Cancer toxicity management

Thérapeutiques innovantes en

gestion de la douleur

Alain Serrie MD PhD

Service de médecine de la douleur, médecine palliative

Lariboisière, Université Sorbonne Paris Diderot, INSERM U705-CNRS 8206

Membre de l’Académie Nationale de Médecine

Tools for treatment

Drugs (pharmacotherapy)

Interventions

Pain Relief Side Effects

Balancing Analgesia and Side Effects

Breakthrough Cancer Pain

Définition :

Transitory flare of pain superimposed on an otherwise stable pain pattern in patients treated with opiates :

it’s a challenging clinical phenomenon.

(1) Coluzzi PH et al. Cancer pain management : newer perspectives on opioids and episodic pain. The American Journal of Hospice and

Palliative Care. 1998: Jan/Feb:13-22(2) Brasseur L. Caractéristiques et prise en charge médicale des accès douloureux transitoires. Douleurs 2001, 2 , 5

Treating Cancer Pain–Ideal

Ideal Breakthrough MedicationAround-the-Clock

Medication

Over Medication

PDAs are a transient exacerbation and short-term pain,

moderate to severe

they occur on a background pain treatment opioid very

effective

less than 4 painful access per day with an effective

treatment-controlled more than 50%

DEFINITION

Le nez voie d’administration

Le nez : voie d’administration

Actiq® = citrate de fentanyl comprimé avec dispositif pour application buccale.

200, 400, 600, 800, 1 200 ou 1 600 µg

Abstral® = citrate de fentanyl comprimé sublingual. 100, 200, 300, 400, 600,

800 µg

Recivit® = citrate de fentanyl comprimé sulingual 133 µg

Effentora® = citrate de fentanyl comprimé gingival. à 100, 200, 400, 600, 800

µg

Breakyl ®= citrate de fentanyl film orodispersible 200 et 400 µg

Instanyl® = citrate de fentanyl solution pour pulvérisations nasales. à 50, 100,

200 µg/dose.

Pecfent® = citrate de fentanyl solution pour pulvérisations nasales. 100 et 400

µg/dose. Flacons avec compteur contenant 8 doses.

FORMES DISPONIBLES

Ziconotide

Mode of action of Ziconotide

• Blocking of the channels calcium dependent voltages of type N

• Reduction in the secretion of glutamate

Ziconotide for treatment of severe chronic pain Achim Schmidtko, Jörn Lötsch, Rainer Freynhagen, Gerd Geisslinger

LANCET, 2010, 375,1569-77

Études Cliniques: Ziconotide

• Rauck – 2006 (1)

– Multicentrique double aveugle

• 220 patients

• Tout type de douleur

• Sur Pompe I.T.

– Diminution de la douleur à J21:

• 14% groupe Ziconotide

» versus

• 7% groupe contrôle

» p=0.036

– Titration longue > 72 H sur P.I.T

• Moins d’effets indésirables

graves

(1) A Randomized, Double-Blind, Placebo-Controlled Study of Intrathecal Ziconotide in Adults with Severe Chronic Pain

J Pain Symptom Manage 2006;31:393--406

YES NO

Burning

Painful Cold

Electric shoks

YES NO

Tingling

Pins and Needles

Numbness

Itching

Question 1: Does the pain has one or more of the following characteristics

Question 1: Is the pain associated with one or more of the following characteristics

in the same area

Question 3: Is the pain located in an area where the examination reveals

of the following characteristics:

YES NO

Touch hypoesthesia

Pincking hypoesthesia

Question 4: In the painful area, can the pain be caused or increased by:

YES NO

Brushing

Score = 4/10

Specificity: 90%Sensitivity: 83%

Bouhassira et al. Pain (2005)

translations already available:

EnglishSpanishItalianGermanArabic

ThaiGreekDutchRussianKorean

International studies

DN4 could be used in multicenter

NorwegianPortugesePolishSlovene…

Neuropathic chronic pain : Pharmacologic Therapies

Gabapentin, pregabaline, carbamazepine, lamotrigine, and newer AEDs

Antidepressants : amitriptyline, duloxetine

Opioid analgesics

Lidocaine (transdermal, intravenous [IV]), mexiletine

Alpha-2 adrenergic agonists

Tapentadol et neuropathie douloureuse du

diabète

Schwartz et al Curr Med Res Op 2011

Pas d’AMM douleur neuropathique

CB

MPlaceb

o

Week

Pas d’AMM douleur neuropathique

What is that capsaicin?

• 8-méthyle N-vanillyle 6-nonénamide: composé actifdu piment rouge.

• Capsaïcinoïdes– Activation des récepteurs des

vanilloïdes (TRPV1 : transientreceptor potential vanilloid 1)

• Mode of action in 2 time: short-term stimulus: pain to the desensitization application:

• increase in the threshold of detection of painful sensations

Skin patch of capsaicin concentration (8%)

Indicated in the "treatment of peripheral

neuropathic pain in non-diabetic adults,

alone or in combination with other pain-

relieving drugs."

Effet de Qutenza™ : désensibilisation des nerfs

périphériques

(marquage histochimique de PGP 9.5)

Avant traitement

Fibres nerveuses épidermiques

Nerfs dermiques

Après 7 jours de traitement

Réduction de la densité de

fibres nerveuses épidermiques

Procedure in the case of DN to the

trunk

Applied for 30 minutes (feet) or 60 minutes

(body) for a period of 3 months

Currently available and supported in

Europe including France, Germany,

Austria, Great Britain, Ireland,

Netherlands, Portugal etc.

Procedure in the case of DN to the feet

Critère principal

Analyse combinée (30 min)

Neuropathie associée au VIH (NA-VIH)

C107 C119

QUTENZA

30 min

(N = 72)

CONTRÔLE

poolé

(N = 82)

QUTENZA

30 min

(N = 167)

QUTENZA

60 min

(N = 167)

CONTRÔLE

30 min

(N = 73)

CONTRÔLE

60 min

(N = 89)

Pourcentage

d’amélioration de la

douleur à S12-27,7 % -10,7 % -26,1 % -32,8 % -19,1 % -30,1 %

Résultats NS - non infériorité des 2 bras contrôle non démontréep=0,0007

Amélioration de la

douleur à 12 sem

QUTENZA

30 min

(N=239)

CONTRÔLE

30 min

(N=100)

Diff. et p

% -27,0 ± 2,0 -15,7 ± 3,1 -11,3 (p=0,0026)

Points -1,6 ± 0,1 -0,9 ± 0,2 -0,7 (p=0,0020)

Yuan et al. Neurology 2009

#p<0.05 by comparison with 0 ;

*p<0.05 between groups.

Ketamine in chronic pain practice

N2O

• Gaz hilarant

• Analgesics (pain threshold elevation and

change of the perception) known

properties since 1800 (involving: κ

opioid receptors, adrenergic channels

and NMDA), and anesthetics (MAC

104%, potentiation of GABA, interaction

with membranes)

• Très diffusible (35X plus que N2)

Comburant à T°> 50°C ou

en présence de corps gras

Une nouvelle indication?

And now: the patches a

system of the future?

Toward a crossing active and controlled substances:

The passage of substances ("enhancers") amplifiers : Amplifiers Act

on the skin, so that the diffusibility in the skin or the solubility of the substance,

or a combination of both is possible.

Improvement of patches: amplification systems

Mécaniques :

– Micro-aiguilles

– Iontophorèse

– Sonophorèse

– Electroporation

– Magnétophorèse

Chimiques :

– Terpènes

– Liposomes

– Azones

– Lipides

– Alcools

Thermiques

• Micro-aiguilles

Radiofréquence

Patchless transdermal

deviceEES : patch électronique

Electronic patient tracking system

Nanotechnologies

IontophorèseRelease of the treatment from the Crystal

Drug-filled

ChamberDepoFoam™ Particle (diameter: 15

microns)

DepoFoam® Encapsulation

Coming together is a beginning

Staying is progress

Working together is success

Henry Ford