Table 1.
Patient characteristics, side effects and survival in different gastric cancer trials
| Clinical Trial | INT-0116 | MAGIC | ACTS-GC | CLASSIC | ARTIST | Zhu 2012 |
|---|---|---|---|---|---|---|
|
Number of patients |
556 |
503 |
1059 |
1035 |
458 |
380 |
|
Tumor location |
Stomach: 80% GEJ: 20% |
Stomach: 74%; esophagus: 14.5%; GEJ: 11.5% |
100% stomach |
97.7% stomach; 2.3% GEJ |
100% stomach |
80.5% stomach; 19.5% GEJ |
|
Treatment in CT/CRT arm |
Resection (D2: 10%), adjuvant FU/FA with 45/1.8Gy* |
Perioperative 6 cycles of FU/epirubicin/cisplatin; D2 resection in 42.5%† |
D2 (94.7%) or D3 (5.3%) surgery; adjuvant S-1 |
D2 surgery; Adjuvant capecitabine and oxaliplatin |
D2 resection, adjuvant XP, 45/1.8Gy/capecitabine; 2 cycles XP§ |
D2 resection; 1 cycle adjuvant FU/FA; 45/1.8Gy IMRT/FU/FA; followed by 2 cycles FU/FA |
|
Treatment in control arm‡ |
Resection alone (D2: 10%)* |
D2 resection in 40.4% of cases† |
D2 (93.8%) or D3 (6%) resection (D1 in 0.2%) |
D2 surgery |
D2 surgery; adjuvant XP |
D2 resection; adjuvant FU/FA only |
|
AJCC/UICC stage (or TNM) in CT/CRT arm |
T1-2: 31%; T3-4: 69%; N0: 16%; N+: 84%‡‡ |
T1-2: 51.7%; T3-4: 48.3%; N0: 31.1%; N+: 68.9%‡‡ |
II: 44.6%; IIIA: 38.2%; IIIB: 17.0%; IV: 0.2% |
IB: <1%; II: 49%; IIIA: 37%; IIIB: 14%; IV: 0% |
IB: 21.3%; II: 36.5%; IIIA: 23%; IIIB: 7.8% IV: 11.3% |
IB: 10.8%; II: 19.4%; III: 55.4%; IV: 14.5% |
|
AJCC/UICC stage (or TNM) in control‡arm |
T1-2: 31%; T3-4: 68%; N0: 14%; N+: 85%‡‡ |
T1-2: 36.8%; T3-4: 63.2%; N0: 26.9%; N+: 73.1%‡‡ |
II: 44.9%; IIIA: 39.1%; IIIB: 16.0%; IV: 0% |
I: 0%; II: 51%; IIIA 36%; IIIB 13%; IV: <1% |
IB: 21.9%; II: 37.7%; IIIA: 21.1%; IIIB: 7.5%; IV: 11.8% |
IB: 9.1%; II: 18.2%; III: 58.2%; IV: 14.5% |
|
OS in CT/CRT arm# |
3-yr: 50% (p=0.005) 5-yr: ~42% |
3-yr: ~42% 5-yr: 36.3% (p=0.008) |
3-yr: 80.1% (p=0.003) 5-yr: 71.7% |
3-yr: 83% (p=0.0493) |
Unspecified |
5-yr: 48.4% (p=0.122) 3-yr: ~62% |
|
OS in control‡arm# |
3-yr: 41% (p=0.005) |
3-yr: ~31% 5-yr: 23.0% (p=0.008) |
3-year: 70.1% (p=0.003) 5-yr: 61.1% |
3-yr: 78% (p=0.0493) |
Unspecified |
5-yr: 41.8% (p=0.122) 3-yr: ~53% |
|
DFS in CT/CRT arm# |
3-yr: 48% (p<0.001) 5-yr: ~40% |
3-yr: ~40% (p<0.001) |
3-yr: 72.2% (p<0.001) 5-yr: 65.4% |
3-yr: 74% (p<0.0001) |
3-year: 78.2% (p=0.0862)§§ |
3-yr: ~59% 5-yr: 45.2% (p=0.029) |
|
DFS in control‡arm# |
3-yr: 31% (p<0.001) |
3-yr: ~24% (p<0.001) |
3-yr: 59.6% (p<0.001) 5-year: 53.1% |
3-yr: 59% (p<0.0001) |
3-year: 74.2% (p=0.0862)§§ |
3-yr: ~47% 5-yr: 35.8% (p=0.029) |
|
Grade 3–4 hematologic events in CRT/CT arm |
Hematologic events: 54%; most common: leukopenia; no further details specified |
Leukopenia: 11.5% Neutropenia: 27.8% Lymphopenia: 19.9% Thrombopenia: 3% |
Leukopenia: 1.2% Neutropenia and Lymphopenia unspecified Thrombopenia: 0.2% |
Leukopenia: unspecified Neutropenia: 22% Lymphopenia: unspecified Thrombopenia: 8% |
Leukopenia: unspecified Neutropenia: 48.5% Lymphopenia: unspecified Thrombopenia: 0.9% |
Leukopenia: 7.5% Neutropenia and Lymphopenia unspecified Thrombopenia: 0% |
|
Grade 3–4 hematologic events in control‡arm |
Unspecified |
Unspecified |
Leukopenia: 0.4% Thrombopenia: 0.4% |
Leukopenia: unspecified Neutropenia: <1% Thrombopenia: 0% |
Leukopenia: unspecified Neutropenia: 40.7% Thrombopenia: 0% |
Leukopenia: 7.3% Neutropenia: unspecified Thrombopenia: 0% |
|
Most common grade 3–4 non-hematologic events in CRT/CT arm |
Gastrointestinal: 33% Influenza-like: 9% Infection: 6% |
Nausea: 12.3% Vomiting: 10.1% Stomatitis: 4.3% |
Anorexia: 6% Nausea: 3.7% Diarrhea: 3.1% |
Nausea: 8% Vomiting: 7% Decreased appetite: 5% |
Nausea: 12.3% Vomiting: 3.1% Hand-foot syndrome: 3.1% |
Nausea: 2.7% Vomiting: 1.6% Diarrhea: 1.6% |
| Most common grade 3–4 non-hematologic events in control‡arm | Unspecified | Unspecified | Anorexia: 2.1% Vomiting: 1.9% Nausea: 1.1% | Each single event <1% | Nausea: 12.4% Vomiting: 3.5% Hand-foot syndrome: 2.2% | No grade 3–4 non-hematologic toxicities in CT group |
* D2 resection in 10% of patients, D1 in 36%, and D0 in 54% of patients; curative resection was inclusion criterion; radiotherapy was conventional 2d therapy.
† Patients that did not receive D2 resection were D1-, D0 or non-curatively resected; R0 resection was achieved in 69.3% of patients in CT arm and in 66.4% in surgery only arm.
§ XP: capecitabine and cisplatin; in the CRT group, 2 cycles XP were administered, followed by CRT: 45Gy in 1.8Gy fractions, concomitant capecitabine, followed by another 2 cycles of XP.
§§ In a subgroup analysis of 396 N+ patients, there was a significant prolongation in DFS in the adjuvant CRT arm as compared to the adjuvant CT arm: 3-year DFS 77.5% vs. 72.3%; p=0.0365.
‡ In INT-0116, MAGIC, ACTS-GC, and CLASSIC control arm was surgery only; in ARTIST trial and Zhu 2012 trial, adjuvant CT without radiotherapy was considered as control arm and adjuvant CRT as CT/CRT arm.
‡‡ Patient populations between INT-0116 and MAGIC should be compared in control groups only; the treatment group in MAGIC refers to patients who received CT before surgery and were therefore staged down.
#Survival data marked with “~” are estimates from the published survival curves.
Patient characteristics, outcome and side effects in different gastric cancer trials are summarized. In the MAGIC trial, randomization was performed before surgery; patients in the other trials were randomized after curative surgery had been performed. The method of randomization after surgery in the INT-0116 trial and the low rate of curative resections in the MAGIC trial distort any direct comparison of results between these landmark trials. The ARTIST trial and the Chinese trial by Zhu et al. compare CT to CRT in an adjuvant setup of gastric cancer patients. In the ARTIST trial, an improved DFS by CRT as compared to CT was demonstrated in trend in the whole population; this observation was significant in the subgroup of N+ patients. Zhu et al. reported in a Chinese population a significantly improved DFS (by CRT vs. CT) in all patients, this inconsistency most probably being due to the more advanced patients in the Chinese trial. A direct comparison in terms of AJCC stage between ARTIST and the trial by Zhu et al. is not possible as in the ARTIST trial, patients were staged according to the 6th AJCC staging system; Zhu and coworkers reported patient classification according to the 7th AJCC staging system.