Cancer pain - opioid therapy


E. Bruera. C.M. Neumann, J. Hanson, Univ of Alberta, Edmonton, Canada; R. Wenk, M. Bertolino, FEMEBA Palliative Care Program, Buenos Aires, Argentina; M.A. Rico, Hospital Caupolican Pardo, Santiago, Chile; J. Moyano, National Cancer Inst, Bogota, Colombia

Aim of Investigation: To assess the safety and efficacy of ME in OR for cancer PTS in 3 Latin American countries.

Methods: 85 PTS have been admitted to this open trial of progressive oral ME titration over 3 days. PTS were observed for a 56 days and pain, nausea, sedation, bowel movements, previous opi-oid dose, ME dose, and side effects were recorded.

Results: The median Morphine Equivalent Daily Dose (MEDD) of the previous opioid on day 0 (before ME OR) was 43mg (range 10-4170). The most frequently used opioids were morphine (n=44), codeine (n=15) and tramadol (n=14). Median ME daily dose at day 7 (after OR was completed) was 17.5 (0-1200)mg. Median MEDD day 0/ME day 7 ratio was 2.6 (0-120). Univariate correlation between MEDD log at day 0 and dose ratio log was 0.74 (p=0.0001). During day 0 and day 7 pain intensity was 6.5±2 vs 2.4±2 (p<0.01) for VAS 0-10 and 2.5±1 vs 1±1 (p< 0.01) for categorical 0-4, nausea VAS 0-10, 1.3±2vs 1-i-2(p=ns) and 2.7±2vs3.4±3(p-0.07) for sedation VAS 0-10, respectively. No difference was observed in daily number of bowel movements between day 0 and day 7. 83/85 PTS (98%) completed the OR (98%) in a median of 1 (range 1-6) days. Median follow-up after OR was 33 days. 50 PTS did not complete the 56 day observation period due to ME side effects (11, 22%), death (16, 32%), lost to follow-up (7, 14%) or other reason (16, 32%).

Conclusions: Most PTS require at least one OR before death due to insufficient analgesia or side effects. ME is a synthetic opioid ago-nist with excellent oral bioavailability, no known active metabo-lites and a much lower cost as compared to other opioids. Its use is limited by a prolonged and unpredictable half life. Based on this study, we conclude that OR to ME is safe and effective in this group of seriously ill terminal cancer PTS in 3 Latin American countries.

Acknowledgment: Supported by Mallinckrodt Inc.


H. Colucci. Pharm D, Purdue Pharma L.P., Norwalk, CT 06850; E Lester*, Lakeland Medical Center, St. Joseph, MI 49085; A Miller*, Regional Oncology, Orlando, FL 32822; P Pickens*, Abington Hematology-Oncology Assoc., Abmgton, PA 19001; W Tester*, Albert Einstein Medical Center, Philadelphia, PA 19141; USA

Aim of Investigation: To compare the efficacy and safety ofcon-trolled-release oxycodone (OxyContin®) tablets (CR) ql2h with immediate-release oxycodone/APAP (Percocet®) tablets (IR/APAP) qid in patients who were opioid-naive (non-opioid analgesia), receiving low dose opioid analgesics, or fixed dose opi-oid/non-opioid combinations (<20mg oxycodone/day).

Methods: Multicenter, randomized, double-blind, parallel-group study in patients with cancer pain. Dose was titratcd up to 10 days to obtain analgesia without unacceptable side effects. Evaluation of optimum dose for up to 10 days was measured by stable pain relief (none to slight pain for 48 hours), mean daily pain intensity (PI), overall PI, and PI at end of each treatment period. Safety was evaluated by adverse events (AE), vital signs and elicited opi-oid-related side effects.

Results: 60% of patients, CR (n=44) and IR/APAP (n=41), achieved stable pain relief in 7 days (median). Mean CR dose was 29 mg/day, mean IR/APAP dose 33 mg/day. Total decrease in PI score from baseline was significant for CR and IR/APAP. No difference was noted in AE incidence between treatments (CR 47.7%; IR/APAP 39.0%). Six specific elicited opioid-related side effects were rated at a low level of severity for both CR and IR/APAP.

Conclusions: Patients were able to titrate a dose ofCR or IR/APAP without unacceptable AE. Both treatments were equally effective in controlling pain. Since the oxycodone daily doses were similar for both treatments, APAP did not seem to provide measurably additional efficacy to the IR/APAP formulation.

Acknowledgment: Study sponsored by Purdue Pharma L. P., Norwalk, CT 06850, USA.


Cordeiro, SM Moraes, Tania, Watanabe AGK., Matos FAA, Pain Clinical, Santa Casa Medical Br.

Aim of Investigation: Evaluation ofresponsiveness and acceptance of cancer patients' families about the use of opioids and previous notions and expectations about a pain treatment service.

Method: An open questionnaire was used in interviews of families of oncological patients that were beginning the use of opioids for treatment of cancer pain.We know that morphine is a medication that is used for unbearable pain, 6,6% morphine is a medication for cancer wanted to detect knowledge, prejudice to the use of morphine and expectations relative to a Pain Treatment Service.

Results: Preliminary data made with showed that 15 families interview. 33,3% think that morphine is a pain killer, 33,3% believe patients, 13,3% it used only for terminal patients, 13,3% never heard about morphine, 100% don't have fear to administrate morphine, 53% don't know what is a Pain treatment Service, 26,6% believe that a Pain treatment Service is for treat pain, 13,3% the Pain Treatment Service is going to help the patient, 6,6% the Pain treatment Service is useful to give sedation for the patient. This questionnaire will be used until 1999 June.

Conclusion: Most of the families have a basic knowledge that morphine is used to the treat pain, but they don't know what a Pain Treatment Service, is so we need more teaching programs for communities showing the importance of a Pain Service including in developing guidance protocols or families of cancer patients that will be using morphine, perhaps for long period of their disease.


Tess Cramond. Gordon Stuart2*, Bronwyn Williams, Multidisciplinary Pain Centre & Dept of Neurosurgery\ Royal Brisbane Hospital, Brisbane, Queensland 4029, Australia.

From being one of the rarest cancers, the incidence of meso-thelioma, a malignant tumour of the pleura or peritomeum, is increasing throughout the industrial world. Australia has a high incidence. The Australian Mesothelioma Register (01.01.86-31.10.98) records 3745 cases. Proven asbestos exposure was recorded in 85% of these cases. Mesothelioma affects not only men but also women, for many of whom the only exposure to asbestos was washing their husbands' overalls.

Pain and dysphagia are the commonest presenting symptoms, but lethargy, dysphagia, profuse sweating and the discomfort of tumour masses must also be addressed.

Our experience in the care of patients with mesothelioma spans 25 years and confirms the importance of the early development of a management plan to control pain and other distressing symptoms. Percutaneous cervical cordotomy will provide the most effective pain control if patients are referred early, but unfortunately referral is often late when respiratory function is compromised and cordotomy contraindicated. For these patients intraventricular morphine will provide effective analgesia.

Collaboration of respiratory physicians, radiation oncologists, neurosurgeons, psychiatrists and pain management consultants will ensure optimum care for the patients.


Dezso EmbeyIsztin. National Inst of Oncology, Pain Clinic, Budapest, Hungary

Aim of Investigation: This study was designed to determine the daily morphine dose by using immediate release morphine tablets: Sevredol.

Methods: 25 opioid naive cancer patients were investigated. 15 female, 10 male, age: 41-75, the type of pain was: nociceptive: 7 pts., nociceptive andneuropathic: 17 pts., neuropathic 1 pt. One dose of 10 mg i.r. morphine tablet was administered every 4 hours during a period of 4 days, an additional rescue dose of 10 mg was given any time if required. At the end of the fourth day the dose of the daily oral morphine was established individually for each patients. After that a milligram to milligram conversion rate was used changing from i.r. morphine to controlled release morphine: MST Continus.

Results: Having finished the titration, the quantity of daily oral morphine was: 20 mg: 1 pt., 50mg: 3 pts., 60 mg: 12 pts., 70 mg: 1 pt., 80 mg: 4 pts., 90 mg: 1 pt., 120 mg: 3 pts. If we start oral morphine treatment with slow release tablets, the usual starting dose for adults pts: 2x30 mg. In our study the 60 mg oral mo. dose was adequate only for 12 pts, 4 pts. needed less than 60 mg, 9 pts. needed more than 60 mg. It is worth to mention that only 6 pts. complained of mild nausea.

Conclusion: For opioid naive pts. starting oral mo. treatment has to be carried out by using immediate release morphine sulphate tablets in order to establish individualized oral dose and to minimize the side effects.


M. Escher*. V. Piguet, J. Desmeules, M. Kondo*, G. Scharer*, C. Favario*, P. Dayer, (SPON: E. Roux), Multidisciplinary Pain Center, Univ Hospital, CH-1211 Geneva 14.

Aim of Investigation: To determine retrospectively the reasons for a therapeutic adjustment (TA), i.e. dose reduction or opioid rotation, in cancer patients treated with morphin (MO).

Methods: The files of 110 cancer patients hospitalized in 1998, referred to a pain consultation and treated with MO were reviewed.

Results: A TA occurred in 48% of patients; 25% received another opioid. Major reasons for TA were 1) adverse effects (AE) (53%) 2) reduced requirements (24%) 3) MO refusal (11%), and 4) galenic problems (15%). AE occurred in 41 patients (37%); 13 (32%) needed no TA. Among the others, two thirds ofTA were due to nausea and/or vomitine 09%') or sedation (27%').


No adjustment



Male 41 (69%) 29 (55%)  
Female 18 (31 %) 24 (45%)  
Mean age (years) 59 63   
Chronic renal failure # 6 (12%) 13 (28%) .05
Nociceptive pain 38 (64%) 31 (58%)  
Mixed (+neuropathic) pain 21 (36%) 22 (42%)  
Controlled pain* 43 (73%) 46 (87%)  

NB: 2 patients refused to have morphin.
# - (creatinine >101 or clearance <50).
* - 50% on AVS or intensity allowing usual daily activities.

Conclusions: Chronic renal failure is the major factor associated with a therapeutic adjustment of morphin. Adverse effects are the main but not the only reason for adjustment. Morphin prescription needs individualization and opioid rotation is an option to be considered when faced with some problem.


M. Frank, W. Fleischer, Med. Dept., Mundipharma GmbH, 65549 Limburg, Germany

Aim of Investigation: The present open multicentral therapeutic study (drug monitoring) was carried out with established medical practitioners to document the efficacy of delayed action Oxyco-done (10, 20, 40 mg sustained release tablets) in the therapy of persistent pain conditions. It was to be demonstrated whether a sufficient analgesia could improve the overall condition/daily activity.

Methods: Adults of both sexes suffering from persistent severe pain conditions of malign and non-malign origin for whom opioid therapy was intended were included in the study. Pain intensity was documented by a numeric rating scale (0 = no pain, 10 = worst pain). Overall condition, daily activity, quality of sleep and ability to work were included as criteria for the quality of life. Active questioning on any possible undesirable side effects. Period of monitoring/therapy: 3 weeks. Interim assessment after 1 week.

Results: Based on data from 1279 patients drug efficacy was evaluated upon the completion of therapy. Pain intensity decreased on average from 6,9 ± 1,8 NRS at baseline to 3,0 ± 2,1 at end of therapy. Efficacy was rated by patients in 32 % of the cases as "very good", in 41 % as "good" and in 8 % as "poor". For toler-ability patient ratings were "very good" in 36 % of the cases, "good" in 43 % and "poor" in 9 %. Practitioner and patient assessments tended to be identical. All criteria for the quality of life improved considerably (at the outset overall condition/daily activity 6,8 ± 2,0 NRS (0 = no impairment 10 = max. impairment); after 3 weeks 3,4 ± 2,2 NRS). The daily Oxycodone dose after 3 weeks was in 73 % of the cases 20-60 mg, in 12 % 61-120 mg and in 15 % other dosages. As undesirable side effects nausea (week 1: 4,5 %; week 3: 1,6 %), constipation (week 1: 2,7 %; week 3: 2,1 %), emesis (week 1:2,6 %; week 3: 0,9 %) were most often reported. The incidence of side effects decreased in the course of time. Conclusion: The study could demonstrate that orally applied sustained release Oxycodone is effective as analgesic and well tolerated when applied for severe pronounced persistent conditions of pain of different etiology. In the main a daily dose of 20-60 mg proved sufficient. A clear improvement in the quality of life parameters was reported.


Fukuda CL: Pimenta CAM. (SPON C Ferandes Correa) Nursing School of Univ of Sao Paulo, A v Dr Eneas de C Aguiar,419, 05403-000, Sao Paulo, Brazil

Aim of Investigation. To analyze the constipation in oncolologic pain patients receiving different protocols ofanalgesia

Methods Patients were divided in 2 groups according the protocol prescribed for pain control The Group I patients (n=26), received opioids, NSAIDs, antidepressants and neuroleptics The Group 2 patients (n=17) received NSAIDs, antidepressants and neuroleptics The constipation were assessed by Constipation Assessment Scale (McMillan, Willians, 1989)

Results The groups were similar in sex, age, occupational activities, per-capta income, schooling, intensity and duration of pain complain, Kamofsky Index, pattern of bowel elimination before pain therapy, food and oral fluids ingestion and in the daily dose of NSAIDs, antidepressants and neuroleptics The average dose of morphine sulfate was 34 Omg and the average of length of use was 6 6 months The groups were different in constipation index (p=0 01) and in the present use of laxatives measures (p=0 03) Constipation was twice and half more frequent in patients receiving opioids compared with those receiving NSAIDs, antidepressants and neuroleptics. Were observed positive correlation between constipation index and opioids dose (r=0 46/ p=0 002)and length of use (r=0 32/ p=0 03)

Conclusion Although be known that the constipation is a frequent adverse reactions of the opioids, antidepressants and neuroleptics, there are few studies that measure and descnbe the characteristics of constipation related to these drugs We observed that constipation was undertreated


Pal Klepstad*. Fetter C Borchgrevmk*, Stem Kaasa* (SPON L Rustad), Dept ofAnesthesiology and Unit for Applied Clinical Research, Norwegian Univ of Science and Technology, 7006 Trondheim, Norway

Aims of investigation To investigate the effect from start of morphine on cancer patients' health-related quality of life (HRQL)

Methods We included 40 patients with malignant disease and intolerable pain despite treatment with weak opioids The patients were titrated to pain relief using immediate-release (IR) morphine before switched to slow-release (SR) morphine in the same daily dosages HRQL was measured by the EORTC QLQ-C30 questionnaire before start of morphine (baseline), at stabilized IR-morphine and 3 after start ofSR-morphme

Results Mean age of the patients was 63 years (range 34-78) Mean titration time was 2,3 days (1-6) and daily morphine dosage was 96,9 mg (60-180) The EORTC QLQ-C30 HRQL scores observations are presented in the table (mean (SD))

  Baseline  IR-morphine SR-morphme
Functioning Scale
Physical 31 (27) 33 (27) 35 (30)
Role 33 (33) 32 (37) 32 (37)
Emotional 85 (19) 83 (21) 87 (19)
Cognitive 76 (28) 77 (19) 77 (27)
Social 56 (30) 54 (33) 51 (30)
Global health* 40 (21) 49 (17) 44 (19)
Symptoms scales and items
Fatigue 47 (22) 50 (21) 45 (25)
Pain*,** 65 (22) 43 (26) 41 (26)
Nausea/vomiting* 9 (16) 21 (29) 18 (26)
Dyspnea 20 (30) 18 (22) 20 (27)
Sleep disturbance 21 (27) 15 (28) 16 (26)
Appetite loss 46 (36) 41 (35) 41 (37)
Constipation* 29 (35) 51 (33) 42 (33)
Diarhoea 10 (21) 6 (21) 3 (17)

Higher score = higher level of function/symptom (0-100)
* Significant difference before vs IR morphine
** Significant difference before vs SR morphine

Conclusion After start of morphine the patients besides pain relief only reported transient increases in nausea/vomiting, constipation and global health Thus, pain relief from morphine have no major influence on other aspects of health related quality of life in cancer patients


Shashidhar H Kon. H Lee Moffit Cancer Center, Tampa, FL 33612, L R Baneras*, Ft Lauderdale, FL 33308, F Lahvis*. Healthcare Center at Christiana, Newark, DE 19713 Rob en F Reder, Purdue Pharma L P , Norwalk, CT 06850, Christopher Seidler*, Fallon Medical Center, Worcester, MA 01608, USA

Aim of Investigation To study the clinical use of around the clock therapy with CR oxycodone in opioid-naive patients.

Methods Sixty eight patients in need of around the clock opioid therapy and who were opioid naive or relatively opioid naive were treated with CR oxycodone dosed ql2h The goals were to ascertain the treatment outcome and also to test the proposed dosing instructions (package insert) prior to approval to market

Results The overall duration of therapy was 62 days (range 2-531 days) The average total daily dose was 19 mg at baseline and 60 mg at the end of treatment Forty-three patients reached stable pain control in an average of 5 days Eleven of 68 (16%) discontinued due to lack of effective pain control CR oxycodone therapy significantly reduced pain and improved quality of life parameters Fifty four percent (54%) of patients said CR oxycodone was better than previous medication, 34% said it was the same as and 13% said it was worse Of 68 patients, 31 (46%) reported a total of 65 adverse events Fourteen patients (21%) discontinued because of adverse events The dosing instructions as written were judged to be very useful

Conclusions CR oxycodone can be utilized as part of the therapeutic regimen in the treatment of chronic pain syndromes in patients who are opioid-naive or relatively naive There were no specialized efficacy or safety findings in this cohort compared to patients who are already being treated with around the clock opioid therapy

Acknowledgments This study was supported by a grant from Purdue Pharma L P Dr Reder is an employee of Purdue


P La Russo*. C Davis2, D Vergidis3 (Spon: M Travers) Wayne State Univ, Detroit, MI 48201, USA; countess Mountbatten House, Southampton, S03 3JB, UK; W Ontario Cancer Center, Thunder Bay, P7A 7T1, Canada.

Aim/method: Concerns have been raised about the safety of switching patients directly from weak opioids to sustained-release strong opioids (e.g. Duragesic or MS Contin). We are undertaking a randomised 28-day study of 176 cancer patients to compare the efficacy, side-effects and patient opinions of transdennal fentanyl and sustained-release morphine in this situation.

Interim results: Data are available from 62 patients randomised to sustained-release (12-h) oral morphine (30mg bid, n=30) or transdennal fentanyl (25ug/hour, n=32). Immediate-release morphine was available as rescue medication at all times. The most common adverse events (AEs) were nausea (27), constipation (21), vomiting (20) and somnolence (16). One moderate AE (pruritus) was considered definitely related to fentanyl; 15(11 moderate, 4 mild) were considered definitely related to morphine (constipation 6, somnolence 5, nausea/vomiting 2, confusion 1, visual disturbance 1). Thirty-five serious adverse events (SAEs) were reported (19 morphine, 16 fentanyl): 4 of these were considered related to morphine either definitely (somnolence) or possibly (hallucinations, hemorrhoids and intestinal obstruction). One SAE (confusion) was considered possibly related to fentanyl. Median respiratory rates at 12 hours, 24 hours, 36 hours and 7 days did not vary significantly from baseline or between groups (median values 18-20 breaths per minute). Two patients on morphine had rates <10bpm. These were not considered clinically significant and morphine doses were not changed.

Full results: on efficacy and patient preferences from 176 patients will be presented at the meeting.

Acknowledgment: This study is funded by the Janssen Research Foundation


D. Lossignol*. M. Obiols*, J.J. Body* (SPON: P. Ewalenko), Supportive Care Unit and Pain Relief Unit-Institut Jules Bordet, 1, Rue Heger Bordet, 1000-Bruxelles, Belgium

Aim of Investigation: The role ofN-Methyl-D-Aspartate (NMDA) receptor is now well established in the development of chronic pain (Wind-up phenomenon). Although NMDA antagonists have been used in the treatment of some chronic pain syndromes, there is no prospective study in the cancer pain field.

Methods: We used ketamine in the treatment of intractable cancer pain syndromes in 15 patients (age: 32-72, mean 65.2yrs) receiving high doses of morphine (median: 600mg/d IV) but with no adequate pain relief, despite doses escalation and/or drugs association or with intolerable side effects. All patients had a VAS (visual analog scale) for pain above 7/10 and had breakthrough, or excruciating pain. We started with a test-dose of ketamine (5 mg IV). VAS decreased below 2/10 in all cases. The test was followed by a continuous infusion of 1.5 mg/Kg/day, mixed with morphine.

Results: All patients experienced durable pain relief with no side effects, except a "disconnection feeling" during the test dose phase and a problem of loss of memory in one patient. Vital parameters (Cardiac rhythm, blood pressure) were not altered. An evoked nystagmus was present in all cases during the test phase. Ten patients (67%) were able to go home with a portable pump (PCA Pump). A long term treatment (more than 6 months) was feasible in 5 patients (33%).Dose escalation was necessary in all cases, essentially because of tumor progression.

Conclusions: Those promising data suggest that other pain syndromes should be studied in order to understand the mechanism of severe pain syndromes and for a better understanding of the tolerance mechanism. Ketamine could be especially useful for the treatment of the rare, but distressing, cases of intractable cancer pain. We suggest to include NMDA antagonists into the WHO ladder.


Peter Martin*, Michael Ashby, Kate Jackson. McCulloch House, Monash Medical Centre, and Dept of Medicine, Monash Univ, Clayton, Victoria

Aims of the Investigation: To examine if the efficacy of the practice ofopioid substitution (OS) can be explained by effective dose reduction.

Methods: This study formed part of a prospective audit of patients in a palliative care unit from February 1998 to June 1998 who underwent OS for intolerable adverse effects (nausea, vomiting, confusion and drowsiness), after exclusion of other treatable causes and when standard supportive measures had failed. Pain, nausea, vomiting, confusion and drowsiness were assessed at 4 hourly intervals and all drugs, opioid and non-opioid, were recorded. Patients were assessed as responders or non-responders by comparing pre and post OS records. All opioid doses were converted to the equivalent parenteral morphine dose per 24hrs using standard conversion factors and the ratio of standardised pre and post OS doses calculated.

Results: Of 49 substitutions (including 31 morphine to fentanyl and 10 morphine to oxycodone) adverse effects improved in over 65% while pain control was as good or better. The log dose response curve for opioid analgesics supports the clinical belief that dose must increase by at least 30% to improve analgesia. According to this clinical definition, the standardised dose was substantially higher after substitution for half the people who responded, and more than doubled for a third. In contrast, three-quarters of the non-responders received a dose equal to, or less than the pre-substitution dose.

Conclusions: Our results suggest a mechanism other than effective dose reduction as the explanation for the efficacy of OS.


Mauricio G*, Arbaiza D. Zamora R* and Munoz R. Neurooncology Dept. Institute Nacional de Enfermedades Neoplasicas. Av. Angamos Este 2520. Lima- 34- Peru.

Introduction: The cancer pain requires the use ofdiferent therapies for an appropriate control. The presence of oral intolerance is frequent in patient that obliges the use of a parenteral route. The intravenous route is inpractical and expensive, while the intramuscular route is unacceptable due to it's prolonged use. On the other hand, the PCA is an effective method that utilizes less morphine dose. The objective of the study is to evaluate the efficacy and tolerability of morphine administrated subcutaneously in patients with uncontrolled cronic cancer pain and with oral intolerance.

Methods: This is a prospective and open clinical study in ambulatory patients that use a SC device for manual application of a sulfate solution of morphine every four hours with the posibility of an extra dose it intense pain is present. The morphine was prepared in sodium cloride 9 o/oo, in concentrations that varied from 0.1%, 0.5%, 1% and 2% with an application volume no larger than 3 cc. The SC device (Scalp) covered with an adhesive (tegaderm) was changes every 10 days. The morphine dose that we dispensed depended on each clinical case. The patient and family member were instruted to administer the morphine at home. We measured the response of the treatment with a visual numerical color scale (VNCS), the duration of pain during the day and the following variables dream, appetite, physical activity and sensation of good being The evaluations were performed on day 0, 15, 30 and 45

Results. We recruited 16 patient, 10 womans and 6 mans, somatic pain was found in 11 and visceral in 5 The age average was 48 years The neoplasias were breast 4, kidney 3, esophagus 2, prostate 2 , maxilar sinus, lung, leukemia, melanoma and galbladder biliary each one with one case. All were in the stage IV In the initial evaluation all had an pain intensity of 7 to 10, 13 patients had alterations of the appetite and all one alteration of the sleeps, sensation of good being and physical activity Dunng the treatment the pain intensity was 4 to 6 in only one patient, 1 to 3 in 11 patients and no pain in 4 Two patients had alterations of the sleep and sensation of good being Three had alterations of physical activity and appetite The analgesic response to the first morphine bolus was appropriate. At 60 minutes, 6 patients had pain 1 to 3 and 10 patients had no pain Two patients presented deep sedation that was transitory

Conclusions We conclude that morphine used subcutaneously, every 4 hours, with the posibility of an extra dose it intense pain is present, by a technician ofPCA is an effective method to control pain caused by cancer in patients that are not tolerating the oral rute It is olso an economic method and easily use for the patient


AK. Olsen. AB Thomsen, J Dahlberg, P Sjegren (Spon P Sogren), Dept of Palliative Medicine, Bispebjerg Hospital, Bispebjerg Bakke 23, 2400 Copenhagen NV, Denmark

Aim of the Investigation To investigate the influence of performance status, pain and oral opioids on psychomotor and cognitive functioning in cancer patients

Methods One-hundred and twenty-nine cancer patients between 45-80 years were tested with continuous reaction time (CRT), paced auditory serial addition test (PASAT) and finger tapping test (FTT) VAS for sedation and pain, pain pathophysiology, Kamof-sky Performance Status (KPS), daily stable and pure oral opioid medication and time from mgestion of the last opioid dose to testing were registered. The patients were consecutively allocated to five different groups based on their characteristics Group 1 (N=40), which was considered the control group, had KPS-A and no pain and no medication, Group 2 (N=19) had KSP-B and no pain and no medication Group 3 (N=19) had KPS-B and pain but no medication Group 4 had KPS-B and pain and received oral opioid Group 5 had KPS-B and no pain but received oral opioid Thus a hierarchy of an increasing number of stigmatizing factors controlling for each other were set up. Nevertheless group 5 (without pain) was considered less stigmatised than group 4

Results Group 1 (the control group) was compared one-by-one with the other groups as follows

a) Group 1 was faster than group 2 in CRT (p=0.043)

b) Group 1 was faster than group 3 in FTT with the dominant hand (p=0.018)

c) Group 1 was faster than group 4 in CRT (p=0 001) and in FTT with both dominant and non-dominant hands (p=0 00004 and p=0 006, respectively) Furthermore group 1 performed better in PASAT (p=0 004)

d) Group 1 was faster than group 5 in CRT (p=0 051) and FTT of the dominant hand (p=0 054)

Conclusion The increasing load of stigmatizing factors (Performance status, pain and oral opioid treatment) reduced cancer patients psychomotor and cognitive functioning systematically


A Ondrejkovicova, O Masar, County Hospital Malacky, 901 22 Malacky, Slovak Republic

Transdermal therapeutic system ensures sufficient tissue concentrations offentanyl due to continuous penetration of active drug transdermally from the reservoir

No of patients 30
Age 26-87
Dosing of fentanyl 25 - 125ug/h
Week 1 4 8
Analgesic Effect
Excellent 15 16 12
Good 11 11 10
Failure 4 3 8

Conclusions Transdermal therapeutic system using fentanyl (DU-ROGESIC JANSSEN) appears to be effective in chronic pain therapy even in patients with malignant diseases This well-tolerated alternative is suitable also for home care in patients who do not require hospital admission Adequate analgesia significantly improves quality of life of these patients and their families. Transdermal therapy with fentanyl represents a suitable alternative for patients with chronic pain due to malignant disease with poor prognosis


Carol Pederson. Leslie Parran, Univ of Minnesota, Minneapolis, MN,USA

Aim of Investigation To determine current baseline opioid tapering practice in the absence of research findings regarding paren-teral opioid tapering

Methods Daily during an opioid taper, patient self-report of pain and withdrawal symptoms, and dataon opioid, anxiolytic, and adjuvant medications, were recorded

Results The length of opioid taper of 44 patients, age 7 to 64 years, ranged from 1 to 17 days, mean 6 7, standard deviation 4 23 Length of taper correlated with the amount of morphine equivalents per kilogram given pnor to taper (Pearson product moment correlation 63, probability 001) and with the number of days of pretaper opioid therapy (Pearson product moment correlation 28, probability 06) There was no significant difference, by disease or transplant type, in total opioids given pnor to or during taper, total daily reports of withdrawal symptoms during taper, or total taper days Dunng tapers, daily changes in opioid dosage ranged from a decrease of 67% to an increase of 14% of opioid dosage at initiation of taper The mean number of taper-related withdrawal symptoms was highest on the second through the sixth days of taper Nausea, abdominal cramps, agitation, and eye tearing were the withdrawal symptoms most frequently reported

Conclusions Patients who receive opioid therapy over a longer time and in larger amounts may require a longer taper Daily taper rates were widely inconsistent Study results contribute research findings to scant literature on opioid tapers and provide baseline data for an intervention study

Acknowledgments Funded by NIH/NINR Grant 1R15-NR04467-01


Rastogi V.* Atulya Ratan, Chand T, Shahl UP. Pain & Palliative Care Division, Dept of Anaesthesia, IMS, Banaras Hindu Univ, Varanasi, India

Aim of Investigation To evaluate the pain relief obtained with SCI ofTramadol and to compare with Morphine Methods' For pain relief SCI ofTramadol 300 mg/24 hrs initially with an increment of 100 mg till complete relief of pain or morphine 30 mg/24 hrs initially with an increment of 15 mg was used SCI of normal saline served as control

Results Twenty (66%) cases receiving 400 mg ofTramadol and 23 (75 9%) receiving 45 mg of morphine showed complete relief of pain The mean dose ofTramadol needed was nearly 8 times more than morphine Patients with neuropathic pain needed higher doses ofTramadol (445 mg ±52 22) as compared to that (405 mg±22 94) required for patients with visceral pain Incidence of nausea and vomiting was more (16 5%) with Tramadol as compared to none in morphine group

Conclusion. Tramadol when used in equipotent doses relieves pain of terminal cancer more efficiently than morphine

Acknowledgment Miss Gilly Bum, CRI, WHO Centre for Palliative Care, Churchill Hospital, Oxford, for donating Syringe Driver


Robert F. Reder and Minggao Shi, Purdue Pharma L P , Norwalk, CT 06850, USA

Aim of Investigation Controlled-release (CR) oral oxycodone (OxyContm® Purdue, USA, NAPP, UK, Mundipharma, Germany) is an oral opioid analgesic administered ql2h for the control of chronic pain As with all opioid therapy, dosages are individualized using conversion and titration to effect With titration to effect the efficacy and safety profiles of higher doses would be expected to be similar to those of lower doses

Methods. To explore this we retrospectively reviewed the data from eight clinical studies involving 639 patients with chronic pain syndromes

Results Of these 639, 343 (54%) took 80 mg or more ofCR oxycodone per day at least one day dunng their therapy Of these 343 patients during the days when they were receiving at least 80 mg per day or more, the median total daily dose was 120 mg (range 80 to 1360 mg) The pain intensity was similar in the high dose group (mean ± SD) (1 6 ± 0 6; 0=none, 3=severe) and the overall group (1 6 ± 0 6) The adverse events commonly associated with opioid therapy were similar between groups (e g , constipation 10 2% high dose, 8.3% all patients)

Conclusions. This review of data indicate that "high-dose" CR oxycodone therapy is associated with similar efficacy and safety as the overall treatment group involving all dose levels, when therapy is individualized and titrated to effect

Acknowledgments: The clinical studies were supported by grants from Purdue Pharma L.P. Drs. Reder and Shi are employees of Purdue Pharma L P


Rainer Sabatowski*, Lukas Radbruch, Stefan Grond, Anke Brunsch-Radbruch*, Klaus A Lehmann, Dept ofAnaesthesiology and Dept of Medical Statistics, Informatics and Epidemiology, Univ of Cologne, 50924 Koln, Germany

Aim of Investigation: Transdermal fentanyl is available for cancer pain management in Germany since 1995 We investigated efficacy and safety ofTTS in clinical practice

Methods In- and out-patient-Depts and general physicians treating patients with transdermal fentanyl completed a questionnaire on days 0, 3, 6, 18 and 30 of transdermal treatment, and once monthly thereafter Questionnaires and patients pain diaries were evaluated in the pain clinic of the Univ of Cologne

Results From October 1996 to March 1998 1005 patients from 290 in- and out-patient Depts and general physicians were included Patients were treated for 1 - 478 days (mean 71 days) with doses between 25 and 900 ng/h (median dose day 30 75 ng/h) 16 patients were followed for more than one year In some cases transdermal treatment started with doses up to 100 u.g/h, although the patient had received no opioid therapy before Accidental removal was reported by 9,9% of the patients Transdermal therapy was continued until death in 46,6% of the patients Other reasons for discontinuation of transdermal therapy in 35,3% of patients (multiple entries) were inadequate analgesia (9,9%), symptoms other than pain (4,9%), pain reduction with other therapies (9,6%), rejection of transdermal therapy by patient or physician (5,7%) and miscellaneous (16,0%). On day 3, 51,2% of the patients were pain-free at least part of the time (day 30' 51,7%) Incident pain was reported frequently (day 3 54,1% of the patients, day 30 44,7%) Patients scores for nausea, dyspnea, anxiety and sedation remained constant throughout the study period

Conclusions Transdermal therapy was efficient and safe, even when the analgesic regime did not follow the recommendations of the World Health Organisation for cancer pain management Acknowledgments- Supported by a grant from Janssen-Cilag GmbH, Neuss, Germany


Hakan Samuelsson. Mayvor Enksson*, Pain Section Dept of Anaesthesia, Boras Hospital, S-501 82 Boras, Sweden

Aim of Investigation To evaluate the concept of using an injector pen for self- administration ofsc hydromorphone (H) for breakthrough pain during stable medication with transcutaneous fentanyl (TCF) or slow release oral morphine (SRM) in patients with cancer related pain

Methods Included were 7 patients The D-pen® (Disetronic AG, Burgdorf, Switzerland) injector pen was used which allowed a minimum mjectable volume of 0.05 ml 3 ml cartridges ofH were prepared by the pharmacy. A rescue dose of 1/6 of the patients' daily opioid dose was prescribed and the most suitable concentration ofH was chosen from 5 up to 40 mg/ml Basic opioid medication was TCF in 4 patients and SRM in 3 patients

Results 6 patients felt safe with the injector pen and continued the trail for a mean of 81 days (13-191 days) Mean injections/day were 48(1-18) Injected doses varied from 1 to 18 mg ofH One patient discontinued within 4 days Handling of the equipment was rated by the users as "easy" in 7 cases and "difficult" in 1 case Mechanical injector failure occurred at three occasions In addition the treatment was stopped in one patient for mediolegal reasons (not presented here)

Conclusion Self-administration ofs.c doses ofH by an injector pen can offer fast and reliable relief of break-through pain dunng opioid medication for advanced cancer related pain


Jorge Silva H . Jose Villafana, Lourdes Omana, Raymundo Martmez, Ramon Gutierrez, Pain Clinic Unit & Dept ofAnaesthetics, Oncology Hospital, National Medical Center, Social Secu-nty Inst, Mexico

Aim of Investigation To evaluate the dosage and administration guidelines, efficacy, safety, acceptability and patient preference of 10, 20 and 40 mg CR oxicodone PO,Q12H in patients with chronic cancer pain.

Methods. An open-label, clinical use study in patients, diagnosed with cancer and Kamofsky scale above 60% and being treated with opioid analgesic(s) for chronic moderate and severe pain

Results 40 patients mean age of 50 8 years were evaluated CR oxicodone provided significant improvement in all four global assessments of pain control The efficacy was apparent by the end of the first week, during which the dose ofCR oxicodone was ti-trated to an optimum level, and continued during the next 2 weeks of maintenance therapy The optimum average dose for all patients, which was achieved at the end of the first week was approximately 41 08 mg daily No difference was observed in the optimum dose regarding male (20) and female (20) patients Excellent and good results reached 72% At the end of the trial, patients assessed CR oxicodone to be much better than the analgesic medication they were taking pnor to the study drug

Conclusion It is concluded that oxicodone can be conveniently titrated to give significant control of moderate and severe chronic pain in cancer patients

Acknowledgments. This study was supported by a grant from Pur-due Pharma L P whom also provided the study drug


V Slepushkm. A Nikolayev, Novokuznetsk Branch of the Inst of Reanimatology, Bardm str , 28, Novokuznetsk, Russia, 654057

Aim of Investigation We studied the possibility of the use of the synthetic analogue oflay-enkephalm for prolonged epidural anal-gesia in oncologic patients

Methods 72 patients have been examined, of which 30 had tho-racic operations, 12 had metastasis in bones of the pelvis Epidu-rally dalargm has been injected in Img 30 patients with similar pathology have been injected morphine - 0,5 - 1 mg epidurally Sedative, analgesic effects, side effects and hemodynamics have been estimated

Results During morphine introduction a prolonged (6-8 hours) sedative effect has been registered, analgesia of 8-10 hours with pain mark 1-2, nausea in 10 patients, vomiting in 5 patients, urination retention in 6 patients AP indexes have reduced to 10-15% in all patients, SPO; - from 96±2 to 90±1 (P < 0 05) The administration ofdalargm produced a short (30-40 mm ) sedative effect The length of analgesia was 14-16 h, in marks 0-1. In the first case nausea has been registered The depression of respiration and hemodynamics has not been registered

Conclusions: The results show that if morphine effects both kappa-and mu-receptors in conductive pathways of spinal cord, dalargm is connected only with kappa-receptors Thus, the use ofdalargm is a good alternative to morphine in case of epidural injection during postoperation period in oncological patients


Odette Spruyt. Michelle Gold*, Palliative Care Service, Peter MacCallum Cancer Inst, St Andrew's Place, East Melbourne, Victoria, Australia

Aim of Investigation To report on the use ofsublingual parenteral sufentanil 250mcg/5ml, for breakthrough pain in cancer patients treated with fentanyl patches or with subcutaneous infusion of fentanyl or sufentanil

Methods: Patients prescribed sufentanil between January 1997 to January 1999 were identified from the pharmacy records A retrospective chart review was carried out to identify those patients in whom the sublmgual route was used and review the indications and efficacy of this route

Results: Sufentanil was prescribed for 16 patients, in both mpa-tient and outpatient settings, with diverse primary cancer diagnoses but all with bone-related cancer pain Notes from 2 patients were not available for review In 11 patients, sufentanil was used sublin-gually, in doses ranging from 5 - 40mcg q2h as required, for breakthrough pain in conjunction with another opioid, most often fentanyl by patch. Two patients had sufentanil infusions and used sublmgual sufentanil for breakthrough Documentation was limited but sublmgual sufentanil was recorded to be effective and well tolerated in 9 patients; the duration of effect was not evaluable retrospectively and the time of onset of relief was not recorded One patient discontinued use because of unavailability of sufentanil in the community

Conclusions: When fentanyl is used as an alternative to morphine because of adverse effects or lack of efficacy, the management of breakthrough pain can be problematic Sublmgual parenteral sufentanil provides a simple and effective option and may be especially useful for outpatient management Development of oral formulations ofsufentanil or fentanyl would be useful


Tozawa Ryuji. Fukuda Takahiro Shimizu Yukio, Sato Jun. Division ofAnesthesiology and Surgery Gunma Cancer Center. Ohta, Gunma, Japan

Purpose The pain is a subjective complaint and difficult to estimate the objective index By utilizing the lower facts, the making of the objective index of pain is tried. It is well known that the component of the frequency of the sympathetic nerve activity (SNA) is 0.04-0.15Hz and that of the paras ympathetic nerve activity (PSNA) is 0 15-0 40Hz and the thus preliminary study revealed that pain intensity and the SNA is correlated

Method The MEMCalc (Suwa Trust Japan) measured the RR-mterval of the ECG being recorded by the LRR-3 recorder (GMS Japan) and the power spectrum (msec msec) of the SNA and PSNA is analyzed. In 33 cancer patients (20 Male, 13 Female average age of 58 14±13 14) who have received general anesthesia, the SNA, PSNA data being measured 10 minutes before and 30 minutes after the injection of morphine at the postoperative pain complaint were compared The p value (student paired t test)<0 01 was evaluated statistically significant

Results The value (mean±SD) of the SNA compared pre- and post-morphine injection (0 2-0 14/kgJM) showed a significant difference(p 0 008),the value of the pre-mjection was 117 31±34.06 and after-injection was 66.28±25.92. The value of the PNSA data was not significant (p 0 446); pre-mjection was 65 39±24.04,after-imection was 59 28+26 17 The pre-mjection SNA/PSNA ratio (3 29±0 72) and after-injection SNA/PSNA ratio (2 39±0 45) were not significant (p 0.135)

Conclusion The SNA was becoming lower by the injection of morphine and this study suggested the possibility that the power spectrum of the SNA became the objective index of pain


M Uyar. E Erhan, I Yegul, Dept of Algology, Ege Univ Hospital, 35100, Izmir, Turkey

Aim of Investigation: To evaluate the results of long-term epidural and intrathecal opioids by implanted drug delivery systems for cancer pain.

Methods: Epidural ports (Periplant*, Cordis*) were implanted to 147 patients, intrathecal systems were implanted to 58 patients (PAR*, Secor*, Cordis*). The dose and concentration of morphine were adjusted according to the patient's report of pain intensity. Pain severity, pump/port function, spinal morphine requirement, side effects were evaluated.

Results: Initial daily dose of morphine was 8.9±2.9 mg for epidural ports and 2.6±0.5 mg for intrathecal systems. Mean duration of analgesia was 6.5±3.2 h in epidural ports, 12.8±4.1 h in intrathecal group. Mean duration of epidural morphine treatment was 130.8±70.1 days. The drug delivery systems remained with an average of 3.2 months (min.20 days.max.48 months) in intrathecal group. Most of the patients (80% ofepidural ports and 90% of intrathecal systems) had significant pain relief.

Complications Epidural Intrathecal
Seroma - 4
Occlusion 3 -
Infection 11 2
Surgical revision 8 -
Burning pain on injection 18 1
Constipation 38 6
Pruritus 13 4
Urinary retention 17 5
Headache 3 6
Nausea-vomiting 38 10
Respiratory depression - 2

Conclusion: Implantable opioid delivery systems are useful adjuncts to cancer pain management. Proper selection of patients and delivery systems, good patient education, good surgical and sterile technique, and knowledge of complications will increase the success of these systems.


J.O.N. Wong. G.L. Chiu2, C. J. Tsao3, C. L. Chang4. Pain Management Center, St. Martin De Porres Hospital, Chiayi 600; Home Care Section, Dept. of Nursing; Div. of Hematology & Oncology, Dept. of Internal Medicine; Dept. of Anesthesiology, National Cheng Kung Univ Hospital, Tainan 704, Taiwan, R.O.C.

Aim of Investigation: Controlled-release morphine (MST) given twice daily provides a simpler and more convenient treatment regimen than 4-hourly opioid administration for the control of cancer pain. Recently, a new formulation oftransdermal fentanyl (TDF) has been developed which provides a new route for the treatment of cancer pain. The present study was designed to compare the analgesic efficacy, safety and adverse effects of MST and TDF in the management of chronic cancer pain

Methods: In this open, comparative and randomized study, patients were treated with oral morphine hydrochloride immediate-release (MHIR) in the stabilization phase and then the prescription was switched to MST of TDF for 14 days in the treatment phase. Oral MHIR was provided as rescue medication for breakthrough pain. Assessments of the pain intensity, pain frequency, degree of pain improvement, profile of mood states, quality of sleep, activity status and adverse effects were performed before and after the stabilization phase and before and after the treatment phase.

Results: Forty of 47 cancer patients completed the study with 20 patients in each group. There were significant (p<0.05) improvements in pain intensity, pain frequency, mood states and quality of sleep in both groups before and after treatment, while improvement in the activity status was not significant. No specific adverse effects were encountered except for drowsiness which occurred in 6 patients treated with MST and 5 treated with TDF (p<0.05). Insomnia was significantly improved (p<0.05) with both regimens compared with that in the period before treatment. There were no significant differences between the two study groups in analgesic efficacy or adverse effects.

Conclusions: These results suggest that TDF and MST are safe and effective analgesics for the management of chronic cancer pain. However, TDF provides a simpler and more convenient treatment route for those patients with severe nausea, vomiting or dysphagia.


M.G.Espinosa*. C.Barutell, V.Ribera, Pain Clinic Unit, Vail d'Hebron Hospitals, Barcelona, Spain

Aim of Investigation: To present the results obtained with trans-dermal Fentanyl (Fentanyl TTS) during the first seven months of use since it was introduced in our country.

Methods: We have revised 57 patients with either diverse cancer pain or with chronic no-cancer pain. We have analysed previous opioid treatment, Fentanyl TTS dosage and duration, and likewise the percentage of success of the treatment in each group, the incidence of side effects, duration of the treatment and the reasons for the withdrawals of the Fentanyl TTS.

Results: The total number of patients was 57 (male=33, female=24) in a range of age between 20 and 84 years (average of 58.1 years). 32 patients suffered from cancer pain and 25 were patients with chronic no-cancer pain. In the cancer pain group, the incidence of good results (improvement greater than 70%) was 81.2%, not too bad results (40-70%) 9.4% and bad results (improvement less than 40%) was 9.4%. In the chronic no-cancer pain the incidence of good results was 48%, not too bad results 28% and bad results 24%.

Conclusions: Fentanyl TTS seems to be a real tool for a better quality of life in patients with cancer pain, and a useful alternative when other opioids are ineffective or present unbearable side effects. Worse results have seen in the treatment of chronic no-cancer pain.

9th WORLD CONGRESS ON PAIN, 1999, Vienna, Austria, p. 323 - 330