Evidence based radiation therapy for locally advanced resectable and unresectable gastric cancer

Table 1 Randomized trials for postoperative chemo-radiotherapy in resectable gastric cancer

Author, year published	Nr Pt	Treatment arms	Local control	Overall survival
Moertel et al[12], 1984	62	Arm 1 (23 patients): Observation only Arm 2 (39 patients): 5-FU (15 mg/kg by rapid intravenous injection × 3) plus radiation (3750 rad in 24 fractions)	The alive without recurrence distributions were significantly different for the two groups (P = 0.024) and favored treatment assignment.	The five year survival rate for patients randomized to treatment was 23%, and for those randomized to no treatment, 4% (P < 0.05).
Kim et al[15], 2005	990	Arm 1 (446 patients): no adjuvant treatment Arm 2 (544 patients): 400 mg/m2 of 5-FU plus 20 mg/m2 of LV for 5 d, followed by 4500 cGy of RT for 5 wk, with 5-FU and LV on the first 4 and the last 3 d of RT. Two additional cycles of the chemotherapy were given 4 wk after the completion of RT	The CRT was associated with increases in the median duration of relapse-free survival (75.6 mo vs 52.7 mo; hazard ratio for relapse, 0.80, P = 0.016).	Overall survival was significantly longer in the CRT arm: 95.3 mo vs 62.6 mo (hazard ratio for death of 0.80, P = 0.02)

Nr: Number; Pt: Patients; 5-FU: 5-fluorouracil; LV: Leucovorin; CRT: Chemo-radiotherapy.

Table 2 Phase II trials for preoperative chemo-radiotherapy in resectable gastric cancer

Author,year published	Nr Pt	Treatment schedule	PathCR rate	Quality of surgery
Ajani et al[16], 2006	49	Patients received two cycles of induction 5-FU, LV and CIS followed by concurrent CRT (infusional 5-FU and weekly paclitaxel). Resection was attempted 5 to 6 wk after CRT	27%	The R0 resection rate was 77%
Ajani et al[17], 2004	33	Patients received two cycles of induction 5-FU, LV and CIS followed by concurrent CRT (infusional 5-FU).	30%	The R0 resection rate was 70%
Ajani et al[18], 2005	41	Patients received two cycles of induction 5-FU, LV and CIS followed by concurrent CRT (infusional 5-FU and weekly paclitaxel).	25%	The R0 resection rate was 78%

Nr: Number; Pt: Patients; 5-FU: 5-fluorouracil; LV: Leucovorin; CIS: Cisplatin; CRT: Chemo-radiotherapy; PathCR: Pathologic complete response; R0: Microscopically negative surgical margins.

Table 3 Ongoing phase III trials for resectable gastric cancer

Study	Sponsor	Estimated Enrollment	Arms	Primary endpoint
Adjuvant chemotherapy or chemoradiotherapy in resectable gastric cancer (CRITICS)	Dutch colorectal cancer group	788	1 CRT(Experimental): cisplatin 20 mg/m2 (IV, q 1 w, 5 wk), capecitabine 575 mg/m2 (bid, oral, on radiotherapy days). Radiation therapy: 45 Gy in 25 fractions (5 d/wk).	Whether chemoradiotherapy after preoperative chemotherapy and adequate surgery leads to improved survival in comparison with postoperative chemotherapy.
			2 C (Active comparator): 3 courses q 3 w: epirubicin 50 mg/m2 (IV, day 1), cisplatin 60 mg/m2 (IV, day 1), capecitabine 1000 mg/m2 (bid, oral, day 1-14).
			All patients receive 3 cycles of the C in arm 2 before surgery.
Chemotherapy and radiation therapy after surgery in treating patients with stomach or esophageal cancer	Cancer and leukemia group B	824	1 (Active comparator): Patients receive leucovorin calcium IV and fluorouracil (5-FU) IV on days 1-5 of courses 1, 3 and 4. Courses repeat every 28 d. During course 2, patients undergo radiotherapy 5 d a week and receive 5-FU IV continuously for 5 wk. Patients rest for 28-35 d between course 2 and 3.	Compare overall survival in patients with resected gastric adenocarcinoma treated with epirubicin, cisplatin and infusional 5-FU vs 5-FU bolus and leucovorin calcium before and after 5-FU plus radiotherapy.
			2 (Experimental): Patients receive epirubicin IV over 3-15 min and cisplatin IV over 1 h on day 1 and 5-FU IV continuously on days 1-21 during course 1. Beginning 1 wk later, patients undergo radiotherapy 5 d a week and 5-FU IV continuously for 5 wk. Patients rest for 28-35 d before beginning course 2 of chemotherapy. Patients then receive epirubicin, cisplatin and 5-FU as in course 1. Treatment repeats every 21 d for 2 courses.

5-FU: 5-fluorouracil; LV: Leucovorin; CRT: Chemo-radiotherapy; C: Chemotherapy; q 1 w: Given every one week; bid: Given two times per day; q 3 w: Given every three weeks; IV: Intravenous.