Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy in gastric cancer

Table 3 Hyperthermic intraperitoneal chemotherapy in the treatment of established peritoneal carcinomatosis from gastric cancer

Ref.	Country	Type of study	No. of patients study arm control		Drug used for HIPEC, dose	Duration (min)	Complete cytoreduction	Morbidity	Mortality	Outcome
Fujimoto et al[66], 1990	Japan	Prospective	20 (surgery + HIPEC)	7 ( only surgery)	MMC 10 μg/mL	120	NA	NA	NA	6 mo survival: 94% vs 57%, P = 0.001
										2-yr: 45%
										Death due to Peritoneal recurrence: 10% vs 100%
Yonemura et al[91], 1991	Japan	Prospective	41	Nil	MMC 5 μg/mL	40-60		12%	0%	Median survival: 14.5 mo
					CDDP 30 μg/mL					3-yr: 28.5%
Yonemura et al[26], 1996	Japan	Prospective	83 (surgery + HIPEC)	Nil	MMC 30 mg	60	33.7%			5-yr survival (overall: 11%, CCR0/1: 17%, CCR2: 2%)
					CDDP 300 mg
					Etoposide 150 mg					Median survival CCR0: 13.9, CCR ≥ 1: 6.8 mo
Fujimoto et al[92], 1997	Japan	Prospective case-control	48 (surgery + HIPEC)	18 (only surgery)	MMC 10 μg/mL	120				1,3,5,8-yr survival (HIPEC vs control: 54% vs 11%, 42% vs 0%, 31% vs 0%, 25% vs 0%; P = 0.001)
										2, 4, 8-yr survival - P1, P2, P3 - 73%, 62%, 0%; 56%, 62%, 0%; 56%, 21%, 0% (P1 vs P3: P = 0.000524; P2 vs P3: P = 0.00329).
										Death due to peritoneal recurrence-HIPEC vs control 27% vs 94% (P = 7.077 × 100-7).
Glehen et al[94], 2004	France	Prospective	49 (CRS + HIPEC)	Nil	MMC 40-60 mg	90	10.2%	Overall - 27%	4%	Median survival (overall: 10.3 mo; CCR0/1 vs CCR2: 21.3 mo vs 6.6 mo, P < 0.001; Gilly Stage I/II PC vs stage III/IV PC: 19 mo vs 6.6 mo, P = 0.004)
								Extensive CRS - 47%
										5-yr survival (overall: 16%, CCR0/1: 29.4%, Gilly Stage I/II PC: 30%)
Hirose et al[75], 1999	Japan	Prospective case- control	17 (CRS +HIPEC)	20 (CRS alone)	MMC 20 mg	50	HIPEC vs control-	HIPEC vs control - 35.2 vs 20%	HIPEC vs control - 5.8% vs 0%	Median survival: HIPEC vs control: 11 mo vs 6 mo
					CDDP 100 mg					1-yr survival: HIPEC vs control: 44.4% vs 15.8%, P = 0.04
					Etoposide 100 mg		29.4% vs 15%
Hall et al[99], 2004	United States	Prospective case-control	34 (CRS +HIPEC)	40- no PC (only surgery)	MMC 40 mg	120	R0-21%	35%	0%	Median survival (CRS + HIPEC): Overall: 8 mo; R0/1 vs, R2: 11.2 mo vs 3.3 mo, P = 0.01
							R1-14%			2-yr survival - R0/1 vs, R2-45 vs 8%
Yonemura et al[95], 2005	Japan	Retrospective	42 (peritonectomy [P] + HIPEC)	65 (conventional surgery [C] + HIPEC)	MMC 30 mg	60	Overall 43.9%	Overall - 21.5%	Overall 2.8%	Median survival: Overall: 11 mo; CCR0: 15.5 mo; CCR ≥ 1: 7.9 mo (all patients);
					CDDP 300 mg		P + HIPEC 69% C + HIPEC 28%	P + HIPEC- 43%	P + HIPEC- 7%	CCR0: 19.2 mo; CCR ≥ 1: 7.8 mo (P + HIPEC patients)
					Etoposide 150 mg			C + HIPEC - 8%	C + HIPEC- 0%	5-yr survival: overall-6.7%; P + HIPEC-27%; CCR0: 13%, CCR ≥ 1%-2%
Scaringi et al[100], 2008	France	Retrospective	37 (26 with PC)	Nil	MMC 120 mg	60-90	30.7%	27% (all patients)	3.8%	Median survival:
					CDDP 200 mg/m2					CCR0 vs CCR2- 15 mo vs 3.9 mo, P = 0.007
										Gilly stage 1 and 2 vs 3 and 4: 15 mo vs 4 mo, P = 0.01
Glehen et al[96], 2010	France	Retrospective	159 (CRS + HIPEC and/or EPIC)	Nil	HIPEC:		56.0%	27.8%	6.5%	Median survival: overall: 9.2 mo, CCR0: 15 mo
					MMC 30-50 mg/m2± Cisplatin 50-100 mg/m2	60-120				5-yr survival: overall: 13%; CCR0: 23%
					Oxaliplatin 360-460 mg/m2± irinotecan 100-200 mg/m2± iv 5-FU and leucovorin
					EPIC:	30
					MMC 10 mg/m2	Day 1
					5-FU 600 mg/m2	Days 2-5
Yang et al[101], 2010	China	Prospective	28 (CRS + HIPEC)	Nil	MMC 30 mg	90-120	CCR0-39.2% CCR1-21.4%	14.3%	0%	2-yr survival - 43%
					CDDP 120 mg					Median survival (mo):
										PCI ≤ 20 vs PCI > 20-27.7 vs 6.4, P = 0.0001
										CCR0 vs CCR1 vs CCR2 and 3- 43 vs 9.5 vs 7.5, P = 0.001
Yang et al[97], 2011	China	Randomised controlled trial	34 (CRS + HIPEC)	34 (only CRS)	MMC 30 mg	60-90	58.8% each arm	HIPEC vs control - 14.7% vs 11.7%	Nil	Median survival (mo):
					CDDP 120 mg					HIPEC vs control- 11 vs 6.5, P = 0.04 (all pts)
										HIPEC vs control: 12 vs 6.5, P = 0.02 (synchronous PC)
										1,2 3-yr survival (HIPEC vs control):
										41.2 vs 29.4%, 14.7 vs 5.9%, 5.9% vs 0%
Magge et al[102], 2014	United States	Prospective	23 (CRS + HIPEC)	Nil	MMC 40 mg	100	95.6%	52%	4.3%	Median survival: 9.5 mo
										3-yr survival: 18%

MMC: Mitomycin C; CDDP: Cisplatin; CCR: Cytoreductive score; 5-FU: 5-fluorouracil; HIPEC: Hyperthermic intraperitoneal chemotherapy; CRS: Cytoreductive surgery; MMC: Mitomycin-C.