Efficacy of Detoxsan® powder on diarrhea caused by gastrointestinal neuroendocrine tumors

Table 1 Patient cohort

Patient	Female	Male	Age (yr)	Grading	Functionality	Resection (cm)	HBP	Others
1	X		55	G2	yes, WD	IL, 62 + CC, 4		X
2		X	68	G2	yes, WD	IL, 40	X	X
3	X		72	G2	yes, WD	IL, 56 + CO, 11	X	X
4	X		79	G1	yes, WD	ileocecal		X
						IL + jejunum, 150
5	X		60	G1	yes, WD	hemicolectomy	X	X
6	X		65	G2	yes, WD	hemicolectomy		X
7	X		47	G2	yes, WD	hemicolectomy, 220		X
8		X	77	G1	yes, WD	hemicolectomy, 120		X
9	X		43	G2	no, WD	no		X
10		X	61	G2	MD, Serotonin	ileocecal, 40		X
11	X		73	G1	yes, WD	hemicolectomy, IL		X
12		X	57	G1	yes, WD	mid IL		X
13		X	63	G2	yes, WD	IL segments	X	X
14	X		48	G2	yes, WD	IL, 23 + CO, 31	X	X
15		X	64	G2	yes, WD	IL, 70	X
16		X	77	unknown	WD, Chromogranin	IL, 64		X
17	X		74	G2	yes, WD	IL, 18		X
18	X		78	unknown	yes, WD	no	X	X
19		X	83	G1	Chromogranin	no		X
20	X		39	G1	no, well diff.	no	X	X
Total	12	8
Average age	61.1	68.7	64.1

Grading: Of neuroendocrine tumors according to WHO classification[29]; WD: Well-differentiated neuroendocrine neoplasm; MD: Moderately-differentiated neuroendocrine neoplasm; CC: Coecum; CO: Colon; IL: Ileum; HBP: Hypertension or high blood pressure.

Table 2 Clinical parameters of the patients

Patient	Nutricion	Somatostatin	Dosage	Interval	Loperamide1	Disease	NET type	Primary			Metastases	in		PRRT
	consultation	analog				stage			Liver	Lymph	Bone	Lung	Peritoneum
1	yes	OCT	30 mg	4 wk	if required	IV	functional	midgut	x	x			x	2nd
2	yes	OCT	20 mg	4 wk	if required	IIIb	functional	midgut	x	x			x	3rd
3	yes	OCT	30 mg	4 wk	no	IV	functional	midgut	x	x	x		x	2nd
4	yes	LAN	120 mg	6 wk	no	IV	functional	midgut	x	x	x	x		2nd
5	yes	LAN	120 mg	3 wk	no	IV	functional	midgut	x		x			2nd
6	yes	OCT	30 mg	4 wk	no	IIIb	functional	midgut	x	x				4th
7	yes	OCT	30 mg	4 wk	no	IIIb	functional	midgut	x	x				3rd
8	yes	LAN	120 mg	4 wk	if required	IV	functional	midgut	x	x				2nd
9	yes	no			no	IV	nonfunctional	pancreas	x	x	x			1st
10	yes	OCT	30 mg	4 wk	no	IV	functional	midgut	x	x	x			3rd
		OCT s.c.	+ 100 µg	if required
11	yes	OCT	30 mg	4 wk	no	IIIb	functional	midgut	x				x	1st
12	yes	LAN	120 mg	4 wk	if required	IV	functional	midgut		x				2nd
13	yes	OCT	30 mg	4 wk	if required	IV	functional	midgut	x					3rd
14	yes	LAN	120 mg	4 wk	no	IV	functional	appendix		x				2nd
15	yes	OCT	30 mg	4 wk	no	IV	functional	midgut	x	x			x	3rd
16	yes	OCT	20 mg	4 wk	if required	IV	functional	midgut	x				x	2nd
17	yes	LAN	120 mg	4 wk	if required	IIIb	functional	midgut	x	x	x			2nd
18	yes	OCT	30 mg	3 wk	if required	IV	functional	CUP	x	x				3rd
19	yes	OCT	30 mg	4 wk	no	IV	nonfunctional	pancreas	x		x		x	1st
20	yes	OCT	30 mg	4 wk	no	IV	functional	CUP	x	x				3rd

¹During treatment with Detoxsan^® powder. OCT: Octreotide (Sandostatin LAR); LAN: Lanreotide (Somatuline Autogel); CUP: Unknown primary with suspicion of midgut primary; PRRT: Peptide receptor radionuclide therapy as treatment line. Determination of the disease stage according to the WHO classification[29].

Table 3 Effect of Detoxsan^® powder on the bowel movements as evaluated by patients

Patient	Empirical evaluation of the patients			Intake time (d)	Dose (g/d)	Bowel movement
	Satisfied	Uncertain	Non-satisfied			(frequency per day)
1			X	41	4 x 5	9 to 12
2			X	10	6 x 3	8 to 11
3	X			160	1 x 3	1 to 3
4		X		118	3 x 3	2 to 3
5	X			201	3 x 3	3 to 5
6		X		106	3 x 3	1 to 3
7	X			215	2 x 2	3
8	X			605	2 x 2	1 to 3
9	X			21	3 x 1	1 to 2
10	X			134	2 x 2	3 to 5
11	X			220	3 x 1	2 to 3
12	X			427	2 x 3	2 to 3
13	X			138	2 x 2	1 to 2
14	X			31	2 x 3	2 to 4
15	X			21	1 x 3	1 to 2
16	X			31	1 x 5	1
17			X	20	2 x 3	6 to 7
18		X		62	2 x 3	3 to 4
19	X			31	1 x 3	1 to 2
20	X			31	2 x 3	1 to 3
Total	15	3	3
Percentage	70.0	15.0	15.0

Responses were categorized as: Satisfied-bowel movements significantly reduced, uncertain-bowel movements not permanently reduced and non-satisfied-no improvement of defecation number.

Table 4 Diary of a 57-year-old male patient using Detoxsan^® powder over 3 mo

Detoxsan® powder intake (d)	days	Dose (g/d)	Bowel movements (frequency per day)	Empirical evaluation, daily
				Satisfied	Non-satisfied
1 to 2		2 x 2	5 to 8		2
	3 to 8	2 x 2	1 to 4	6
9 to 11		2 x 2	5 to 8		3
12 to 13		2 x 3	5 to 8		2
	14 to 26	2 x 2	1 to 4	13
27 to 28		2 x 2	5 to 8		2
	29 to 31	2 x 2	1 to 4	3
	32 to 43	2 x 3	1 to 4	12
44 to 49		2 x 3	5 to 8		6
	50 to 75	2 x 3	1 to 4	26
76 to 79		2 x 3	5 to 8		4
	80 to 87	2 x 3	1 to 4	8
88 to 91		2 x 3	5 to 8		4
	92 to 120	2 x 3	1 to 4	28
Sum of days				96	23

The dose of Detoxsan^® powder was individually adjusted. The treatment effect was assessed by the patient himself.

Table 5 Blood parameters determined before (in brackets) and after the application of Detoxsan^® powder

Patient	Serotonin (µg/L)	Creatinine (µmol/L)	Urea (mmol/L)	Sodium (mmol/L)	Potassium (mmol/L)	Calcium (mmol/L)
1	(1.554) 2.442	(58.0) 62.4	(3.1) 2.7	(139) 134	(3.7) 5.2	(2.3) 2.2
2	(ND) 940	(126.7) 142.3	(5.5) 7.3	(139) 142	(4.0) 4.2	(2.4) 2.4
3	(289) 530	(59.0) 69.8	(4.1) 5.2	(138) 133	(4.9) 4.4	(2.3) 2.2
4	(919) 718	(75.0) 92.1	(4.0) 4.8	(134) 140	(3.9) 4.0	(2.2) 2.3
5	(1.834) 1.330	(57.9) 91.9	(4.4) 5.4	(144) 145	(4.2) 3.9	(2.3) 2.3
6	(398) 540	(72.8) 91.8	(7.8) 10.4	(141) 137	(4.3) 4.1	(2.0) 2.1
7	(ND) 318	(53.0) 46.0	(3.1) 3.1	(139) 139	(3.9) 3.4	(2.3) 2.1
8	(946) 399	(167.5) 204.7	(4.7) 9.9	(142) 145	(4.2) 5.0	(2.3) 2.1
9	(394) 575	(73.2) 66.9	(3,7) 5.1	(136) 138	(4.3) 4.4	(2.3) 2.3
10	(2.500) 688	(60.5) 83.7	(3.6) 3.8	(146) 142	(3.8) 4.5	(2.3) 2.3
11	(263) 1.939	(59.3) 93.8	(6.8) 6.5	(144) 142	(4.3) 4.2	(2.1) 2.0
12	(1.102) 1.025	(85.6) 70,6	(4.1) 3.4	(143) 142	(3.9) 3.2	(2.2) 2.2
13	(1.230) 708	(70.0) 69.5	(5.4) 3.5	(144) 145	(4.0) 4.3	(2.4) 2.5
14	(1.967) 775	(46,9) 54,9	(2.6) 3.2	(142) 143	(4.4) 4.3	(2.3) 2.3
15	(2.052) 2.500	(75.1) 110.7	(4.6) 6.3	(137) 141	(3.9) 3.8	(2.3) 2.3
16	(477) 353	(58.6) 55.9	(5.8) 7.0	(144) 146	(4.2) 4.8	(2.2) 2.4
17	(1.224) 1.446	(50.3) 48.3	(3.5) 3.9	(143) 142	(4.0) 4.0	(2.3) 2.3
18	(1.185) 2.500	(52.7) 61.6	(3.5) 3.4	(143) 140	(4.2) 4.3	(2.3) 2.3
19	95 (63)	(155.0) 171.5	(8.2) 13.9	(133) 137	(4.1) 4.6	(2.3) 2.3
20	68 (64)	(75.5) 74.3	(5.3) 5.8	(144) 142	(4.5) 4.1	(2.4) 2.4

Bold values indicate that parameters were determined within a short time interval (< 30 d) before and after using Detoxsan^® powder, respectively.