Lack of Efficacy: When Opioids Do Not Achieve Analgesia from the Beginning of Treatment in Cancer Patients

Figures & data

Table 1 Demographic and Main Clinical Characteristics of 498 Cancer Patients at Baseline

	Overall Patients N=498	Early Responders N=430	Early Non Responders N=68	P-Value (NR vs R)
Age (years), mean (SD)	66.9 (11.8)	66.5 (11.9)	69.2 (10.9)	0.0903
Sex, female – n (%)	221 (44.4)	196 (45.6)	25 (36.8)	0.1739
Primary site of tumor – n (%)				0.3854
Lung/respiratory system	141 (28.3)	123 (28.6)	18 (26.5)
Digestive system	114 (22.9)	95 (22.1)	19 (27.9)
Genitourinary/reproductive system	94 (18.9)	82 (19.1)	12 (17.6)
Breast	65 (13.1)	60 (14.0)	5 (7.4)
Head/neck	42 (8.4)	33 (7.7)	9 (13.2)
Other	42 (8.4)	37 (8.6)	5 (7.4)
Presence of metastasis – n (%)	424 (85.1)	369 (85.8)	55 (80.9)
Ongoing anticancer therapy – n (%)	191 (38.4)	170 (39.5)	21 (30.9)	0.1727
Pain
Average pain intensity, mean (SD)	6.0 (1.4)	6.1 (1.4)	5.5 (1.2)	0.0013
Worst pain intensity, mean (SD)	8.0 (1.5)	7.9 (1.5)	8.1 (1.6)	0.2577
Previous pain therapy – n (%)				0.1387
No analgesics (WHO step 0)	48 (9.6)	41 (9.5)	7 (10.3)
Non opioids (WHO step I)	84 (16.9)	67 (15.6)	17 (25.0)
Weak opioids (WHO step II)	366 (73.5)	322 (74.9)	44 (64.7)
Pain therapy assigned at random – n (%)				0.5240
Oral morphine	122 (24.5)	110 (25.6)	12 (17.6)
Oral oxycodone	125 (25.1)	107 (24.9)	18 (26.5)
Transdermal buprenorphine	127 (25.5)	109 (25.3)	18 (26.5)
Transdermal fentanyl	124 (24.9)	104 (24.2)	20 (29.4)
Karnofsky Performance Status, mean (SD)	66.9 (17.0)	67.1 (17.4)	65.7 (14.5)	0.4083
≤ 40	57 (11.5)	52 (12.1)	5 (7.3)	0.3614
41–70	273 (54.8)	231 (53.7)	42 (61.8)
≥71	168 (33.7)	147 (34.2)	21 (30.9)
Any concomitant disease – n (%)	320 (64.3)	275 (64.0)	45 (66.2)	0.8993

Abbreviations: SD, standard deviation; WHO, World Health Organization.

Table 2 Early (3 Days) Responder and Non-responder Patients and Changes of PID

	PID – 3 Days
Early Responders – n (%)	430 (86.3)
Mean (SD)	51.7 (25.6)
Median (Q1–Q3)	50.0 (33.3–71.4)
Range	12.5–100.0
Early Non-Responders:	68 (13.7)
Mean (SD)	−31.1 (17.3)
Median (Q1–Q3)	−25 (−40.0 to −20.0)
Range	−80.0 to −14.3

Note: Q1–Q3: first-third quartile.

Abbreviations: PID, pain intensity difference; SD, standard deviation.

Table 3 Pain Characteristics in Early Responder and Non-Responder Patients

	Early Responders 430	Early Non-Responders 68	P-Value
Previous background opioid pain therapy – n (%)	322 (74.9)	44 (64.7)	0.0772
Neuropathic pain (DN4 Questionnaire) – n (%)	51 (11.9)	11 (16.2)	0.3165
Type of pain – n (%)			0.4532
Only nociceptive	358 (84.2)	54 (80.6)
Only neuropathic/Both nociceptive and neuropathic	67 (15.8)	13 (19.4)
Missing	5	1
Average pain at baseline			0.0013
Mean (SD)	6.1 (1.4)	5.5 (1.2)
Median (Q1–Q3)	6.0 (5.0–7.0)	5.0 (5.0–6.5)
Range	4.0–10.0	4.0–8.0
Worst pain at baseline			0.2577
Mean (SD)	7.9 (1.5)	8.1 (1.6)
Median (Q1–Q3)	8.0 (7.0–9.0)	8.0 (7.0–10.0)
Range	4.0–10.0	4.0–10.0
Number of BTP episodes in the 24h before baseline – n (%)			0.3536
0	243 (56.5)	32 (47.1)
1	44 (10.2)	6 (8.8)
2	63 (14.7)	11 (16.2)
3	41 (9.5)	8 (11.8)
>3	39 (9.1)	11 (16.2)

Note: Q1–Q3: first-third quartile.

Abbreviation: SD, standard deviation.

Table 4 Opioid ADRs Prevalence and Severity on Day 3

	Early Responders 430	Early Non-Responders 68	P-Value
Drowsiness – n (%)			0.9798
No	241 (56.0)	38 (55.9)
Little	128 (29.8)	19 (27.9)
A lot	52 (12.1)	8 (11.8)
Extremely	9 (2.1)	3 (4.4)
Confusion – n (%)			0.4913
No	325 (75.6)	54 (79.4)
Little	85 (19.8)	12 (17.6)
A lot	18 (4.2)	1 (1.5)
Extremely	2 (0.5)	1 (1.5)
Nausea – n (%)			0.0749
No	311 (72.3)	42 (61.8)
Little	92 (21.4)	19 (27.9)
A lot	20 (4.7)	4 (5.9)
Extremely	7 (1.6)	3 (4.4)
Vomiting – n (%)			0.9292
No	381 (88.6)	60 (88.2)
Little	33 (7.7)	3 (4.4)
A lot	14 (3.3)	2 (2.9)
Extremely	2 (0.5)	3 (4.4)
Constipation – n (%)			0.8337
No	265 (61.6)	41 (60.3)
Little	95 (22.1)	15 (22.1)
A lot	60 (14.0)	10 (14.7)
Extremely	10 (2.3)	2 (2.9)
Dry mouth – n (%)			0.1750
No	283 (65.8)	39 (57.4)
Little	98 (22.8)	19 (27.9)
A lot	40 (9.3)	10 (14.7)
Extremely	9 (2.1)	0 (0.0)

Notes: *p-value of the chi-squared test between the response variable and the ADR variable categorized as no/yes (little, a lot, extremely).

Table 5 Analgesic Responses on Day 7 in the 60 Evaluable Patients Classified as NRs on Day 3

	No (%)	Pain Intensity Difference
	Mean (SD)	Median (Q1–Q3)	Range
Non-responders	19 (31.7)	−14 (16.2)	0.0 (−25.0–0.0)	−40.0–0.0
Poor-responders	12 (20)	20.5 (4.6)	20.0 (16.7–25.0)	14.3–28.6
Responders	29 (48.3)	59.1 (22.6)	50.0 (40.0–75.0)	33.3–100.0

Note: Q1–Q3: first-third quartile.

Abbreviation: SR, standard deviation.