Evaluation and treatment of malignant ascites secondary to gastric cancer

Table 1 Incidence of peritoneal dissemination and ascites development due to gastric cancer

Ref.	No. of patients	Period	Country	Status of primary disease	Incidence
Development of peritoneal dissemination
Nakajima et al[10]	7060	1960-1988	Japan	After gastrectomy	14.2%
Nashimoto et al[12]	13002	2002	Japan	After gastrectomy	9.9% (related to death)
Development of ascites
Lello et al[15]	356	1980-2004	Norway	At initial diagnosis	6.2%
Yajima et al[31]	293	1988-2002	Japan	GC with T2-3 at diagnosis	15.0%
Fang et al[16]	5542	2007-2012	China	At initial diagnosis	2.6%1
				During the course of disease	3.7%1
Kitayama et al[14]	83	2006-2008	Japan	Peritoneal recurrence	40.0%
Tahara et al[13]	56	1993-1999	Japan	Peritoneal recurrence	46.4%

¹Diagnosis of malignant ascites is limited to ascites with positive cytology.

Table 2 Factors influencing development of ascites due to gastric cancer[19-26]

Increased fluid production

Increased vascular permeability due to increased VEGF and/or MMP-2/-9

Neovascularization of peritoneum

Peritoneal inflammation

Increased portal pressure due to tumor metastasis

High protein concentrations in ascites

Lower concentration of serum proteins due to undernutrition

Decreased drainage of peritoneal fluid

Obstruction of lymphatics

MMP: Matrix metalloproteinase; VEGF: Vascular endothelial growth factor.

Table 3 Systemic chemotherapy for patients with malignant ascites due to gastric cancer

Ref.	Regimen	No. patients	ECOG-PS 0/1/2	Ascites volume	Prior chemotherapy	Main findings	Grade 3 or more AE
Imamoto et al[1]	Paclitaxel1	64	24/28/12	Mean: 2906 mL (range: 122-7623 mL)	37	Positive CRB-GC: 39.1%	Neutropenia: 19.1%
						MST 5.2 mo	Hyponatremia: 19.1%
						Positive CRB-GC: 9.9 mo	Anorexia: 22.2%
						Non-response: 3.6 mo
Hironaka et al[51]	Paclitaxel1	38 (21)	12/15/11	ND	38	Ascites volume reduction: 5/21	Neutropenia: 32%
							Leukopenia: 29%
							Death within 30 d of the last administration
Takeyoshi et al[58]	Paclitaxel	24	8/4/2012	ND	14	MST: 7.2 mo	Leukopenia: 25%
	Doxifluridine2					1-yr OS: 29.2 and	Elevated alt: 12.5%
						RR: 41.7%
Iwasa et al[59]	Paclitaxel	25	1/19/5	Non: 1	7	Ascites volume reduction: 44%	Neutropenia: 12%
	Fluorouracil			Mild: 6		MST: 8.0 mo	Anemia: 12%
	Leucovorin3			Moderate: 2			Hyponatremia: 16%
				Masive: 16			Anorexia: 16%
Oh et al[60]	mFOLFOX-44	48	0-1/2: 26/22	ND	27	MST: 8.4 mo	Neutropenia 18.8% (per cycle)
						Ascites volume reduction: 35.4%	Nausea: 6.3%
							Febrile neutropenia: 2.6% (per cycle)
Yamao et al[38]	Methotrexate	37	8/24/5	ND	0	Ascites volume reduction: 35.1%	Neutropenia: 27%
	Fluorouracil5						Elevated total bilirubin: 24.3%
							Anemia: 24.3%
Nakayama et al[62]	Methotrexate	47 (23)	10/13/24	ND	8/47	Ascites volume reduction: 15/23	Leukopenia: 21.3%
	Fluorouracil					MST 211 d	Neutropenia: 19.1%
	Cisplatin6						Nausea: 2.1%
							Anorexia: 2.1%

¹Eighty mg/m² of paclitaxel intravenously on day 1, 8, 15, every 4 wk;

²80 mg/m² of paclitaxel intravenously on day 1, 8, 15, every 4 wk and doxifluridine 533 mg/m² at day 1-5, every week;

³500 mg/m² of fluorouracil, 250 mg/m² of leucovorin, and 60 mg/m² of paclitaxel intravenously on day 1, 8, 15, every 4 wk;

⁴85 mg/m² of oxaliplatin on day 1, 20 mg/m of leucovorin, 400 mg/m² of fluorouracil on day 1 and 2, followed by 600 mg/m² of fluorouracil over 22 h, every 2 wk;

⁵100 mg/m² of methotrexate and 600 mg/m² of fluorouracil intravenously, every week;

⁶30 mg/m² of methotrexate, 600 mg/m² of fluorouracil on day 1 and 8, 6 mg/m² cisplatin on days 1-14, every 4 wk. AE: Adverse event; ND: Not described; ECOG-PS: Eastern Cooperative Oncology Group performance status.