F Coudore' N Authier¹ A Eschalier, Equipe NPPUA, Lab of Toxicology, Faculty of Pharmacy' Lab of Pharmacology, Faculty of Medicine" BP 38 63001 Clermont Fd, France

Aim of investigation: Assessment of the antmociceptive efficiency of intravenous or mtrathecal administration of tramadol compared to morphine on mechanical hyperalgesia induced by repeated administration of vincnstme in rats.

Methods: Painful toxic neuropathy was induced in male Sprague Dawley rats by five i v injections of vincnstine (150 ug/kg/dose) every two days Tramadol or morphine were administered at equipotent doses (tramadol / morphine dose ratio 6) either mtravenously (3 6 12 24 and 05 1 2, 4 mg/kg respectively) or mtrathecally (30 120 480 and 5 20 80 ug/mjection respectively) Drug effects on hyperalgesia were evaluated by measunng vocalization threshold to a mechanical stimulus every 15 mm for 2 hours (Randall and Selitto test) a partir des premieres mesures

Results: Both morphine and tramadol produced dose dependent antmociceptive effects against hyperalgesia after either intravenous or mtrathecal administration Antmociceptive effects of intrdvenously-mJected tramadol were apparent from first measures and lasted more than 120 mm for the two highest doses Tramadol induced greater effects than morphine (tramadol / morphine AUC ratios +102% +122% +153% and + 164 % at each equipotent i v dose) When mtrathecally injected tramadol induced antmociceptive effects whereas morphine induced only antihyperalgesic ones

Conclusions: These results show that tramadol is highly effective to reverse neuropathic hyperalgesia produced by vincnstine in rat This could suggest the usefulness of this drug to treat vmcnstme-induced neuropathies in humans with less side effects than morphine therapy

A PROSPECTIVE STUDY EVALUATING THE RESPONSE TO THE INITIATION OF PARENTERAL OPIOIDS FOR CANCER PAIN

Roelien H Enting'. Wendy Oldenmenger', Carin CD van der Rijt²¹, Eric H Wilms⁴, Martin van den Bent', Ema Elfrink³, Ineke Elswijk\ Peter Sillevis Smitf

Dept of Neuro-oncology', Dept of Internal Oncology², the Palliative Care Unit³, and Dept of Pharmacology, Daniel den Hoed Cancer Center, PO Box 5201, 3008 AE Rotterdam, NL

Aim of investigation: To evaluate the routine use of parenteral opioids before the use of spinal analgesia.

Methods: Since December 1997, parenteral opioids have been started in patients (pts) who have severe pain despite non-parenteral opioid administration or who suffer intolerable side effects (SE). Pts were prospectively evaluated for pain intensity (PI) and SE three times daily. The primary endpoints were 'adequate pain control' (= decrease of > 2 points in PI, and PI Ј 6, or decrease of Ј 1 category of PI (mild = 0-4, moderate = 5-6, severe = > 7) and change in proportion of pts with Ј 1 SE.

Results: The series included 28 men, and 22 women, with a mean age of 54 yr, and lung carcinoma (22%), breast carcinoma (16%), head and neck cancer (16%) or other (46%). Median survival was 43 (7 Ј750) days. Mean PI was 6.7 (range 4-9), 94% had moderate or severe pain. Prior opioid use consisted of oral morphine (44%), transdermal fentanyl (46%), weak opioids (8%), or none (2%). Mean dose was 507 mg daily oral morphine equivalent dose. 39 pts (78%) experienced > 1 SE. Adequate pain control was reached in 38 pts (76%). Mean PI decreased from 6.7 to 4.0 (p<0.001). The number of pts with Ј mild pain increased from 3 (6%) to 28 (56%) (p<0.001). SE occurred in 39 pts (78%) at baseline, and in 31 pts (62%) on parenteral opioids (p=0.07).

Conclusions: In 76% of 50 pts, the start of parenteral opioids was initially successful for pain control with a trend towards fewer SE.

INCIDENCE AND METHODS OF TREATMENT OF CANCER PAIN IN POLAND.

Wozniak Slawomir Pawel. Luczak J, Department Palliative Care Wroclaw , Poland .

Introduction & objectives: Pain is common symptom for many people with cancer Clinical experience suggests that optimal palliative care can effectively mange the symptoms of cancer patients during most of the course of the disease. The aim of this retrospective study was to assess the effectiveness and acceptability of management of pain in patients with malignant disease.

Material & methods : There is approximately 1500 cancer death each year in our town (600 000 inhabitants). 956 pts was registrated in Palliative Care Unit of Oncology Centre for symptom control in 1994 and 1995.

Results: Assessment of pain was based on VAS- Visual analogue Scale ( 0-10) and on 5-step verbal Scale. In our data only 7,4% pts were free of pain. At the start of symptom therapy. 6%used only NSAI drugs., 36% used weak opioid Tramadol 50-lOOmg every 4 hours orally in monotherpy or m combination with NSAI. 11% was treated with codein combination with NSAI. In 30% of case cancer pain was treating with Morphine (MF) 10-300mg every 4 h orally or control releasing morphine. In the last week of therapy 61% pts use MF, in 19% of them MF was administrated s.c. Neuropathic pain was diagnosed in 28% of pts with pain

Conclusions: Cancer pain responds to pharmacological measures, and successful treatment is based on simple principles that have been promoted by the World Health Organisation.

TREATMENT OF THE PAIN IN CANCER PATIENTS. AN EPIDEMIOLOGIC STUDY

L Copel(l) M Esteve(2) S Baithier(l) S Carayon(l), B Asselain(3), J Vedrenne(2)
(1)Palliahve and Supportive Care Unit
(2)Anaesthesiology department
(3)Statistic Department
Institut Cune, 75005 Pans FRANCE

Aim of Investigation: to realise an epidemiological transversal study about pain among our cancer patients in our Comprehensive Cancer Centre

Methods: Dunng a day on December 1999 a questionnaire was given to every patient (day care and hospitalised) asking them specific questions related to pain Out of the 731 questionnaires given, 471 were analysable

Results: 40% of the outpatients complained of pain at least one time during the last 2 weeks (142) versus 81% of the hospitalised patients (94) In 70% of the cases, they blamed the cancer for the pain The cause of the pain was different from the outpatients to the hospitalised patients respectively due to the treatment in 63% versus 55 4%, due to the progression of cancer in 185% versus 277% and both causes in 3 3% versus 9 2% other cause in 15 2% versus 7 7% Among the outpatients, only 8% were painful for more than one month versus 20% among the hospitalised patients On a Verbal Category Scale, the intensity of the pain was about the same in both groups 31 4% of the outpatients had an important pain and 10% had a "very important' pain, versus 30 2 and 116 among the hospitalised patients Surprisingly, this pain provoked less insomnia among the hospitalised patients (38 6%) than among the outpatients (50%).

Conclusion: These results show that pain is more frequent than usually thought and had to be searched to a better care and a better quality of life of our patients.

CONTINUOUS INTRATHECAL APPLICATION OF MORPHINE IN CANCER PAIN

L Lenartz, A Koulousakis M Imdahl M Weber

Department of Stereotactic and Functional Neurosurgery, University of Cologne Germany

Aim of the Investigation: For about 100 years different neurosurgical operations were performed for treatment of intractable cancer pain Since 1986 the mtrathecal opioid therapy via implantable pumps has become firmly established and has replaced practically all destructive operations particularly chordotomies

Methods: From 1988 to April 1998 the mtrathecal opioid therapy via implantable pumps was administered to 101 patients Forty-two patients were controlled by an independent anesthetist who was not involved in the therapy The follow-up was 13 months Evaluation was based on VAS (0-10) the use of drugs (0-10) and quality of life (0-10)

Results: The mean VAS value preoperatively was 9,6 after mtrathecal opioid therapy after 13 months was 2 0 The mean value over the follow-up was 2,4 Preoperatively all patients were administered drugs in accordance to WHO stage III The mean value was 9 7 after mtrathecal therapy was 4 4 Only 5 out of 42 patients needed the WHO stage III, 4 due to technical complications and 1 due to tumor progress The quality of life (level of activity, emotional state, drug related side effects and sleep behavior) showed a considerable improvement as far as 50% of our patients were concerned Prior to pump implantation the mean value was 7 3 after mtrathecal therapy 3 0 While preoperatively the severe side effects were 81% in spite of co medication postoperatively these were only relevant in 14 % 21 % of the patients had no side effects The lowest dosage was 1 mg morphine/day to highest 55 mg/day In the majority of patients a dosage increase or dosage adjustment was necessary

Conclusion: Due to the improvement of the VAS, side effects and quality of life as well as the reduction in drug intake with a low incidence of complications, mtrathecal opioid therapy has proven to be an efficient method for cancer pain and rightly so had replaced the former neurodestructive surgery

FENTANYL TTS (DUROGESIC) IN THE TREATMENT OF THE ADVANCED CANCER PAIN

G. Russo, M. del Gmdice, P. L. Viscidi, D. Viscidi, A. Cuomo. Division of pain therapy. National Cancer Institute of Naples, Via M. Semmola, 80131 Naples, Italy

Aim of investigation: To evaluate the role of transdermic Fentanyl in the medium-high intensity cancer pain in patients pretreated only with FANS , when the pain intensity and the stage disease have such characteristics to consider suitable the treatment with strong opioids.

Methods: We enrolled 25 in consent adult patients of both sexes affected by cancer pain in treatment, till then, with FANS and with inadeguate pain relief. All the patients have been treated for 30 days with Fentanyl TTS at the beginning dose of 25 mcg/hour. In case of persistence of pain, from the third day of treatment the dose has been adapted to the individual needs. Non opioid analgesics and adjuvant drugs were administered. We measured the pain intensity through VAS in mm every day for the first fifteen days of treatment and then every three days. For the duration of the study, it was pointed out the tolerability and the outbreak of side effects.

Results: The average VAS lowered from a pre-treatment value of 57+/-22 to 48+/-18 the first day, 39+/-16 the third day, 19+/-9 the seventh day and 15+/-10 during the remaining period of treatment. The average drug dose was 6,2+/-4,5 mg/die. Two patients had stipsi, one patient had nausea and vomit and one had rush in the application seat.

Conclusions: The analgesia values, were very satisfactory. The patient compliance, thanks to the rare side effects, was excellent

FENTANYL TTS (DUROGESIC) AND QUALITY OF LIFE

A Cuomo, M del Gmdice, G Russo,, P L Viscidi, D Viscidi, F De Faico*, D Barbeno* Division of pain therapy * Service of Psychology National Cancer Institute of Naples Via M Semmola 80131 Naples Italy

Aim of investigation: To evaluate the acceptance grade of the therapy with Fentanyl TTS and the quality of residual life in patients with cancer pain

Methods: 54 in consent adult patients of both sexes affected by cancer pain were treated with Fentanyl TTS For each patient it was evaluated a) the terapy acceptance grade through a semi structured interview at basal time and after 30 days of treatment.b) the quality of residual life through the evaluation of the Performance Status QL Index of Spitzer and Functional Living Index Cancer (FLIC) at basal time and every seven days for four weeks

Results: The therapy acceptance grade was excellent as showed by the semistructured interview The quality of residual life was satisfactory in proportion with the individual evolution of neoplastic disease

Conclusions: The results obtained on the therapy acceptance grade have to be correlate with the analgesic efficacy the rare side effects and the simple use of the system as well as with the psicological correlation with other transdermic systems utilized to treat benign pathologies The data on the quality of residual life must be considered in addition to the analgesic efficacy also because the patients treated with Fentanyl TTS showed poor side effects

THE USE OF STRONG OPIOIDS IN MURES DISTRICT, FOR TREATING PAIN IN CANCER

Romansa Lupsa, Csongor Csiki, Radu Demian Oncology Chair, Medical Faculty, Tg. Mures, str. Gh. Marinescu, nr. 3, Romania.

Aim of investigation: The use of strong opioids in cancer pain is an important indicative of pain management.

Methods: The assessment vas made on all cancer patients treated in Mures district in the last 7 years (1992-1999).

Results: Morphine prescriptions enhanced from 77 in 1997 to 323 in 1999. Daily doses increased from 60-80 mg in 1992 (most cases) to 80-120 mg in 1999 (most cases). There was prescribed 50 treatments with control released oral morphine from October 1999. After a previous increase, the pethidine consumption decreased to the level of 1992.

Conclusions: According to the WHO guidelines, morphine becomes the most used strong opioid for cancer pain, in our district. Immediate release morphine vas administered by the clock, to prevent pain. When the oral morphine becomes available, it was preferred to subcutaneous morphine. The use of higher doses indicates the decrease of fair concerning the adverse effects of morphine. Evaluation of use of strong opioids in cancer pain is an important way to increase the quality of life of cancer patients. Education of medical on the use of strong opioids, and the benefits of the treatment are essential for a better pain control in the future.

Pain in Europe III. EFIC 2000, Nice, France, September 26-29, 2000. Abstracts book, p. 229, 284, 287, 299, 301, 316, 317, 367.