372 Journal of Pain and Symptom Management Voh 9 No. 6 August 1994

Chighul Article

Prevalence and Pattern of with Cancer Pain: A Prospective Evaluation of 1635 Cancer Patients Referred to a Stefan Grond, MD, Detlev Zech, MD, Christoph Diefenbach, MD, and Albrecht Bischoff, MD Department of Anarthesiology and Operative Intensive Care, hive&& of Cologne, Cologne,

-ny

Abstnzt In a prospective study, the prevalence of 15 physical symptoms and symptom groups was eualuated in 1635 cancer patients referred to a pain clinic. In addition to pain, patients su.kred an average of 3.3 symptoms: insomnia (59%), anorexia (48%), constipation (33 %), sweating (28 %), nausea (2 7 %), dyspnea (24 %), dysphagia (20 %), mzun@ychiatSc symptoms (20%), vomiting (2OYo), urinary symptoms (14 %), dyspepsia (II%), paresis (IO%), diarrhea (60/o), prutitus (6%), and akrmatological symptoms (3%).

While symptom prevalence was infuenced by tuw site, pain intensity, and opioid treatment, only a minor relationship was seen between symptoms and gender, age, or tuw stage. The data emphasize that it is not sufficient to simply address pain during the treatment of patients with cancer pain; a we global approach to symptom management is necessaq J Pain Symptom Manage 1994;9:372-382.

Key Words Cancer pain, symptoms, palliative medicine

Inimductim

Pain is one of the most feared consequences of cancer. l p2 In far-advanced disease, 55%-95%

of patients experience severe pain.3v4 The use

of analgesic and adjuvant drugs according to

the gu!delines of the World Health Organiza-

Address rqhint requests to: Stefan Grond, MD, Klinik fiir Anaesthesiologie und Operative Intensivme- dizin, Universitit zu KGln, Joseph-Stelzmann-Strafie 9,50924 K6ln, Germany.

Accepd for publication: January 24, 1994.

tion (WHO)5 has proven to be an effective and safe method for cancer pain relief.6g

Most patients with severe cancer pain suffer from a variety of other distressing symptoms. The management of these symptoms has been described comprehensively.‘O-l4 Although cur- rent scientific literature provides fairly consis- tent data about rhe prevalence of pain in different cancer types, epidemiologic data on the prevalence of other symptoms are rare.15 Therefore, a prospective study was performed to evaluate the prevalence of 15 important symptoms and symptom groups in cancer of different sites.

0 U.S. Cancer Pain Relief Committee, 1994 Published by Elsevier, New York, New York 08853924/94/$7.00

Vol. 9No. 6 August 1994 PrtwaLence of Pain and Other Symptoms in Cancer 373

Patti ts

Between 1983 and 1990, following informed consent, all cancer patients referred to the pain clinic of the Department of Anesthesiology at the University of Cologne for treatment of “intractable” pain were included in this open prospective study.

Symptom Assessment On admission, an assessment of pain, other

symptoms, activity, and mood was performed. Pain intensity and general level of activity were graded by self-assessment using a verbal rating scale (VRS) . The prevailing mood was chosen by the patient from a list of eight items. For the evaluation of other symptoms, a standardized questionnaire was used. The patients were asked to indicate their symptoms from a list that included a total of 15 different symptoms or symptom groups. No special instruments or definitions were used to decide if the symptom was present; symptom reporting was based solely on the patient’s complaint of subjective discom- fort. Patients unable to complete the were assisted by a next of kin, nurse, or physician. Following this, the answers were discussed with the patient and details clarified.

Some symptoms were summarized in symp- tom groups, to keep the number of questions within practicable limits. The heading “urinary symptoms” included unduly frequent urination, urinary retention, and pain or burning during micturition; the heading “dermatological symp torns” included bacterial, mycotic, or viral infections, allergic or toxic reactions, and decu- bitus ulcers; and the heading “neuropsychiatric symptoms” included agitation, confusion, disori- entation, drowsiness, dizziness, delirium, sei- zures, and tremors. In the questionnaire, non- medical synonyms of the above terms were used. In evaluating neuropsychiatric symptoms, the impression of next of kin and nurses, as well as the assessment of the examining physicians, were of great importance. Anxiety, depression, and other alterations of the mood were not defined as neuropsychiatric symptoms.

Data were evaluated using a computerized database system. IE The chi-squared test and the

Patients (N= 1635)

Siteabbre- Site

Head and neck region Gastrointestinal tract Respiratory system Breast Genitourinary system Lymphatic-hematopoietic

system

liarion IQ %

HNR 236 14 cxr 507 31

RS 181 II BRS 155 GUS 263 1”s LHS 78 5

Skin, bones, connective tissue

SBC 89 5

Others or more than one OTH 126 8

one-way analysis of variance (statistical package SPSS-PC; SPSS, Chicago, IL, USA) were used to evaluate the influence of gender, age, tumor site, tumor stage, pain intensity, and opioid treatment on symptom prevalence. A value of P < 0.05 was considered significant.

Patients

During the study period, 1635 patients (843 men and 792 women) were evaluated. The mean age was 58.8 years (SD, 13.1 years; range, 13-92 years).

The patients suffered from cancer of various sites, most often of the gastrointestinal tract, the genitourinary system, or the head and neck region (Table 1). Using the TMN classifica- tion,” the tumor was stage 1 in 14 patients (l%),stage2in59 (4%),stage3in 165 (10%). and stage 4 in 1006 (62%). There was no cancer diagnosis in 11 patients (1%) and the stage could not be determined in the remain- ing 380 patients (23%). Two-thirds of the patients (N = 1093 or 67%) had undergone previous surgery; 902 (55%) had previous radiotherapy and 577 (35%) had received chemotherapy. In 220 cases (13%), no anti- cancer treatment had been applied.

All patients experienced pain on admission, 1615 continuously (Table 2) and 20 intermit- tently. Pain was experienced despite treatment with analgesics (90%) and additional coanal- gesic drugs (26%) (Table 3). The intramuscu- lar (IM) morphine equivalent dose of the

374 Gmnd et nl. W. 9 No. 6 Aqpst 1994

Table 2 pain h~tensity on Admission

Patients (N= 1635)

Pain intensity N %

None” 20 1 Mild 46 3 Moderate 162 11 Severe 542 33 Very severe 546 33 Maximal 260 16 Unknown 39 2

“20 p&n& had, due LO prior ueaunenl. no pennanenl paill on admission bui described SEVCW breakthrough or incident pain.

patients taking “weak” opioids WB 7.6 + 5.0 mg/&y and of those taking “strong” opioids 36.7 + 44.0 mg/day. The median pain intensity score was “very severe” in all pain treatment groups, specifically those receiving “weak,” “strong,” or spinal opioids. Adjuvant drugs to ameliorate symptoms other than pain were used in 43%, as indicated in Table 3.

Apart from pain, 94% of the patients suf- fered from additional symptoms; 80% experi- enced more than one symptom and 15% noted more than five symptoms (Figure 1). The average number of symptoms per patient was 3.3 f 2.1. There was no correlation between the number of symptoms and gender, age, or tumor stage (Table 4). The lowest number was seen in cancer of the skin, bone, and ccnnec- tive tissue; the highest in cancer of the respira- tory system or cancers of multiple or other sites.

Patients with pain of very severe or maximal intensity suffered from more symptoms than those with a lower pain intensity (Table 4). Patients not taking opioids described only 2.9 symptoms. This number increased to 3.4 in patients taking “weak” opioids and to 3.7 in patients taking “strong” opioids (Table 4).

Figure 2 represents the prevalence of each symptom on admission. Insomnia, anorexia, and constipation were observed most frequently.

Only 27% of the patients assessed themselves as balanced (being free of mental distress). The majority judged themselves as being dtipressed, dysphoric, anxious, or in fluctuating states of mood (Figure 3). Figure 4 demonstrates that 54% of patients experienced a severe or maximal reduction in activity.

Table 3 Analgesics, CoanaIgesics, and Adjuvant Drugs on

Admission

Drugs

Patients (N= 1635)

N %

Analgesics Nonopioids “Weak” opioids z!z nonopioids “Strong” opioids : : nonopicids Spinal opioids

Coanalgesi@ Hormonally active drugs Corticosteroids Spasmolytics Antidepressants Anticonv&ants

AdjuvantsR Hypnotics H, antagonists Laxatives Antipsychotics Antiemetics Antacids Anxiolytics

1477 90 242 15 934 57 289 18

12 0.7

429 26 150 9 115 7 96 6 71 4 37 2

707 43 305 19 169 10 i33 111 ; 108 7 77 5 65 4

“Multiple selections possible.

The influence of gender, age, and tumor stage on symptom prevalence is analyzed in Table 5. Women suffered more frequently from constipa- tion, nausea, vomiting, and neuropsychiatric symptoms, and men experienced more insomnia and dysphagia. Anorexia, constipation, neuro- psychiatric symptoms, and urinary symptoms were reported significantly more frequently in patients over 58 years of age; dysphagia occurred more often in younger patients.

Fig. 1. Number of symptoms other than pain on admission in N= 1635 patients.

0 1 2 3 4 5 6 7 a 9 IQ it 12 13 number of symptoms

VOL 9 No. 6 August 1994 PwTa!ence of Pain and Other Symptoms in Cancer 375

Table 4 Relationship of Gender, Age,

Number of symptoms

Patients (N= 1635) Mean SD Range PO

Gender Male Female

Age (yr) 558 >58

Tumor stage o-3 4

Tumor site HNR GIT RS BRS GUS LHS SBC OTH

Pain intensity None-severe Veq severe-

maximal

843 792

3.3 3.4

754 3.2 881 3.4

249 3.3 1006 3.4

236 3.2 507 3.3 181 3.7 155 3.1 263 3.3

78 3.2 89 2.8

126 3.7

790 3.2 806 3.5

Opioid Treatment No opioids 400 “Weak” opioids 934 “Strong” opioids 289 “Spinal” opioid@ 12

Total 1635

2.9 3.4 3.7 3.3

3.3

2.1 2.1

2.1 2.1

2.1 2.1

1.8 2.1 2.1 2.2 2.0 2.1 2.1 2.1

2.0 2.1

1.9 2.1 2.1 2.1

2.1

NS O-12 o-13

NS o-13 o-12

NS O-10 O-13

<0.05 O-10 o-9 o-9 o-13 o-11 O-12 o-9 o-9

<0.001 o-11 o-13

<0.001 o-9 o-13 &12 O-6

o-13

“Significance (One-way analysis of variance). bThe 12 patients receiving spinal opioids were not included in the statistical analysis. H.&, head and neck region; Gff, gastrointestinal tract; RS, respiratory system; URS, breast; GUS, genitourinary sys~ern; IA-IS, lymphatic-hematopoietic system: SBC, skin, bones, and connective tissue; and OTH, others or more than one.

The tumor stage had only little influence on symptom prevalence (Table 5). While the prevalence of dyspnea was greater in advanced cancer, the prevalence of dysphagia and dys- pepsia was even lower.

The primary cancer site had major influence on symptom prevalence (Table 6). Only the frequency of insomnia, dyspepsia, pruritus, and dermatological symptoms showed no signifi- cant differences between the subgroups.

Patients experiencing very severe or maxi- mal pain complained more frequently of in- somnia, sweating, vomiting, and paresis (Table 7). The use of strong opioids was associated with a higher prevalence of anorexia, constipa-

symptoms

Insomnia anorexia

constipation sweating

nausea dyspnoea

dysphagia neuropsych. s.

vomiting urinary s.

dyspepsia paresis

diarrhoea pruritus

dermatol s.

patients

Fig. 2. Symptom prevalence on admission in A = 1635 patients (neuropsych., neuropsychiatric; s., symptoms; and dermatol., dermatological).

tion, nausea, neuropsychiatric symptoms, vom- iting, urinary symptoms, and paresis (Table 7).

The present study evaluates the symptom prevalence in patients suffering from cancer pain. It should be noted that this is not a random selection of patients. The reason for referral to the clinic, and thus a selection criterion for inclusion in the study, was “intrac- table” cancer pain. However, the diagnosis of “intractable” pain made by the referring physicians was almost always incorrect, because the majority of the patients could be treated effectively and safely by analgesic treatment following WHO guidelines.” In the vast major- ity of patients, the disease was far advanced and no curative treatment was available. Therefore,

27%

Fig. 3. Patient mood on admission in N = 1635 patients.

mood

depressed

balanced

unclear

dysphoric

anxious

fluctuating

somnolent

euphoric

0% 25% patients

50%

376 Grond et al. I’ol. 9 No. 6 August 1994

reduction of activity

none

mild

moderate

severe

maximal

25% patients

Fig. 4. Reduction of patient activity on admission in N= 1635 patients.

our data may not be comparable to those of the literature regarding general cancer popula- tions in different stages of disease.

The study was performed in a prospective manner. Since 1983, all patients had to fill in the same list of symptoms, and the data were stored in a computerized database system.‘” This is in contrast to other studies, where only the symptoms being reported spontaneously by the patients’s or being retrospectively evalu- ated from the records19y2o were evaluated.

From a list of 15 items, patients marked an average (*SD) of 3.3 zk 2.1 symptoms or symptom groups. If pain is included as a symptom, our patients thus suffered on average from 4.3 symptoms at the time of admission. Coyle and colleagues reported that 71% of patients described three or more distinct symptoms (mean, 3.3) at 4 weeks before death.t8 Curtis and colleagues used a list that included 38 symptoms and observed that the absolute number of symptoms experienced by patients referred to a pailiative care service ranged from 1 to 25 with a median of six.21 Hadlock identified 2266 symptoms among 385 patients admitted to a hospice, for an average of 5.8 out of 136 different symptoms assessed.22 It is hardly surprising that the number of symptoms reported increases if a list of 38 or 136 items is used, instead of the 15 symptoms included in our list.

The intensity of symptoms was not consid- Table 8 compares the symptom prevalence ered in this evaluation to facilitate patient evaluated in this study with the literature. The

compliance. This is a limitation of the study, because quality of life is not only influenced by the number of symptoms but also by their intensity. In a new database, we have integrated intensity ratings of the symptoms, being mea- sured on admission as well as regularly during pain treatment.

Table 5 Frequencies of Accompanying Symptoms Depending on Gender, Age, and ‘lbmor Stage

Gender Age (years) Tumor stage

M F 558 >58 O-3 4

Patients (N) 843 792 754 881 249 1006

% % P” % % P f’ % % P”

Insomnia 61 56 <0.05 60 58 Anorexia 48 47 NS 45 50 Constipation 29 37 C3.001 29 36 Sweating 27 28 NS 30 26 Nausea 22 34 <O.OOl 26 29 Dyspnea 26 22 NS 25 24 Dysphagia 28 16 <O.OOl 24 20 Neuropsych. s. 19 23 <0.05 18 23 Vomiting 17 24 <O.OOl 18 22 Urinary s. 15 13 NS 11 18 Dyspepsia 10 12 NS 14 11 Paresis 10 10 NS 11 9 Diarrhea : 7 NS 6 7 Pruritus 6 NS 7 5 Dermatol. s. 3 4 NS 4 3

“Significance (2”). Neuqwh., ucuropsychiatric; s., sy~uptoms; aud dennatol., dcrmatological.

NS 58 61 NS <0.05 52 48 NS <O.Ol 32 34 NS

NS 31 26 NS NS 25 29 NS NS 26 <0.05

<0.05 z; 21 <O.Ol <0.05 19 20 NS

NS 16 21 NS <O.OOl 14 14 NS

NS 14 9 <0.05 NS 8 10 NS NS 5 7 NS NS 6 6 NS NS 4 3 NS

Vol. 9No. 6August 1994 Pmalence of Pain and Other Symptoms in Cancer 377

Tabke 6 Frequencies of Accompanying Sympto in ~~~fe~~~e Sites of cer

Site of tumor HNR GIT RS BRS GUS LHS SBC OTH Patients (N) 236 507 181 155 263 78 89 126

% % % % % % % % p”

Insomnia 64 60 59 54 57 44 63 60 NS Anorexia 40 50 54 35 51 49 40 56 <O.OOl Constipation 26 34 32 31 38 30 26 41 <0.05 Sweating 20 26 32 30 32 36 24 30 <0.05 Nausea 16 30 24 34 32 32 21 29 <O.OOl Dyspnea 21 19 52 28 17 19 20 28 <o.oo 1 Dysphagia 61 18 25 7 7 12 11 25 <O.OOl Neuropsych. s. 27 17 25 25 16 24 17 20 <0.05 Vomiting 10 26 17 19 23 17 20 19 <O.OOl Urinary s. 8 18 10 I1 19 12 14 14 <O.Ol Dyspepsia ; 13 11 11 11 9 6 6 NS Paresis 5 13 12 12 17 12 20 <O.OOl Diarrhea 3 10 3 6 12 1 5 <O.OOl Pruritus 7 5 8

; 4 8 3 11 NS

Dermatol. s. 4 3 2 6 3 5 5 1 NS

“Significance (chi-squared test). HNR, head and neck region; CIT, gastrointestinal uact; KS, respiratory system; BRS. breast; GUS, gcuitourinaty system; LHS, lymphatic-hematopoietic system; SEC, skin, bones, and conncctivc tissue; OTH, othen or more than one; neuropsych., neuropsychiatric; s., symptoms; and dermatol.. dennatological.

large variation emphasizes that the surveys

analyzed different populations (different sites and stages of the disease) at different points in time (on admission or at a certain interval before death), using different methods (retro- spective or prospective; using self-reports, in- terviews of primaty care givers, or records).

The largest previous survey was performed at St. Christopher’s Hospice. Summarizing the annual reports between 1975 and 1984, Twycross and Lack present the common symp- tams in 6677 patients admitted to the hos- pLci4 Saunders,” Baines,24 and Walsh2” re- port on subgroups of that collective, Using data

Table 7 Frequencies of Accompanying Symptoms Depen on Pain Intensity and Opioid Treatment

Patients (N)

Pain intensity

None- Very severe- severe maximal

790 806

% %

None

400

%

Opioids

“Weak” “Strong” Spinalb

934 289 12

% % % P”

Insomnia 52 68 <O.OOl 58 61 Anorexia 48 48 NS 43 48 Constipation 32 35 NS 25 33 Sweating 25 32 <O.Ol 20 30 Nausea 26 30 NS 21 29 Dyspnea 26 23 NS 24 z: Dysphagia 24 20 NS 25 Neuropsych. s. 21 21 NS 19 19 Vomiting 18 23 co.01 15 21 Urinary s. 15 15 NS 10 15 Dyspepsia 11 ?I 1 NS 12 11 Paresis 8 12 <O.Ol 7 9 Diarrhea 6 ; NS 8 6 Pruritus 6 NS 5 6 Dermatol. s. 3 4 NS 3 4

a Signilicance (chi-squared test). “The 12 patients receiving spinal opioids were not included in the statistical analysis. Neuropsych., neuropsychiatric; s., symptoms; and dermatol.. dennatological.

54 58 NS 54 25 <0.05 42 42 <O.OOl 30 33 <o.OOl 33 17 <o.oo 1 28 17 NS 18 8 NS 26 25 <0.05 26 8 <O.OOl 18 17 <O.Ol 8 0 NS

18 17 <O.OOl 6 8 NS 7 0 NS 3 0 NS

378 Grand et al. Vol. 9No. 6 August 1994

Table 8 Frequencies of Symptoms in the Literature

Study

Patients (N)

A B C D E F G H I

1635 6677 1592 1103 200 168 115 100 90

% % % % % % % % %

Pain 169 71 51 38 51 84 59 54

Insomnia 59 29 NA NA NA 51 16 :

7 General weakness 54” 47 NA NA NA NA 51 36 43 Anorexia ;: 67 79 31 NA 71 30 55 8

Constipation 47 54 NA NA 47 23 40 4 Sweating 28 NA NA NA 14 NA 14 NA NA Nausea 27 40 44 19 :z 51 6 32 12 Dyspnea 24 51 53 27 47 10 41 17 Dysphagia 22 23 43 22 NA 38 9 9 3 Neuropsych. s. 20 10 38 33 42 58 13 16 24

Vomiting 20 NA NA NA NA NA 4 25 NA Urinary s. 14 23 NA NA 32 37 NA NA 3 Dyspepsia 11 NA NA NA NA NA NA 17 NA Paresis 10

@ N! NA NA NA NA NA NA 25

Dry mouth 74 NA NA 48 30 46 NA Diarrhea 6 4 25 NA NA NA 5 NA <5 Pruritus 6 NA NA NA 12 NA 6 7 c5 Dermatol. s. 3 19 NA NA NA 28 NA NA NA

“Calculated from “reduction of activity” in 891 patients (Figure 4). bBased on the dam of 525 patienrs in 1991. A, this study; B, Twycro~ and Lack;r4 C, Bcuben er aL;26 D, Brescia et al.;re E, Lichter et al.;27 F, !ktle;“ G, Vent&k&la et al.;28 H, Curtis eL al.;*r I, Coyle et al.;‘” NA, not available; neuropsychiatr.. neuropsychiauic; s., symptoms; and dermatol., dermatologicat.

from the National Hospice Study, Reuben and colleagues prospectively researched this topic in 1592 terminal cancer patients being treated in a hospice or a nonhospice medical-care setting.z6 During an initial interview at study entry, the presence or absence of distinct symptoms was reported by the patients or their primary caregivers. Brescia and colleagues retrospectively studied 1103 advanced cancer patients for prevalence of symptoms on admis- sion to a hospital that cares exclusively for individuals in the terminal stage of disease.tg Lichter and Hunt prospectively examined 200 hospice patients, but in contrast to the other studies, not at the time of admission to the hospice,27 but rather in the last 48 hr of life. Seale performed interviews with the persons who were best able to give information on the last 12 months of life of 168 cancer patients20 Ventafridda and colleagues investigated 115 terminal cancer patients at the beginning of palliative care and presented the percentages of patients who reported uncontrolled symp toms on a questionnaire.2* Another prospec- tive study documented the presenting symp- toms of advanced cancer patients upon referral to a Palliative Care Service.21 Coyle and col- leagues retrospectively studied symptoms dur-

ing the last 4 weeks of life,t8 where the records of 90 consecutive patients were reviewed who had been followed by a supportive care pro- gram.

The prevalence of most symptoms in our population is fairly consistent with those re- ported in other publications. All of our patients suffered from pain, whereas the other surveys showed a lower rate of pain. The criterion for study inclusion in these studies was the need for palliative medicine, and not necessarily pain control. For instance, Reuben and col- leagues26 reported only the prevalence of bone pain (51%) and of severe uncontrolled pain (11%) , and Brescia and colleaguesi reported only the prevalence of severe pain (38%).

Two symptoms not assessed in our study, general weakness and dry mouth, are men- tioned for comparison in Table 8, because they occur frequently and their prevalence was deemed worthy of mention in four of the other studies. Instead of general weakness, we as- sessed the patient’s general level of activity (Figure 4). In our opinion, general weakness can be assumed if the physical activity is severely or maximally curtailed. Using this supposition, the prevalence of weakness in our patients was taken as 54%, which is comparable

Vol. 9 No. 6 August I994 Prevalence of Pain and &her Symptoms in Cancer 379

to 36%~51% reported in the other studies. The symptom of dry mouth was integrated into our database in I991 and was found to occur in 8% of 323 patients.

In most studies, nausea and vomiting were not assessed separately.14Js-Z0~‘G~7 Thus, the prevalence of nausea reported in Table 8 is equivalent to the prevalence of nausea and/or vomiting in other studies. As assessed in our study, the item neuropsychiatric symptoms included symptoms like agitation, confusion, disorientation, drowsiness, dizziness, delirium, seizures, and tremors. These symptoms were assessed separately in all other studies (Twycross and Lack t4: drowsiness 10%; Reuben and colleagues *? dizziness 38%, disorientation 12%; Brescia and colleaguest? confusion 33%; Lichter and I-Iunt’7: restlessness and agitation 42%, confusion 9%; Scale? drowsiness 58%, confusion 33%, dizziness 29%; Ventafridda and colleagues2s: drowsiness 13% confusion 6%, dizziness 3%; Curtis and colleagues”: dizziness 16% confusion I l%, memory prob lem 10%; and Coyle and colleaguesrs: confu- sion 24%, restlessness 6%, dizziness 1%). The prevalence of the most commonly occurring of these symptoms is included in Table 8 under neuropsychiatric symptoms, because some pa- tients suffered several neuropsychiatric syrnp toms. The variation in the prevalence of neuropsychiatric symptoms expressed from study to study probably reflects the imprecision of the instruments that were used. Further studies using better instruments will have to elucidate this point.

The assessment of emotional aspects and psychiatric disorders is important in palliative care.‘T2s Derogatis and colleaguesZm used a psychiatric interview and psychological tests and found an overall prevalence rate of 47% for psychiatric disorders among patients with cancer pain. Of those patients with a psychiat- ric disorder, 68% had an adjuntment disorder, 13% major affective disorders, 8% organic mental disorders, 7% personality disorders, and 4% anxiety disorders. In our study, no special psychological instruments were used; mood was determined by self assessment of the patients (Figure 3). This is of interest because only limited data exist on this problem. The prevalence of depression was reported by Scale*” to be 38%, by Curtis and colleagues”’ to be 31%, and by Coyle and colleagues’s to be

8%; the prevalence of anxiety was reported by Curtis and colleagues2r to be 20%, and by

Coyle and colleaguesrM to be 21%; and tbc prevalence of sedation was reported by Curtis and col]eagueP to be 7%.

Only a few studies have analyzed symptom prevalence in relation to sex. Baines*” (analyz- ing a subgroup of the St. Christopher’s pa- tientsr4) and Curtis and colleagues2r examined this topic on admission to a hospice, and Saunders’” assessed it in the last 24 hr of life. AI1 studies confirm our results, that women suffer more frequently from nausea and vomit- ing, and men more frequently from insomnia and dysphagia. The higher rate of dysphagia in men can easily be explained by their higher incidence of head and neck cancer and esopha- gus cancer. The higher rate of nausea and vomiting in women can be due to several factors, including pain, cancer type, and in- creased sensitivity to opioids and other drugs. On further analysis of this point, we found no difference in the distribution of cancer sites, cancer stages, pain ratings, or modalities of opioid treatment, which might explain the higher rate of gastrointestinal symptoms in women. In particular, the type, mode of application, and dose of opioids were inde- pendent of gender in our patients. The higher prevalence of constipation and neuropsychia- tric symptoms in women was not substantiated in other publications.

To analyze the influence of age, patients below and above the mean age (58.8 years) were compared. The younger patients suffered from 3.2 symptoms and the older from 3.4 symptoms. This difference is not significant. Other studies confirm that increasing age is not necessarily associated with a greater number of symptoms_lW?lXU~

We found a higher rate of neuropsychologi- ca1 symptoms in older patients, which is consistent with the data of Brescia and col-

leagues’” and Seale. 20 In the last 24 hr of life,

Saunders reported the rate of agitation and confusion to be higher in younger patients2”

The older patients in our study showed a higher frequency of _gastrointestinal symptoms such as constipation (PC O.Ol), nausea (P= NS) and vomiting (P = NS). This has not been confirmed by other authors.‘“~t’+25~“’ McMil- ]a# and Saunders2s found an even higher frequency of nausea and vomiting in patients

380 Grand et al. Vol. 9 No. 6 August 1994

under 55 years or 65 years, respectively, and Sealezs noted a higher frequency of constipa- tion in patients under 75 years.

The influence of tumor site and stage on physical symptoms has not been investigated in patients with cancer pain, and to our knowl- edge, no comparable data are available. Tumor growth will cause different symptoms, depend- ing obviously on the cancer site. Thus, dys- phagia was observed comparatively more fre- quently in cancer of the head and neck region; dyspnea in cancer of the respiratory system; and anorexia, constipation, vomiting, and uri- nary symptoms in cancer of the gastrointestinal tract or genitourinary system. Other observed correlations, such as the high rate of anorexia in cancer of the respiratory system, of sweating in cancer of the respiratory, genitourinary, or lymphatic-hematopoietic system; of nausea in breast cancer; of neuropsychiatric symptoms in cancer of the head and neck region, the respiratory system or the breast; and of paresis and diarrhea in lymphatic-hematopoietic tu- mors may be due to typical metastatic patterns, hormonal factors, social and psychologic inter- actions, or modalities of treatment.

In 1006 of our patients, cancer had advanced to stage 4. This group was compared with 249 patients with less advanced tumor, stage O-3. The stages 6-3 were not analyzed separately due to the small numbers in each group. Although we expected patients with far-advanced cancer to suffer from an increased number of symptoms, this was not seen in our population. An explana- tion for this finding might be found in the selection criterion for entering the study. Not the cancer stage, but ‘Mractable” pain was the reason for referral to our pain clinic. We can assume that early cancer-related severe pain is also capable of causing other symptoms. In addition, symptom control management was even worse than pain treatment, as can be seen from the small number of patients receiving adjuvants in comparison to those receiving analgesics or coanalgesics (Table 3). This may be a related explanation: due to our patient selection or due to insufftcient pain and symp tom control, patients with early cancer but “intractable” pain suffered from the same variety of physical symptoms as the patients with far advanced disease.

This is confirmed by analyzing the number of symptoms in relation to pain intensity. To

compare groups of similar size, one group consists of patients reporting very severe or maximal pain, the other of patients with a lower pain intensity. With increasing pain intensity, the number of other symptoms also increased. In particular, insomnia, sweating, vomiting, and paresis were seen more fre- quently. The higher rate of insomnia and sweating (possibly reflecting sympathetic tone) can be interpreted as being a direct conse- quence of severe pain. Patients with vomiting are probably unable to take their oml analge- sics regularly, and therefore will experience more pain. Also, paresis is seen more fre- quently with severe pain. A possible explana- tion for this relationship is that paresis is a sign of neuronal damage and, hence, reflects a higher rate of neuropathic pain, which often is experienced as being more severe than no- ciceptive pains2

Constipation, nausea, vomiting, urinary re- tention, pruritus, and neuropsychiatric symp- toms (dizziness or drowsiness) are classic side effects of opioids, and it is not surprising that all of these could be observed more frequently in patients taking strong opioids. Similar results were obtained by other authors, who described an increased rate of nausea, vomiting, or constipation during treatment with these opioids.%%S Patients who receive spinal opioids are listed in Tables 4 and 7, but are not included in the statistical analysis due to the small sample size. The use of spinal opioids in these patients did not provide adequate pain relief.

One possible conclusion that could be drawn from the relationship between opioids and symptoms is that opioids should be avoided in the treatment of cancer pain. This conclusion, however, is obviously wrong, because data are based on previous undertreatment of pain and symptoms and the incorrect use of opioids by referring physicians. Opioids given adequately according to WHO guidelines” have been shown to be highly effective and safe. No alternatives exist.

These data are important to make us aware of the risk of the potential side effects in order to anticipate them: opioids should be given regularly, with the dose titrated against the patient’s pain;4*s opioids should also be com- bined with a nonopioid analgesic if possible and with coanalgesics if appropriate.ss Other

Vol. 9 No. 6 August 1994 Prevalence o/Pain and t&r Symjltonw in Cancer 381

routes of opioid administration, sue as the

spinal, parenteral, or transdermal route,

should be considered, and a comprehensive

and prophylactic approach to control side effects is necessary (for example, laxatives, antiemetics, and antipsychotics).4*5~35

Many studies have been able to demonstrate that cancer pain relief with “strong” opioids is possible without causing severe problems from side effects.G,8*g~25 Our own data demonstrate that, although patients on oral morphine had a higher rate of side effects than those on “weak” opioids or nonopioids only, the rate of these symptoms was very low (constipation ll%, vomiting 7%, and urinary retention 4%)35 and the treatment could be continued until death.’ McIllmurray and Warren report that, despite an increase in the use of opioids during hospice stay, there was a marked reduction in nausea or vomiting, an effect attributable to the use of a variety of antiemetic drugs.34 Tolerance can also play a role in the reduction of nausea and vomiting. During long-term opioid treatment, nausea and vomit- ing are, in our opinion, most often caused by cancer or pain-related factors and not by opioids. Antiemetics are therefore probably of more importance in this situation.

Symptom prevalence in patients with cancer pain is high. Patients with advanced cancer commonly experience multiple symptoms, each of which may adversely affect function or sense of well-being. Some of these symptoms may be induced by pain therapy, whereas others are either directly caused by pain, by the cancer, or by the metabolic abnormalities that commonly occur in cancer patients.

These symptoms reduce quality of life and have a major influence on the modalities of cancer pain treatment. It is not sufftcient simply to address pain; a more global approach to symptom management is necessary. There- fore, individuals concerned with the manage- ment of cancer pain must be skilled in all aspects of palliative medicine.

?X?w

The study was supported by the German Cancer Foundation (Deutsche Krebshilfe,

Bonn). The authors and M. Thomm for thei ing this study.

es

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