (ESPAC-4) | (II) Gemcitabine plus capecitabine | Quality of life | ||||
| OS at 2 and 5 yr | ||||||
| DFS at 5 yr | ||||||
| DRKS00000247 | Germany | 2008 | 436 | (I) Gemcitabine | DFS | OS |
| (CONKO-005) | (II) Gemcitabine plus erlotinib | Toxicity | ||||
| NCT01013649 | United States | 2009 | 950 | (I) Gemcitabine | OS | DFS |
| (RTOG 0848) | (II) Gemcitabine plus erlotinib | Toxicity | ||||
| If DFS at end of treatment (I) or (II), further randomisation to: | Correlation between baseline fatigue and survival | |||||
| (III) A further course of (I) or (II) as previously received plus Capcitabine CRT | ||||||
| (IV) A further course of (I) or (II) as previously received plus 5-FU CRT | ||||||
| NCT01072981 | United States | 2010 | 722 | Gemcitabine +/- 5-FU CRT +/- HyperAcute®-Pancreas (algenpantucel-L) immunotherapy | OS | |
| NCT01526135 | France/Canada | 2012 | 490 | (I) Gemcitabine | DFS at 3 yr | OS at 3 yr |
| (II) mFolfirinox (5-FU, folinic acid, irinotecan, oxaliplatin) | ||||||
| NCT01077427 | Germany | 2012 | 336 | (I) Gemcitabine | DFS | OS |
| (II) Gemcitabine plus cisplatin plus regional hyperthermia | ||||||
| NCT01964430 | United States | Not yet active | - | (I) Gemcitaine | DFS/OS | |
| (II) Gemcitabine plus nab-paclitaxel |
- Citation: Jones OP, Melling JD, Ghaneh P. Adjuvant therapy in pancreatic cancer. World J Gastroenterol 2014; 20(40): 14733-14746
- URL: https://www.wjgnet.com/1007-9327/full/v20/i40/14733.htm
- DOI: https://dx.doi.org/10.3748/wjg.v20.i40.14733