A comparison between the administration of oral prolonged-release oxycodone-naloxone and transdermal fentanyl in patients with moderate-to-severe cancer pain: a propensity score analysis

Figures & data

Figure 1 Study flowchart.

Abbreviation: WHO, World Health Organization.

Table 1 Main baseline demographic and clinical characteristics of the study population

Main characteristics	Transdermal fentanyl (N=119)	PR oxycodone-naloxone (N=191)
Age (years)	67.8 (10.7)	68.7 (9.8)
Female	53 (44.5%)	83 (43.5%)
Primary site of tumor
Respiratory system	34 (28.6%)	76 (39.8%)
Digestive system	27 (22.7%)	50 (26.2%)
Genitourinary system	24 (20.2%)	32 (16.8%)
Breast	10 (8.4%)	10 (5.2%)
Head, neck	12 (10.1%)	10 (5.2%)
Others	12 (10.1%)	13 (6.8%)
Metastases	99 (83.2%)	160 (83.8%)
Previous anticancer therapy	91 (76.5%)	134 (70.2%)
Surgery	55 (60.4%)	70 (52.2%)
Chemotherapy	70 (76.9%)	107 (79.9%)
Biologic medical products	17 (18.7%)	21 (15.7%)
Hormone therapy	12 (13.2%)	17 (12.7%)
Radiotherapy	35 (38.5%)	48 (35.8%)
Other	4 (4.4%)	7 (5.2%)
Karnofsky Performance Status	67.4 (17.3)	66.3 (16.5)
Previous pain therapy
No therapy (WHO-Step 0)	13 (11.1%)	26 (13.6%)
Non-opioids (WHO-Step I)	21 (17.8%)	75 (39.3%)
Weak opioids (WHO-Step II)	84 (70.5%)	90 (47.1%)
Adjuvant pain therapies	54 (45.4%)	92 (48.2%)
Steroids	32 (56.3%)	64 (69.6%)
Anticonvulsants	9 (16.7%)	16 (17.4%)
Antidepressants	6 (11.1%)	14 (15.2%)
Bisphosphonates	7 (13.0%)	10 (10.9%)
Other	8 (14.8%)	10 (10.9%)
Pain duration (months)	3.2 (4.5)	3.3 (3.7)
Average pain intensity, NRS	6.2 (1.5)	6.2 (1.1)
Type of pain
Only nociceptive	102 (85.7%)	155 (81.2%)
Only neuropathic	–	–
Mixed	17 (14.3%)	36 (18.8%)
Breakthrough pain	55 (46.2%)	82 (42.9%)
Constipation	31 (26.1%)	74 (38.7%)

Note: Values are mean (±standard deviation) or number of patients (%).

Abbreviations: NRS, numerical rating scale; PR, prolonged release; WHO, World Health Organization.

Table 2 Study adherence

	Transdermal fentanyl (N=119), n (%)	PR oxycodone-naloxone (N=191), n (%)
Completed the 28-day study	87 (73.1)	147 (76.9)
Premature treatment discontinuation	27 (22.6)	25 (13.1)
Reasons for discontinuation
Noncompliance	1 (3.7)	3 (12.0)
Refusal	0 (0)	1 (4.0)
Death	10 (37.0)	1 (4.0)
Other	4 (14.8)	2 (8.0)
Inadequate analgesia	8 (29.6)	7 (28.0)
Severe ADRs	4 (14.8)	4 (16.0)
Inadequate analgesia and severe ADR	0 (0)	1 (4.0)
Difficulty swallowing	0 (0.0)	6 (24.0)
Lost to follow-up	5 (4.2)	19 (9.9)

Abbreviations: ADRs, adverse drug reactions; PR, prolonged release.

Figure 2 Mean pain intensity score (11-point numerical rating scale) throughout observation after transdermal fentanyl and prolonged-release oxycodone-naloxone.

Abbreviation: OXN, oxycodone-naloxone.

Table 3 Clinical measures and end points

	Transdermal fentanyl (N=119)	Oral oxycodone-naloxone (N=191)	p-value
Responders	75.3% (3.7)	82.9% (2.9)	0.11
Clinical success	27.8% (4.4)	36.5% (3.4)	0.12
Starting opioid dose (mg/day)a	53.0 (1.3)	25.4 (1.0)	<0.0001
Final dose (mg/day)a	113.6 (4.9)	44.5 (3.9)	<0.0001
Mean dose increasea	2.5 (1.8)	0.4 (1.4)	<0.0001
OEI >5%a	37.9% (4.1)	19.3% (3.2)	<0.0001
Patients requiring additional opioids	37.1% (4.4)	28.2% (3.4)	0.12
Patients requiring adjuvant drugs	83.7% (3.5)	82.4% (2.8)	0.78
Switches	14.1% (3.1)	10.6% (2.4)	0.37
Premature discontinuations due to ADRs	2.8% (1.2)	0.9% (0.9)	0.22
Severe constipation	32.6% (4.2)	24.7% (3.3)	0.15

Notes:

Values are percentage or number (standard error);

a around-the-clock daily doses (as oral morphine-equivalent daily dose).

Abbreviations: ADRs, adverse drug reactions; OEI, opioid escalation index.

Figure 3 Transdermal fentanyl and prolonged-release oxycodone-naloxone daily dosages (expressed in oral morphine-equivalent daily dose).

Abbreviations: OMEDD, oral morphine-equivalent daily dose; OXN, oxycodone-naloxone.

Table 4 Patients with adverse drug reactions in each treatment arm

	Transdermal fentanyl (N=119)	Oxycodone-naloxone (N=191)	p-value
Drowsiness
Any degree	68 (57.1)	113 (59.2)	0.72
Severe	24 (20.2)	37 (19.4)	0.86
Confusion
Any degree	45 (37.8)	69 (36.1)	0.76
Severe	8 (6.7)	17 (8.9)	0.49
Nausea
Any degree	55 (46.2)	64 (33.5)	0.02
Severe	15 (12.6)	17 (8.9)	0.29
Vomiting
Any degree	28 (23.5)	28 (14.7)	0.05
Severe	10 (8.4)	11 (5.8)	0.36
Constipation
Any degree	76 (63.9)	115 (60.2)	0.51
Severe	36 (30.2)	50 (26.2)	0.43
Dry mouth
Any degree	66 (55.5)	79 (41.4)	0.02
Severe	29 (24.4)	23 (12.0)	0.01
Hallucinations
Any degree	3 (2.5)	14 (7.3)	0.07
Severe	–	2 (1.1)	0.26
Muscle spasm/myoclonus
Any degree	15 (12.6)	27 (14.1)	0.70
Severe	5 (4.2)	3 (1.6)	0.26
Gastralgia
Any degree	26 (21.8)	42 (22.0)	0.97
Severe	4 (3.4)	8 (4.2)	0.22
Dysuria
Any degree	13 (10.9)	19 (10.0)	0.78
Severe	4 (3.4)	5 (2.6)	0.24
Breathlessness
Any degree	21 (17.6)	23 (12.0)	0.16
Severe	4 (3.4)	4 (2.1)	0.22
Itching
Any degree	13 (10.9)	17 (8.9)	0.55
Severe	3 (2.5)	3 (1.6)	0.26

Note: Data presented as n (%).