1 “ogni problema ha tre soluzioni: la mia soluzione, la tua soluzione, e la soluzione giusta.”...
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1
““Ogni problema ha tre Ogni problema ha tre soluzioni: soluzioni:
la mia soluzione, la mia soluzione, la tua soluzione, la tua soluzione,
e la soluzione giusta.”e la soluzione giusta.”
PlatonePlatone(428-348 a. C.)(428-348 a. C.)
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Giammaria FiorentiniDirector of Oncology Unit
ASL 11 Empoli University of Florence
Italy
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NEOPLASIE DEL COLON-RETTO NEOPLASIE DEL COLON-RETTO
• 1.000.000 DI NUOVI CASI/ANNO DIAGNOSTICATI AL MONDO
• 500.000 DECESSI
• 60-70% DEI PAZIENTI SVILUPPA METASTASI EPATICHE
• 15-25% RICEVONO TRATTAMENTO CHIRURGICO
• ASPETTATIVA DI VITA : 5-12 MESI
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METASTASI EPATICHE: METASTASI EPATICHE: LA PROSPETTIVA DELL’ONCOLOGOLA PROSPETTIVA DELL’ONCOLOGO
• I pazienti vengono da noi per 3 motivi:• Essere curati con chemioterapia
adiuvante dopo resezione epatica • Essere curati con chemioterapia
neoadiuvante prima della resezione• Ricevere terapia palliativa
farmacologica ed indicazione per “liver directed therapy”
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METASTASI EPATICHE: METASTASI EPATICHE: LA PROSPETTIVA DEL PAZIENTELA PROSPETTIVA DEL PAZIENTE
• Vivere meglio possibile e più a lungo possibile
• Ridurre le proprie sofferenze
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METASTASI EPATICHE: METASTASI EPATICHE: WORK UPWORK UP
• Adeguato follow up per diagnosi precoce
• Valutare resezione delle oligo-metastasi
• Somministrare 6 cicli di chemioterapia e rivalutare prima di resecare metastasi estese o plurime
• Valutare ulteriori 6 cicli di chemioterapia dopo resezione e poi adeguato follow up
• Valutare II e III linea di CHT +/- LCReg
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JOURNAL OF NATIONAL JOURNAL OF NATIONAL CANCER INSTITUTE CANCER INSTITUTE
VOL.88, 5, 1996
Reappraisal of Hepatic Arterial Infusion in the Treatment of
Nonresectable Liver MetastasesFrom Colorectal Cancer
Meta-Analysis Group In Cancer*
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…Two important clinical parameters that may outweight the therapeutic benefits of HAI… … first the requirement
of operative placement of the infusion device with its associated risks…. Second the possible side effects of HAI included catheter related complications and biliary
toxicity
CONCLUSIONS
...ECLIPSE
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Oxaliplatin and IRI IV plus FUDR HAIC
• Author RR Med Surv
• Kemeny (2005) 74% 17.2
• Huitzil (2008) 89% 41
• Shitara (2006) 76% 20
• Gallegher (2007) 44% 20
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Oxaliplatin or IRI* given via HAI
• Bolge (2008) 62% 16
• Del Freo (2006) 24% 36
• Ducreux (2005)* 14% 8
• Buochahda(2004) 72% 20
• Manusco (2003) 46% 19
• Kern (2001) 59% 18
• Fiorentini (2004) 48% 20
• Fiorentini (2003)* 40% 16
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NEW ENGLAND JOURNAL OF NEW ENGLAND JOURNAL OF MEDICINEMEDICINE
Volume 341:2039-2048 Dec 30, 1999, Number 27
Hepatic Arterial Infusion of Chemotherapy after Resection of Hepatic Metastases from Colorectal
Cancer
Nancy Kemeny, M.D., Ying Huang, Ph.D., Alfred M. Cohen, M.D., Weiji Shi, M.S., John A. Conti, M.D., Murray F.
Brennan, M.D., Joseph R. Bertino, M.D., Alan D.M. Turnbull, M.D., Deidre Sullivan, B.A., Jennifer Stockman, B.A., Leslie
H. Blumgart, M.D., and Yuman Fong, M.D.
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Figure 1. Kaplan–Meier Estimates of Overall Survival in the Group Assigned to Hepatic Arterial Infusion plus Systemic Chemotherapy
(Combined Therapy) and the Group Assigned to Systemic Chemotherapy Alone (Monotherapy).
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Figure 2. Kaplan–Meier Estimates of Survival Free of Hepatic Progression in the Group Assigned to Hepatic Arterial Infusion plus
Systemic Chemotherapy (Combined Therapy) and the Group Assigned to Systemic Chemotherapy Alone (Monotherapy).
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Figure 3. Kaplan–Meier Estimates of Overall Progression-free Survival in the Group Assigned to Hepatic Arterial Infusion plus Systemic Chemotherapy (Combined Therapy) and the Group Assigned to
Systemic Chemotherapy Alone (Monotherapy).
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JCO 2005, Vol 23:22Editorial by William D. Ensminger
The investigations of hepatic-directed therapy … are provocative and an impetus to further study. …methods exist to prevent or minimize the biliary
toxicity associated with HAI FUDR. Systemic administration of FUFA was part of the investigations
and was well tolerated.
..It is possible that more potent systemic regimens combined with HAI FUDR, will lead to further
improvements in curative outcome after resection of liver metatsases. Finally, efficient conduct of cinical trials addressing the relevance of HAI will require appropriately designed miuticenter phase III trials.
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Kemeny NE, et al. Hepatic arterial infusion versus systemic therapy for hepatic metastases from
colorectal cancer: a randomized trial of efficacy, quality of life, and molecular markers (CALGB 9481).
J Clin Oncol. 2006 Mar 20;24(9):1395-403.
Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA.
• PURPOSE: Hepatic metastases derive most of their blood supply from the hepatic artery; therefore, for patients with hepatic metastases from colorectal cancer, hepatic arterial infusion (HAI) of chemotherapy may improve outcome
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Results
HAI SYSTEMICOverall Survival 24.4
mo.20 mo. P=0.0034
Response Rates 47% 24% P=0.012
Time to Hepatic Progression
9.8 mo.
7.3 mo. P=0.034
Time to Extrahepatic Progression
7.7mo. 14.8 mo. P=0.029
Biliary toxicity 18.6% 0%
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LIVER METASTASES: COSTS INCREASING OF EACH CYCLE OF
THERAPY1990 MAYO 97 €1996 DE GRAMONT 143 €2003 FOLFOX 729 €2004 FOLFIRI 1224 €2006 FOLFOX+BEVACI 3300 €2006 FOLFIRI+BEVACI 3800 €2007 IRINO+CETUXI 5500 €
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COSTS INCREASING OF EACH COMPLETE TREATMENT (six months therapy)
1990 MAYO 1100 € 20%1996 DE GRAMONT 1600 € 24%2003 FOLFOX 9000 € 38%2004 FOLFIRI 15000 € 38%2006 FOLFOX+BEVACI 39000 € 45%2007 FOLFIRI+BEVACI 41000 € 45%2008 IRINO+CETUXI 60000 € 46%
Anno Schema Costo RR
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Aumento costo: 100 volte!...ma
Aumento risposte: 2.5
(dal 20% al 45%)
Aumento sopravvivenza: 2.5 volte (da 11 a 24 mesi)
COSTO-TRATTAMENTO CON COSTO-TRATTAMENTO CON FARMACI BIOLOGICI NEL CA FARMACI BIOLOGICI NEL CA COLORETTALE AVANZATOCOLORETTALE AVANZATO
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Ma che fine fanno le risposte?
Benoist S. et al.:Complete response of colorectal liver
metastases after chemotherapy: does it mean cure? JCO, 2006, 24 (24) 3939-45
Fiorentini G. et al.:Complete response of colorectal liver
metastases after intra-arterial chemotherapy.
Tumori, 2008, 94 (4): 489-92
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Complete Response after CHT: does it mean a real cure?
COMPLETE RESPONSE
BENOIST S. IV-FOLFOX
FIORENTINI G.IA-FUDR
N° PT treated 586 256
N° PT selected 38 46
Lesions with CR 66 106
Resected positive 20 (32%) 52 (49%)
Resected no evidence 15 (25%) 35 (29%)
Positive 12 (80%) 22 (34%)
Not visible relapsed 1 year
23/31 (60%) 33/106 (30%)
Not visible relapsed 2 years
ND 86 (81%)
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RATIONALE OF INTRA ARTERIAL HEPATIC
INFUSION-OCCLUSIONThe advantage of delivering chemotherapy by
hepatic arterial infusion is the administration of high-dose of the drug into the target
TACE is a combination of local drug infusion with selective embolization of the feeding arteries of the liver metastases. Normal liver parenchyma is fed by
a double vascularization (portal vein and hepatic artery)
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DRUG CONCENTRATION AND RETENTION REDISTRIBUTION OF BLOOD FLOW TO HYPOVASCULAR AREAS
INCREASED LIVER EXTRACTION
IMPROVED QUALITY OF LIFE
INCREASEDSURVIVAL
BETTER COMPLIANCEDUE TO LOWERSIDE EFFECTS
INCREASED THERAPEUTIC EFFICACY & REDUCED TOXICITY
TEMPORARYVASCULAR BLOCKING
REGIONALLY ADMINISTERED
CHEMOTHERAPY
Drug-Eluting Bead with Irinotecan (DEBIRI)
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In-Vitro Irinotecan loading of microsphere made from a compressible polyvinyl alcohol hydrogel
Images of 500-700 m microsphere before and after irinotecan loading.
No drug loading
1 hour of loading with 40 mg/mL of irinotecan.
Active uptake of drug into beads from irinotecan solution by ion-exchange mechanism
Loadings up to 50 mg/mL beads
Complete loading achieved within 60-120 min (bead size + drug loading dependent)
Drug loading accompanied by small decrease in average bead diameter
Slight change in colour from blue to turquoise
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AUTHORAUTHOR n° n° PtsPts TACETACE DRUGDRUG OCCLUSIVE OCCLUSIVE
AGENTAGENTRR RR %%
MEDIAN MEDIAN SURVIVAL SURVIVAL monthsmonths
Aliberti Aliberti 20062006 1010 22 IRIIRI DC BeadDC Bead 7070 --
Morise Morise 20062006 55 22 IRI, MMCIRI, MMC DSMDSM 8080 --
Muller Muller 20032003 6666 4.54.5 Melph, FU, Melph, FU,
GM - CSFGM - CSFLUF, LUF,
GelfoamGelfoam 7676 --
Popov Popov 20022002 1111 11 MMCMMC GelfoamGelfoam 5050 99
Voigt Voigt 20022002 1010 4.34.3 MMC, IFN, MMC, IFN,
OX, FUOX, FU DSMDSM 5050 --
You Y-T You Y-T 20062006 4040 11 FU, LVFU, LV LUFLUF 4848 1616
Fiorentini Fiorentini 20072007 2020 2.32.3 IRIIRI DC BeadDC Bead 8080 6.76.7
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THIRD LINE TREATMENT: COMPARING RESULTS
TACE SYSTEMICCHT
N° PATIENTS 1532(22 REPORTS)
2860(9 REPORTS)
RESPON. RATE 66% (40-82) 36% (18-48)
TIME TO PD 18 wks (2-60) 12 wks (2-42)
SURVIVAL 12.4 m. (5.5-26) 8.7 m. (4.5-21)
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Memorandum
• Fatto : ciò che è reale verificato
• Opinione : giudizio individuale, punto di vista soggettivo
• Evidenza : rilievo oggettivo che rende una cosa innegabile
Sabatini Coletti, Dizionario della lingua Italiana
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Level of evidence
Type of study Grade of recommendation
1 ++ High quality meta-analyses, systematic reviews of RCTs, RCTS with low risk of bias
A
1 + Well conducted meta-analyses, systematic reviews of RCTs, RCTS with low risk of bias
A or B
1 - Meta-analyses, systematic reviews of RCTs, RCTS with high risk of bias
B
2 ++ High quality syst. reviews of case-control/cohort studies. High quality case-control/cohort studies with very low risk of bias and high probability of causal relationship
B
2 + Well conducted case control/cohort studies with low risk of bias and moderate probability of causal relationship
C or D
2 - Case control/cohort studies with high risk of bias and significant risk of non-causal relationship
C or D
3 Non-analytic studies (case reports, case series) D
4 Expert Opinion D
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37
G. Fiorentini1, C. Aliberti 2, B. Corti3, M. Tilli2, A.Mambrini4,
G. Benea2
1 Oncology Unit, Department of Medicine, San Giuseppe General Hospital Empoli, University of Florence, Italy2 Interventional Radiology Unit, Department of Radiology, Delta Hospital, Ferrara, Italy 3 Department of Pathology, S. Orsola Hospital, University of Bologna, Italy 4 Department of Oncology, General Hospital, Carrara , Italy
DEBIRI RESULTS AND PATIENTS SELECTION IN DEBIRI RESULTS AND PATIENTS SELECTION IN METASTATIC DISEASE:EXPERIENCE OF ITALIAN METASTATIC DISEASE:EXPERIENCE OF ITALIAN
COOPERATIVE GROUP ANDCOOPERATIVE GROUP ANDTHE ONCOLOGIST PERSPECTIVETHE ONCOLOGIST PERSPECTIVE
ROMA 4°, March,2011ROMA 4°, March,2011
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Intra-arterial treatment of liver metastases with drug eluting beads: General Report (From March 2006 to July 2010)
•314 patients are treated •624 TACE•99% technical success
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Colorectal Cancer: 174
Uveal melanoma: 64
Cholangioca: 40
Pancreatic Cancer: 6
Breast Cancer: 14
Gastric Cancer: 6
Carcinoid: 8
Sarcoma: 6
Willms Cancer: 2
Irinotecan Doxorubicin
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LIVER METASTASES - COLORECTAL LIVER METASTASES - COLORECTAL CANCER CANCER
174 patients treated with DEBIRI
348 TACE348 TACE
99% technical success
72% evidence of clinical response
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•Diagnostic angiography (DSA) was performed •Under fluoroscopic guidance, a solution of DC beads loaded with Irinotecan and mixed with non-ionic c.m. was injected into the artery feeding the metastases.
Drug administrationDrug administration
Site of injection
Right hepatic artery
Left hepatic artery
Left and Right hepatic artery
138/348
(40%)
122/348
(35%)
87/348
(25%)
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LIVER METASTASES - OCULAR LIVER METASTASES - OCULAR MELANOMAMELANOMA
64 pretreated patients received DEBIRI
89 TACE89 TACE
100% technical success
90% evidence of response
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82 pretreated patients received DEBIRI
92 TACE92 TACE
100% technical success
60% evidence of response
LIVER METASTASES – MISCELLANEALIVER METASTASES – MISCELLANEA
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THE PYRAMID OF EVIDENCETHE PYRAMID OF EVIDENCE
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DEBIRI: STARTING POINT DEBIRI: STARTING POINT FOR THE ONCOLOGISTFOR THE ONCOLOGIST
CASE REPORTSRANDOMIZED STUDY
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FEMALE, 46 yrs, PARTIAL RESPONSE AFTER FEMALE, 46 yrs, PARTIAL RESPONSE AFTER FOLFOX + BEVAFOLFOX + BEVA
DEBIRI AS INTENT TO SURGERYDEBIRI AS INTENT TO SURGERY
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Obstruction of the celiac artery
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Retrograde canulation of the right hepatic artery
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perfusion limited to the right liver
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DEBIRIAFTERFOLFOX + BEVA
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RIGHT LIVER PERFUSED: 80% of NECROSIS
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LEFT LIVER NOT PERFUSED: 10% of NECROSIS
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1 month after TACE
6 months after TACE
FEMALE, 64YRS, REFUSED FEMALE, 64YRS, REFUSED SECOND TACE ON LEFT LIVERSECOND TACE ON LEFT LIVER
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TREATMENT CHOICES FOR PATIENTS WITH COLORECTAL LIVER METASTASES, BEARING IN MIND THE TYPE OF CHEMOTHERAPY
MAYBE THE SAME IN ALL THREE CLINICAL SITUATIONS.
Nordlinger B et al. Ann Oncol 2009
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Advanced colorectal cancer
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0 6 12 18 24
Median overall survival (months)
BSC ~ 4–6 months
16–18 monthsFU + IRI or OXA
20 monthsFU + IRI + OXA
9 months5-FU
11-12 monthsFU+LV or CI FU
12-13 monthsBolus/CI FU
90’s
2000’s
2004-2005CT+biological
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Prospective studies on non-resectable liver metastases
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RegimenRegimen NN RRRR ResectionResection AuthorAuthor
IFL 264 31% 1% GoldbergGoldberg
FOLFOX 267 45% 4%
IROX 265 35% 4%
AIO 216 34% 1% KöhneKöhne
AIO+IRI 214 64% 3%
FOLFIRI 109 56% 9% TournigandTournigand**
FOLFOX 111 54% 22%
FOLFIRI 178 34% 5.1% ColucciColucci
FOLFOX 182 36% 4.4%
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• STEATOSIS
5-FU
• STEATO-HEPATITIS
Irinotecan
• SINUSOIDAL OBSTRUCTION
Oxaliplatin
CHEMOTHERAPY INDUCED LIVER DAMAGE
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PAM-IRI (DEBIRI-D) VS FOLFIRI (CT) PAM-IRI (DEBIRI-D) VS FOLFIRI (CT) WHY A RANDOMIZED STUDY?WHY A RANDOMIZED STUDY?
LM from CRC occur in 50% of patients and we need new possibilities of cure.
5-year survival after resection is 25-35%, but recurrence is common.
For unresectable LM the survival is 5% at 5 years.
Palliative chemotherapy is the main stay of treatment.
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PAM-IRI (DEBIRI-D) VS FOLFIRI (CT) PAM-IRI (DEBIRI-D) VS FOLFIRI (CT) WHY A RANDOMIZED STUDY?WHY A RANDOMIZED STUDY?
Chemotoxicity is common and median survival is about 18 months, although this had a slightly increase adding monoclonal antibodies and angio-inhibitors (22 months).
Ablative or trans-arterial techniques allow localised, minimally invasive therapy without systemic toxicity or morbidity.
Catheter-delivered arterial treatments include TACE with PAM are effective in phase II studies.
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PAM-IRI (D) is a combination of local drug infusion with selective embolization of the LM feeding arteries.
feasible and safe (ASCO-GI 2007, abs # 356; IN VIVO 2007, 21, 6; ASCO-GI 2008 abs # 480).
The study was designed to show an increase of 40% of median overall survival (MS, primary endpoint) at 2 years follow-up (HR= 0.72 by Kaplan Meier method).
Response rate, Progression Free Survival and Quality of Life (Edmonton Symptom Score) were secondary endpoints. We report an analysis at 30 months median follow-up.
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PAM-IRI (DEBIRI-D) VS FOLFIRI (CT) PAM-IRI (DEBIRI-D) VS FOLFIRI (CT) WHY A RANDOMIZED STUDY?WHY A RANDOMIZED STUDY?
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POLYVINIL-ALCOHOL MICROSPHERES POLYVINIL-ALCOHOL MICROSPHERES (PAM) AND IRINOTECAN: BASIC DATA(PAM) AND IRINOTECAN: BASIC DATA
PAM were prepared loading irinotecan 50 MG /mL. Irinotecan loading happened by an ion-exchange mechanism with sulfonate binding sites in the PAM.
This did not influence the ability to be suspended in contrast agent or delivered through a catheter.
Taylor RR et al (Eur J Pharm Sci. 2007 Jan;30(1):7-14.) observed that following porcine hepatic artery infusion of PAM-IRI, maximum plasma levels were 75% lower for irinotecan compared to intra-arterial bolus administration
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RANDOM74 pts
DEBIRI 2 treatments
36 pts
FOLFIRI8
administrations38pts
RANDOMIZED STUDY:RANDOMIZED STUDY:PAM-IRI (DEBIRI-D) VS FOLFIRI PAM-IRI (DEBIRI-D) VS FOLFIRI
(CT)(CT)
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Patients and MethodsPatients and Methods
From December 2006 to December 2008, 74 pts (M/F=49/25; median age 64) were randomized.
36 to D (PAM loaded with 200 mgr IRI) once a month for 2 times and 38 pts to FOLFIRI (IRI 180mg/m² on Day 1 with LV 100 mg/m² as 2-hour infusion, followed by FU 400 mg/m² bolus and FU 600mg/m² as 22-hour infusion on Days 1 and 2 every 2 weeks for 8 times (4 months of treatment).
Ondansetron 8 mg and Dexamethasone 12 mg were provided to CT Arm.
Intravenous hydration, morphine, anti-emetic and antibiotic prophylaxis were provided to D patients to reduce post embolization effects.
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DEBIRI FOLFIRI
NUMBER OF PATIENTS
36 38
2/3 lines CT 23/13 24/14
25%-50% liver
involvement
26/10 26/12
K-RAS WT/M 22/14 26/12
PATIENTS CHARACTERISTICSPATIENTS CHARACTERISTICS
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PAM-IRI (D): Supportive therapyPAM-IRI (D): Supportive therapy(Fiorentini G. et al: (Fiorentini G. et al: Hepatogastroenterology 2008;
55(88):2077-82)
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Intra-venous hydration Intra-venous hydration started day -1 and started day -1 and continued on day 0, +1, +2continued on day 0, +1, +2
2000ml bag/24h infusion(1000ml of saline solution, 1000ml of glucose 5%) with the addition of Ranitidine 900mg
Intra-venous hydration Intra-venous hydration started day -1 and started day -1 and continued on day 0, +1, +2continued on day 0, +1, +2
2000ml bag/24h infusion(1000ml of saline solution, 1000ml of glucose 5%) with the addition of Ranitidine 900mg
Prophylactic treatment Prophylactic treatment against infectionagainst infection
Cefazolin 2000mg iv at 08.00 am and at 08.00 pm day 0,+1,+2
The supportive treatment goes on if required on day+3, +4, +5
Prophylactic treatment Prophylactic treatment against infectionagainst infection
Cefazolin 2000mg iv at 08.00 am and at 08.00 pm day 0,+1,+2
The supportive treatment goes on if required on day+3, +4, +5
Prophylactic treatment Prophylactic treatment against painagainst pain
Morphine 10mg, 1 vial i.v, 30 minutes before PAM-IRI and 1 at +6 hoursIntra-arterial Lidocaine 5ml just before PAM-IRI
Prophylactic treatment Prophylactic treatment against painagainst pain
Morphine 10mg, 1 vial i.v, 30 minutes before PAM-IRI and 1 at +6 hoursIntra-arterial Lidocaine 5ml just before PAM-IRI
Prophylactic treatment Prophylactic treatment against nauseaagainst nausea Tropisetron 5mg, 1 vial i.v. before and 1 at +6 hours, Prednisone 25mg orally (or Desamethasone 8 mgr iv) at 08.00 am and at 08.00 pm day 0,+1,+2,+3,+4,+5
Prophylactic treatment Prophylactic treatment against nauseaagainst nausea Tropisetron 5mg, 1 vial i.v. before and 1 at +6 hours, Prednisone 25mg orally (or Desamethasone 8 mgr iv) at 08.00 am and at 08.00 pm day 0,+1,+2,+3,+4,+5
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PAM-IRI (DEBIRI-D) PAM-IRI (DEBIRI-D) AdministrationAdministration
Diagnostic angiography (DSA) was performed. Under fluoroscopic guidance, a solution of 4 ml of PAM loaded with IRI 200mg and mixed with non-ionic contrast medium was injected into the artery feeding the metastases.
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Complete loading achieved within 2 hours (PAM size is drug loading dependent)
Slight change in colour from blue to turquoise
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No drug loaded loaded with IRI
PAM-IRI (DEBIRI-D) PreparationPAM-IRI (DEBIRI-D) Preparation
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ResultsResults4 out of 38 FOLFIRI patients were not evaluable (2 declined and 2 refused). 1 out 36 DEBIRI patient had early disease progression.34 and 35 patients were evaluated respectively for this interim report at a median follow-up of 30 months. 72 cycles of DEBIRI with a relative dose intensity of 99% and 292 FOLFIRI cycles with a relative dose intensity of 90% were administered. Median overall survival results are adjusting for one interim analysis. 67
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OBSERVED TOXICITY (G2-G3)OBSERVED TOXICITY (G2-G3)
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TOXICITYTOXICITY DEBIRI (D)DEBIRI (D) FOLFIRI (CT)FOLFIRI (CT)
PAIN (G2) 30% 0%
VOMITING (G2) 25% 25%
DIARRHOEA 2% 35%
ASTHENIA 20% 50%
LEUCOPENIA 5% 35%
ANEMIA 5% 35%
FEVER (G3) 15% 3%
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APPEARANCE OF TOXICITY IN APPEARANCE OF TOXICITY IN PAM – IRI (DEBIRI-D) ARMPAM – IRI (DEBIRI-D) ARM
0
5
10
15
20
25
30
35
40
0
1 ho
ur
6 ho
urs
12 hou
rs
18 hou
rs
1 da
y
2 da
y
1 wee
k
2 wee
k
Pro
cedure
s
Pain Vomiting Fever Asthenia
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RESULTS RESULTS ( median follow up 30 months range 18-36)( median follow up 30 months range 18-36)
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ARMSARMSOverall Overall Surviv.Surviv.
(%)(%)
ResponseResponse
PFSPFSmonthsmonths
AcuteAcuteToxicityToxicity(G2-G3)(G2-G3)
LateLatetoxicitytoxicity(G2)(G2)
EdmontonEdmontonScoreScore
improvementimprovement(Δ from (Δ from baseline)baseline)
CostsCosts(Euros)(Euros)
DD(n=34) (n=34)
3868%
6.470% 20% 60%
6,450Each
Pt.( x 2 D)
CTCT(n=35)(n=35)
1518%
3.225% 80% 22%
10,250Each Pt
( x 8 CT)
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SURVIVAL EVALUATED AT 24 SURVIVAL EVALUATED AT 24 MONTHSMONTHS
SU
RV
IVA
L %
TIME (days)
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PAM-IRI Case 1PAM-IRI Case 1Partial remission lasting 190 days Partial remission lasting 190 days
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PAM-IRI Case 2PAM-IRI Case 2Partial remission lasting 150 daysPartial remission lasting 150 days
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CASE 3: PARTIAL REMISSION LASTING 240 DAYSCASE 3: PARTIAL REMISSION LASTING 240 DAYS
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ConclusionsConclusions We observed that D increased the 24 months OS difference
of 22% compared to CT. D improved responses, PFS, performance status and reduced
costs compared to CT. D reported higher immediate toxicity, mainly fever, abdominal
pain, nausea and vomiting, than CT. Intravenously hydration, morphine and antibiotics are necessary to control these symptoms. Late toxicity, mainly leukopenia, anemia, diarrhoea, asthenia and alopecia were more common in CT.
We conclude that D reaches the goal to increase 2-Y MS compared to CT.
Our study is the first one in Literature which reports a clear survival benefit of PAM-IRI (D) over Systemic Chemotherapy (CT).
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LESSONS LEARNED: THE LESSONS LEARNED: THE ONCOLOGIST PERSPECTIVEONCOLOGIST PERSPECTIVE
High response rate, prolonged survival,costs reduction in pretreated colon
cancer patientsActivity in K Ras WT/M
Probably the best treatment in ocular melanoma patients
Effective palliation in preminent liver metastases from other tumours
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THE PYRAMID OF EVIDENCETHE PYRAMID OF EVIDENCE
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WE ARE WE ARE HERE!!HERE!!
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SurgeonRadiologist
Oncologist Nurse
Histopathologist
THE MULTIDISCIPLINARY TEAM