Topic Highlight
Copyright ©The Author(s) 2015.
World J Gastroenterol. Nov 7, 2015; 21(41): 11621-11635
Published online Nov 7, 2015. doi: 10.3748/wjg.v21.i41.11621
Table 1 Phase II studies on second-line therapy (Monotherapy) in metastatic gastric cancer
II line agentTotal/eval ptsPerformance status, nDoses(mg/m2)TreatmentORRMedianTTP (mo)MedianPFS(mo)MedianOS (mo)Toxicity,grade3-4 (%)Ref.
Irinotecan37/35ECOG 0/1 - 3/34Iri - 125 d1 weekly × 4 wk, q4220.0%2.6NR5.2A/L/N/T/N-E/D/FN/I - 56.8/45.9/67.6/8.1/ 18.9/18.9/16.2/8.1Chun et al[19], 2004
Irinotecan39/30ECOG 0/1/2 - 18/10/2Iri - 100 d1,d8,d15 q2815.3%2.9NR8.8A/N/Leu/Ano/D/F/- 13/30/17/23/17/13Mochizuki et al[20], 2013
Paclitaxel36/36ECOG 0/1/2 - 7/20/9Ptx - 225 d1 q2122.2%5.0NR8.0L/T - 17/17Cascinu et al[21], 1998
Paclitaxel38/25ECOG 0/1/2 - 12/15/11Ptx - 80 d1, 8, 15 q2824.0%2.1NR5.0L/N/T/Nau/Ano/D/ Neu - 29/32/8/3/3/3/6Hironaka et al[22], 2006
Paclitaxel45/44ECOG 0/1/2 - 26/13/6Ptx - 80 d1, 8, 15 q2816.0%NR2.67.8A/N/L/D/N-E/As/Neu - 11/16/18/2/4/11/2Kodera et al[23], 2007
Docetaxel30/29KPS Median 70 (R 60-100%)Dtx - 100 d1 q2117.0%NRNR6.0A/L/N - 7/7/18Giuliani et al[24], 2003
Docetaxel154/86ECOG 0-1/2 - 130/24Dtx - 75 d1 q2114.0%2.6NR7.2A/N/FN/As - 10.5/12.5/9.9/13.61Jo et al[25], 2007
Docetaxel49/49ECOG 0/1/2 - 9/36/4Dtx - 75 d1 q2116.5%2.5NR8.3A/L/N/FN/B/As/D/Neu - 5.4/4.8/5.4/5.4/1.2/ 10.8/2.4/8.4Lee et al[26], 2008
Nab-Paclitaxel56/54ECOG 0/1 - 33/23Nab-Ptx 250 d1 q2127.8%NR2.99.2A/L/N/Ly/Neu - 7.3/20/49.1/10.9/23.6Sasaki et al[27], 2014
Pemetrexed34/30ECOG 0/1/2 - 7/20/7Pem - 500 d1 q 2163.6%NR2.36.4A/N/T/As - 2.9/2.9/2.9/5.8Zhang et al[28], 2015
Sunitinib78/69ECOG 0/1 - 26/52Sun - 50 mg/d × 4 wk, q422.6%2.32.36.8A/L/N/T/E/D/HFS/S - 16.7/11.5/29.4/34.6/ 3.8/2.6/6.4/1.3Bang et al[29], 2010
Everolimus54/53ECOG 0/1 - 32/21Ev - 10 mg/d d1-280%NR2.710.1P (gr 1-2)/A/Ly/As/S/ Ano/HyG/HyP/HyN/ - 15.1, 9.4/7.5/5.7/ 5.7/ 5.7/3.8/3.8/9.6Doi et al[30], 2010
Table 2 Phase II studies on second-line therapy (combination therapy) in metastatic gastric cancer
StudyTotal /eval ptsPerformance Status, nII-line treatment,doses (mg/m2)TreatmentORRMedian TTP (mo)MedianPFS(mo)MedianOS(mo)Toxicity,grade3-4 (%)Ref.
Irinotecan/ FU40/38ECOG 0/1/2 - 5/21/12Iri/FA/FU - 180/125/400 bolus + 1200 inf over 22 h d1/d1/d1 q1429.0%NR3.76.4A/N/FN/I/N-E/D/As - 13/26/5/16/13/8/16Assersohn et al[31], 2004
Irinotecan/ FU64/57ECOG 0/1/2 - 3/58/3Iri/FU/FA - 150/100/1000 d1/d1/d1, 2 over 24 h q1421.0%2.5NR7.6N/T/D/E - 11/8/3/3Kim et al[32], 2005
Irinotecan/ FU51/48ECOG 0-1/2 - 35/16Iri/FA/FU - 180/200/400 bolus + 600 inf over 22 h d1/d1/d1 q1418.0%NR3.29.1A/N/FN/D/Nau/E - 14/17/1/6/6/41Seo et al[33], 2008
Irinotecan/ Cisplatin32/31ECOG 0/1/2 - 1/22/9Iri/P - 70/30 d1, 15/d1, 15 q2815.6%3.7NR6.1A/N/T/E/D/M/Ano - 2.6/6/4.3/1.7/1.7/3.4/5.2Baek et al[34], 2005
Irinotecan/ Cisplatin87/70ECOG 0/1/2 - 29/53/5Iri/P - 70/80 d1, 15/d1 q2828.6%4.3NR9.5A/L/N/FN/T/D/As/Nau - 28/34/40/10/8/6/5/21Takahari et al[35], 2010
Irinotecan/ Mitomycin C38/38KPS Median 80 (R 70-100%)Iri/MMC - 150/8 d1, 15/d1 q2832.0%4.0NR8.0A/L/N - 5/8/21Giuliani et al[36], 2005
Irinotecan/ Mitomycin C45ECOG 0/1 - 24/21Iri/MMC - 150/5 d1 q1429.0%NR4.110.1A/N/FN/D/I - 13/53/9/2/4Hamaguchi et al[37], 2011
Irinotecan/ Capecitabine48/46ECOG 0/1/2 - 10/32/6Iri/Cap - 100/1000 b.i.d d1, 8/d1-14 q2127.1%4.1NR7.6N/FN/E/D/HFS - 8.7/4.3/4.3/17.4/4.3Sun et al[38], 2009
Irinotecan/ Cetuximab63/54ECOG 0/1 - 28/35Iri/Cet - 180/500 d1 q1411.0%NR2.86.1N/FN/D/F - 11/2/6/5Schønnemann et al[39], 2012
Irinotecan vs29 vs 30ECOG 0/1 - 27/2 vs 27/3Iri 150 d1 q1417.2% vs 20.0%NR2.2 vs 35.8 vs 6.7A/n/Leu/FN/Ano/As/D - 0/20/28/0/10/10/3 vs 10/13/37/3/13/3/7Sym et al[40], 2013
Irinotecan/ mFOLFIRIIri/mFOLFIRI 150 d1 + LV20 d1, 5-FU 2000 over 48 h
Paclitaxel/ Doxifluridine52/25ECOG R 0-2Dox/Ptx - 600 mg/70 d1-21/d7, 14, 21 q2828.0%NRNR5.8L - 2Arai et al[41], 2007
Paclitaxel/ Doxifluridine33ECOG 0/1/2 - 21/14/0Dox/Ptx - 600 mg/70 d1-14/d1, 8 q2118.2%NR4.010.7A/L/N/D/FN/I/As/Neu - 17.1/11.4/22.9/2.9/ 2.9/2.9/2.9Takiuchi et al[42], 2008
Paclitaxel/ Carboplatin50/47ECOG 0-1/2 - 25/22Ptx/Carbo - 175/AUC 5 d1/d1 q2127.7%NRNROS in PR/SD - 10.0/6.0N/T - 8.5/4.2Stathopoulos et al[43], 2002
Paclitaxel/ Cisplatin32/30ECOG 0-1/2 - 21/11Ptx/P - 145/60 d1 q2125.0%2.9NR9.1N/E/Neu - 3/9/6Lee et al[44], 2007
Paclitaxel/ Capecitabine26/26ECOG 0/1/2 - 7/11/8Ptx/Cap - 175/825 b.i.d d1/d1-14 q2134.6%4.5NR7.5A/N/T/HFS/Neu/Ar/E - 3.8/11.5/3.8/11.5/ 11.5/7.5/3.8Baize et al[45], 2009
Paclitaxel/ Capecitabine36/35KPS Median 80 (R 60-100%)Ptx/Cap - 80/1000 b.i.d d1, d8/d1-14 q2128.5%NR5.011.1N/N-E/HFS - 11.1/5.6/5.6Zhang et al[46], 2013
Paclitaxel/ S-130ECOG 0-1/2 -23/7Ptx/S-1 - 120 d1 q14 /80, 100, 120 mg/d, if BSA < 1.25 m2, 1.26 m2-1.49 m2, ≥ 1.50 m2 b.i.d. d1-7 q1433.3%NR3.67.2A/Neu/T/Ano/Neu/D/F - 73.4/63.4/16.6/20/36.6/13.3/20Zheng et al[47], 2014
Docetaxel/ Cisplatin43/41ECOG 0/1/2 - 1/33/9Dtx/P - 60/60 d1/d1 q2117.1%NR2.25.8N/N-E/Neu/Neph - 29.3/12.2/4.9/2.3Park et al[48], 2004
Docetaxel/ Cisplatin30/30KPS 50-70/ 80-100% - 14/16Dtx/P - 60/60 d1/d1 q2126.7%4.5NR5.6A/L/N/Nau - 3/27/27/3Kunisaki et al[49], 2005
Docetaxel/ Cisplatin32/32ECOG 0/1/2 - 8/16/8Dtx/P 70/70 d1/d1 q2116.0%5.0NR6.0N/FN/T/D - 59/12/12/6Polyzos et al[50], 2006
Docetaxel/ Oxaliplatin38/37ECOG 0/1/2 - 19/12/7Dtx/Ox - 75/80 d1/d2 q2110.5%4.0NR8.1N/As/Nau/Neu - 26.3/15.7/15.7/3Barone et al[51], 2007
Docetaxel/ Oxaliplatin48/46ECOG 0/1/2 - 11/29/8Dtx/Ox - 60/130 d1 q2122.9%4.4NR7.2L/N/FN/T/N-E/D/Neu - 17.4/26/7/4.3/28.3/ 15/6.5Zhong et al[52], 2008
Docetaxel/ Epirubicin50/45ECOG 0/1/2 - 12/16/22Dtx/Epi - 75/60 d1/d1 q2115.5%2.4NR5.0N/FN/T/N-E/S/D/Neu - 68/48/46/2/8/4/2Nguyen et al[53], 2006
Docetaxel/ Capecitabine28/25ECOG 0/1/2 - 2/19/7Dtx/Cap - 60/1000 b.i.d d1/d1-14 q2129.0%4.0NR6.0A/N/As/D/HFS - 7/36/7/11/7Rosati et al[54], 2007
Docetaxel/ Etoposide32/32ECOG 0/1/2 - 6/20/6Dtx/Eto - 75/50 d1/d1-5 q219.4%NR3.06.0N/FN/T/N-E/D/M - 29/19/3/15.6/9.4/6.2Yildiz et al[55], 2010
Docetaxel/ Cetuximab38/35ECOG 0/1/2 - 15/21/2Dtx/Cet - 30 d1, d15 q21/400 d1, then 250 d1 q76.0%NR2.15.4I/FN/Ano/D/F - 11/3/16/11/29Tebbutt et al[56], 2013
Mitomycin/ S143/33ECOG 0/1/2 - 13/21/9MMC/S-1 - 7/40 b.i.d d1/d1-28 q4221.0%NR3.48.0A/N/T/D/N-E/As/S - 7/5/5/10/7/12/10Park et al[57], 2008
Mitomycin/ Capecitabine39ECOG 0/1/2/UNK - 6/25/5/3MMC/Cap - 10/1000 bid d1/d1-d14 q2110.3%NR2.85.6Leu/T/D/F/HFS/Neu - 5.4/10.8/5.4/8.1/5.4/8.1Miranda et al[58], 2014
Methotrexate/ FU56/55ECOG 0/1/2/3 - 12/30/12/2Mtx/FU/FA - 100 bolus/600 bolus (3 h after MTX)/10, every 6 h for 6 doses (24 h after MTX) q79.0%NRNR7.8A/L/N/T/N-E/D/S - 9.1/5.5/6.7/1.8/3.6/ 3.6/1.8Hamaguchi et al[59], 2008
Cisplatin/ FU58/53ECOG 0-1/2 - 20/33P/FU - 20/1000 over 20 h inf d1-5/d1-5 q2811.3%1.8NR4.6A/N/T/N-E/D/M/Neu - 8/9/9/11/4/6/1Sencan et al[60], 2008
Oxaliplatin/ Sorafenib40ECOG 0/1/2 - 14/23/2Ox/Sor - 130 d1 q21/400 mg b.i.d daily2.8%NR3.06.5N/T/As/D/Neu - 9.8/7.3/18/4.9/4.9Martin-Richard et al[61], 2013
Table 3 Phase III studies on second-line therapy in metastatic gastric cancer
Ref.II-line treatment (mg/m2)Total ptsPerformance Status, (ECOG/WHO) (%)Median ORR (%)MedianPFS(mo)MedianOS(mo)Hazard ratioToxicity,grade3-4 (%)
Thuss-Patience et al[62], 2011Iri 250 cycle 1; 350 subsequent cycles21/190-1/2 - 81/1902.54.00.48, P = 0.012D/FN/L/A - 26/16/21/11
BSC190-1/2 - 74/26NRNR2.4NR
Kang et al[63], 2012Dtx 60 d1 q3w;1330/1 - 54/4613.0NR5.30.657, P = 0.007Doc: N/A/F/Ano/D/S - 15/30/26/6/3/3
Iri 150 d1 q2wIri: N/A/F/Ano/D/S - 18/32/10/5/8/5
BSC690/1 - 52/48NRNR3.8N/A/F/D/S - 2/23/27/10/5/2
Hironaka et al[64], 2013Iri 150 d1/d15 q4w1120-1/2 - 96.4/3.613.612.318.41.13, P = 0.38L/N/A/FN/Ano/Neu/D/AST/Na - 19.1/39.1/30/9.1/17.3/0/4.5/8.2/15.5
Ptx 80 d1/d8/d15 q4w1110-1/2 - 96.3/3.720.913.619.5L/N/A/FN/Ano/Neu/D/AST/Na - 20.4/28.7/21.3/2.8/7.4/7.4/0.9/3.7/3.7
Ford et al[65], 2014Doc 75 d1 q3w840/1/2 - 28/55/177.029% (at 24 wk)5.20.67, P = 0.01N/A/FN/I/H/P/Neu - 15/6/7/15/1/11/4
BSC840/1/2 - 28/60/14NRNR3.6N/A/FN/I/H/P/Neu - 0/5/0/3/6/20/4
Higuchi et al[66], 2014Iri 60 d1 q2w;640/1 - 69/3122.013.810.711.00, P = 0.982N/A/FN/T/D/Ano/F - 13/16/0/0/2/6/3
Cis 30 d1 q2w
Iri 150 d1 q4w660/1 - 68/3216.012.810.11N/A/FN/T/D/Ano/F - 36/18/5/2/6/11/6
Nishikawa et al[67], 2015Iri 60 d1 q2w;840/1 - 81/1916.914.6113.910.834, P = 0.288N/A/T/D/Ano/F - 35/16/1/0/6/9
P 30 d1 q2w
Iri 150 d1 q4w840/1 - 75/2515.414.1112.71N/A/T/D/Ano/F - 28/4/0/3/9/4
Fuchs et al[69], 2014Ram 8 mg/kg d1 q2w2380/1/2 - 28/72/03.412.15.20.776, P = 0.047A/F/AbP/Dys/Dyn/Hyt/B/Prot/VTE - 6/6/6/2/2/8/3/< 1/1
BSC
Placebo1170/1/2 - 26/73/03.011.33.8A/F/AbP/Dys/Dyn/Hyt/B/Prot/VTE - 8/10/3/4/6/3/3//< 1
BSC
Wilke et al[70], 2014Ram 8 mg/kg d1,15 q4w3300/1 - 35/65274.49.60.807, P = 0.017N/A/Leu/T/F/Neu/D/H/Hyt/Prot/HepF/VTE - 41/9/18/2/8/4/4/15/1/4/2
Ptx 80 d1/d8/d15 q4w
Placebo3350/1 - 43/57162.97.4N/A/Leu/T/F/Neu/D/H/Hyt/Prot/HepF/VTE - 19/9/6/2/5/5/1/4/3/0/3/2
Ptx 80 d1/d8/d15 q4w
Satoh et al[76], 2014Lap 1500 mg once daily1320/1 - 45/55275.5112.210.84, P = 0.2(experienced in > 10% of pts) N/A/Lym/F/Neu/D - 57/11/29/5/< 1/18
Ptx 80 d1,d8,d15 q4w
Placebo1290/1 - 37/6394.4110.51(experienced in > 10% of pts) N/A/Lym/F/Neu/D - 31/6/2/< 1/0/2
Ptx 80 d1,d8,d15 q4w
Dutton et al[77], 2014Gef 500 mg/d daily2240/1/2 - 25/52/2224 (DC)1.573.7310.90, P = 0.293D/F/Sk/Rep/I/Hem/Vas/Met - 6/10/20/12/3/7/7/6
Placebo2250/1/2 - 25/55/2016 (DC)1.173.671D/F/Sk/Rep/I/Hem/Vas/Met - 1/5/< 1/12/4/4/5/7