Efficacy and safety evaluation of pentoxifylline associated with other antioxidants in medical treatment of Peyronie’s disease: a case-control study

Figures & data

Table 1 Clinical and demographic features of PD patients in the three groups

Clinical features	Treatment group A (112 cases)	Treatment group B (94 cases)	Control group C (101 cases)	Statistical analysis (P-value)
				A vs B	A vs C	B vs C
Mean age ± SD (years)	53.22±12.01	53.73±10.31	53.99±11.10	0.746 (t-test)	0.630 (t-test)	0.867 (t-test)
Mean time from disease onset ± SD (months)	11.73±5.65	11.64±6.71	11.97±6.26	0.922 (t-test)	0.771 (t-test)	0.729 (t-test)
Mean plaque volume ± SD (cm^3)	0.687±0.853	0.631±0.929	0.617±0.600	0.652 (t-test)	0.493 (t-test)	0.900 (t-test)
Cases with calcification (n [%])	31 (27.6)	24 (25.53)	26 (25.7)	0.754 (χ^2 test)	0.759 (χ^2 test)	0.973 (χ^2 test)
Mean calcification volume ± SD (cm^3)	0.198±0.454	0.182±0.348	0.192±0.201	0.780 (t-test)	0.902 (t-test)	0.804 (t-test)
Cases with penile curvature (n [%])	94 (83.92)	78 (82.97)	83 (82.17)	0.853 (χ^2 test)	0.855 (χ^2 test)	0.883 (χ^2 test)
Mean angle of penile curvature ± SD (°)	26.914±13.778	26.884±12.489	26.554±11.587	0.988 (t-test)	0.852 (t-test)	0.862 (t-test)
Presence of penile pain (n [%])	65 (58.03)	55 (58.51)	58 (57.42)	0.945 (χ^2 test)	0.928 (χ^2 test)	0.993 (χ^2 test)
Mean PI-NRS score, only in patients with penile pain ± SD	4.892±2.165	4.709±2.087	4.81±3.682	0.639 (t-test)	0.879 (t-test)	0.859 (t-test)
Cases with ED (n [%])	41 (36.6)	34 (36.1)	36 (35.6)	0.948 (χ^2 test)	0.997 (χ^2 test)	0.938 (χ^2 test)
Mean IIEF-EF score in patients with ED ± SD	19.5±4.75	19.9±5.09	19.8±5.06	0.736 (t-test)	0.805 (t-test)	0.928 (t-test)
Concurrent risk factors	Number ofcases	Number ofcases	Number ofcases	A vs B (χ^2 test)	A vs C (χ^2 test)	B vs C (χ^2 test)
Dupuytren’s contracture	4	3	3	0.880	0.805	0.928
Coronary artery disease	8	7	7	0.933	0.951	0.889
Dyslipidemia	17	15	16	0.877	0.893	0.982
Diabetes	13	11	12	0.983	0.950	0.969
High blood pressure	31	28	30	0.759	0.763	0.989
Low testosterone	2	2	3	0.859	0.906	0.709
Benign prostatic hyperplasia	10	9	9	0.873	0.996	0.872
Chronic prostatitis	4	3	4	0.880	0.881	0.773
Cigarette smoking	23	21	20	0.885	0.894	0.795

Notes: Group A: PTX 400 mg twice a day + propolis 600 mg/d + blueberry 160 mg/d + vitamin E 600 mg/d + diclofenac 4% gel twice/day + PTX 100 mg via perilesional penile injection/every other week (12 injections in all); Group B: the same treatment as Group A except for the penile PTX injections; Group C: control group with no treatment. Continuous variables were compared using the two-tailed Student’s t-test whereas categorical variables were statistically compared by use of the χ² test.

Abbreviations: PD, Peyronie’s disease; SD, standard deviation; n, number of cases; PI-NRS, pain intensity numeric rating scale; ED, erectile dysfunction; IIEF-EF, index of erectile function.

Table 2 Results after 6 months of treatment

Outcomes	Treatment group A (112 cases)	Treatment group B (94 cases)	Control group C (101 cases)	Statistical analysis (P-value)
				A vs B	A vs C	B vs C
Mean pain resolution (% [n/N])	67.69 (44/65)	67.27 (37/55)	6.89 (4/58)	0.961 (χ^2 test)	<0.0001 (χ^2 test)	<0.0001 (χ^2 test)
Mean changes in PI-NRS score in patients with penile pain ± SD	−4.12±2.01	−3.40±2.03	−1.15±2.88	0.054 (t-test)	<0.0001 (t-test)	<0.0001 (t-test)
Mean onset of penile pain (% [n/N])	0 (0/47)	0 (0/39)	48.83 (21/43)	1.000 (χ^2 test)	<0.0001 (χ^2 test)	<0.0001 (χ^2 test)
Mean plaque volume reduction (% [n/N])	100.0 (112/112)	79.78 (75/94)	0 (0/101)	<0.0001 (χ^2 test)	<0.0001 (χ^2 test)	<0.0001 (χ^2 test)
Mean actual changes in plaque volume ± SD (%)	−46.99±21.23	−24.84±27.76	+123.38±238.49	<0.0001 (t-test)	<0.0001 (t-test)	<0.0001 (t-test)
Mean increase in plaque volume (% [n/N])	0 (0/112)	5.31 (5/94)	98.01 (99/101)	0.0186 (χ^2 test)	<0.0001 (χ^2 test)	<0.0001 (χ^2 test)
Mean plaque resolution (% [n/N])	0.89 (1/112)	1.06 (1/94)	0 (0/101)	0.900 (χ^2 test)	0.341 (χ^2 test)	0.971 (χ^2 test)
Mean calcification volume reduction (% [n/N])	96.77 (30/31)	70.83 (17/24)	0 (0/26)	0.0159 (χ^2 test)	<0.0001 (χ^2 test)	<0.0001 (χ^2 test)
Mean actual changes in calcification volume ± SD (%)	−54.02±30.43	−40.27±36.11	+109.29±206.16	0.131 (t-test)	<0.0001 (t-test)	0.001 (t-test)
Mean calcification resolved (% [n/N])	9.67 (3/31)	8.33 (2/24)	0 (0/26)	0.863 (χ^2 test)	0.301 (χ^2 test)	0.435 (χ^2 test)
Mean increase in volume of calcification (% [n/N])	3.2 (1/31)	0 (0/24)	80.7 (21/26)	0.374 (χ^2 test)	<0.0001 (χ^2 test)	<0.0001 (χ^2 test)
Mean appearance of new calcification (% [n/N])	0 (0/81)	0 (0/70)	33.3 (25/75)	1.000 (χ^2 test)	<0.0001 (χ^2 test)	<0.0001 (χ^2 test)
Mean improvement in penile curvature (% [n/N])	96.8 (91/94)	56.41 (44/78)	3.61 (3/83)	<0.0001 (χ^2 test)	<0.0001 (χ^2 test)	<0.0001 (χ^2 test)
Mean variations in angle of penile curvature ± SD (°)	−10.1±6.5	−4.8±5.7	+15.7±16.1	<0.0001 (t-test)	<0.0001 (t-test)	<0.0001 (t-test)
Mean variation in percentage of penile curve angle + SD (%)	−40.7±22.1	−21.7±23.5	+68.2±66.8	<0.0001 (t-test)	<0.0001 (t-test)	<0.0001 (t-test)
Mean no variation in penile curvature (% [n/N])	3.19 (3/94)	41.02 (32/78)	15.66 (13/83)	<0.0001 (χ^2 test)	0.0069 (χ^2 test)	0.0004 (χ^2 test)
Mean resolution of penile curvature (% [n/N])	6.38 (6/94)	1.28 (1/78)	0 (0/83)	0.128 (χ^2 test)	0.0304 (χ^2 test)	0.484 (χ^2 test)
Mean worsening in penile curvature (% [n/N])	0 (0/94)	0 (0/78)	80.72 (67/83)	1.000 (χ^2 test)	<0.0001 (χ^2 test)	<0.0001 (χ^2 test)
Mean onset of penile curvature in patients with no curvature (% [n/N])	0 (0/18)	0 (0/16)	94.4 (17/18)	1.000 (χ^2 test)	<0.0001 (χ^2 test)	<0.0001 (χ^2 test)
Mean improvement in penile rigidity in patients with ED (% [n/N])	92.6 (38/41)	61.7 (21/34)	0 (0/36)	0.0016 (χ^2 test)	<0.0001 (χ^2 test)	<0.0001 (χ^2 test)
Mean recovery of penile rigidity in patients with ED (% [n/N])	56.09 (23/41)	23.5 (8/34)	0 (0/36)	0.0052 (χ^2 test)	<0.0001 (χ^2 test)	0.0019 (χ^2 test)
Mean variations in IIEF-EF score in patients with ED ± SD	+3.6±3.1	+1.1±2.6	−1.4±2.1	0.0004 (t-test)	<0.0001 (t-test)	<0.0001 (t-test)
Mean variation percentage of IIEF-EF score in patients with ED ± SD (%)	+23.99±31.46	+6.94±15.33	−7.44±11.36	0.0051 (t-test)	<0.0001 (t-test)	<0.0001 (t-test)
Onset of ED in patients with previously normal penile rigidity (% [n/N])	0 (0/71)	0 (0/60)	48.0 (36/65)	1.000 (χ^2 test)	<0.0001 (χ^2 test)	<0.0001 (χ^2 test)

Notes: Group A: PTX 400 mg twice a day + propolis 600 mg/d + blueberry 160 mg/d + vitamin E 600 mg/d + diclofenac 4% gel twice/day + PTX 100 mg via perilesional penile injection/every other week (12 injections in all); Group B: the same treatment as Group A except for the penile PTX injections; Group C: control group with no treatment. Continuous variables were compared using the two-tailed Student’s t-test whereas categorical variables were statistically compared by use of the χ² test.

Abbreviations: n, patients; N, total patients; PI-NRS, pain intensity numeric rating scale; SD, standard deviation; ED, erectile dysfunction; IIEF-EF, index of erectile function.

Table 3 Side effects for each substance

Side effects	Oral PTX			Perilesional PTX injection			Oral propolis + blueberry			Oral vitamin E			Topical diclofenac sodium (4% gel)
	n	I (%)	n/N	n	I (%)	n/N	n	I (%)	n/N	n	I (%)	n/N	n	I (%)	n/N
Blood pressure dropa	1	0.46	1/216	0			0			0			0
Tachycardiaa	3	1.38	3/216	0			0			0			0
Dizzinessa	2	0.92	2/216	0			0			0			0
Skin rasha	4	1.85	4/216	0			0			0			0
Headache	2	0.97	2/206	0			0			0			0
Hot flashes	2	0.97	2/206	0			0			0			0
Vomiting	1	0.48	1/206	0			0			0			0
Dyspepsia	5	2.42	5/206	0			0			0			0
Nausea	6	2.91	6/206	0			0			0			0
Meteorism	8	3.88	8/206	0			0			0			0
Severe, widespread penile skin irritationa	0			0			0			0			7	3.28	7/213
Mild penile skin irritation	0			0			0			0			0
Penile hematoma or severe ecchymosis	0			0			0			0			0
Small ecchymosis	0			4	3.57	4/112	0			0			0
Significant penile pain after injection	0						0			0			0
Local penile edema after injection	0						0			0			0
Incidenceb		11.65	24/206		3.57	4/112								2.91	6/206
Incidence total		15.74	34/216c											6.1	13/213d

Notes: The table includes even the 17 cases of patients who discontinued treatment early due to the onset of significant side effects.

a Side effect which caused treatment to be stopped early;

b refers only to the 206 patients who completed the 6-month treatment.

c refers to all 216 patients who took oral PTX;

d refers to all 213 patients treated topically with diclofenac.

Abbreviations: PTX, pentoxifylline; n, number of cases; N, total number of patients.

Table 4 Side effects in the two treatment groups

Side effects (n)	Group Aa	Group B
Headache	1	1
Hot flashes	1	1
Vomiting	0	1
Dyspepsia	2	3
Nausea	3	3
Meteorism	4	4
Mild penile skin irritation	3	3
Penile hematoma or severe local	0	0
ecchymosis
Small ecchymosis	4	0
Severe penile pain after injection	0	–
Local edema after injection	0	–
Incidence % for each group (n/N)	16.07% (18/112)	17.02% (16/94)
Total incidence % in groups	16.5% (34/206)
A and B (n/N)

Notes:

a With perilesional injection. Group A: PTX 400 mg twice a day + propolis 600 mg/d + blueberry 160 mg/d + vitamin E 600 mg/d + diclofenac 4% gel twice/day + PTX 100 mg via perilesional penile injection/every other week (12 injections in all); Group B: the same treatment as Group A except for the penile PTX injections.

Abbreviations: n, number of cases; N, total number of cases.