Transcript Diapositiva 1

L’impiego di nab-paclitaxel nel
trattamento terapeutico del
carcinoma mammario metastatico
(in prima/seconda linea)
Dr. Salvatore Bonura
ASS 5 Bassa Friulana
Ospedali di Latisana e Palmanova
(UD)
Sesso F
Età
43 anni
Premenopausa
2005 Mastectomia sinistra + protesi
K duttale inf. G2 pT2 N+ (1/16 N ) ER 90% PgR 70% HER 2 neg
FEC x 6 adiuvante > Analogo LH/RH + TAM
2009 rec sottocutanea sin (QQII diam. 1,5 cm) 
Asportazione
K duttale inf. G3 ER 95% PgR 5% Mib 1 30% HER 2 neg
LETROZOLO
FEBBRAIO 2012 recidiva periprotesica
(sottocutaneo) sin ( 0,5 cm)
Ca duttale infiltrante scarsamente differenziato ER > 95% PgR neg
Mib1 40% HER 2 neg
Citologia + su LNF iuxtaclaveare
PET/TC (marzo) linfoadenopatie in sede mediastinica-claveare sx
compatibili con localizzazioni secondarie di malattia
Intervento
• APRILE 2012 inizia CHT
Nab Paclitaxel 260 mg / mq /Q3W (1 ciclo)
Nab Paclitaxel 125 mg / mq / settimana
(Schedula 3 w on/ 1 w off) (2 cicli: 6 sedute)
Dopo 3 cicli: Buona RP
Eventi avversi
Tossicità ( Q3W ): nausea G2, stomatite G2,
artralgie-mialgie G3 (7-10 giorni)
Tossicità ( QW ): nausea G1
“Terapia impegnativa per la frequenza (impegno mentale)”
“ L’effetto peggiore è stato l’alopecia”
Ha ripreso il trattamento QW x 2 cicli
(Paziente estremamente motivata)
Nausea-stomatite G1 - Artralgie scapolo-omerali G1
In attesa di rivalutazione
Riepilogo caso clinico - Fasi del
trattamento ed evoluzione clinica
corrispondente
Periodo
Trattamento
2005
Mastectomia
(protesi)+LAD sx
Evoluzione clinica
PT2 N+ (1/16) G2 RO++
HER 2 neg
FEC x 6 adiuvante
Tamoxifene + LH-RH
ASSENZA DI MALATTIA
Tamoxifene
Recidiva sottocutanea sx (diam. 1,5 cm)
K G3 RO+- Mib1 30% HER2 neg
2009 > 2012
(ASPORTAZIONE
LETROZOLO)
Assenza di malattia
Febbraio-Marzo
2012
Letrozolo
Aprile-Maggio-Giugno
2012
NAB-P x 3 cicli (1° > Q3W
2°-3° > QW )
Recidiva sottocutanea sx (diam. 0,5 cm)
K G3 RO+- Mib1 40% HER2 - PET/TC: LNFpat mediast-clav
sin
Agosto-Settem. 2012
NAB-P x 2 cicli - QW
2006
2009
Remissione parziale di malattia
In rivalutazione
Spunti di discussione:
Scelta del trattamento
Scelta della schedula
Come proseguire
5-Year Survival Rates by Stage
Stage 0 (95%)
Stage I (88%)
Stage II (66%)
Stage III (36%)
Stage IV (7%)
http://www.nlm.nih.gov/medlineplus/ency/article/000913.htm
Advances in Treatment
1980
1985
1990
1995
2000
2005
Tamoxifen
CMF
Doxorubicin
Mitoxantrone
Epirubicin
Paclitaxel
Vinorelbine
Aromatase Inhibitors
ER+ or PR+
HER2+
Docetaxel
Gemcitabine
Capecitabine
Fulvestrant
Trastuzumab
Albumin-Bound Paclitaxel
Bevacizumab
Lapatinib
Ixabepilone
Need for Better Therapies and Patient
Selection to Improve Survival
Drug resistance is associated with >90% treatment
failures in patients with metastatic cancer1
5-year survival of patients diagnosed with MBC is
approximately 26%,2 despite considerable
therapeutic advances over the past 20 years3
Improved selection of patients for response to
available therapies will result from genomic and
proteomic analyses3
1. Longley and Johnson. J Pathol. 2005;205:275.
2. American Cancer Society. Cancer Facts & Figures 2007. Atlanta: American Cancer Society; 2007.
3. Seidman. Oncology (Williston Park). 2006;30:983.
First-Line MBC
Single-Agent Response Rates
Treatment
Docetaxel1 (75-100 mg/m2)
Paclitaxel1 (175-250 mg/m2 3-24 h)
Doxorubicin4
Capecitabine3
Vinorelbine2
Gemcitabine2
Cyclophosphamide4
Fluorouracil4
Methotrexate4
Mitoxantrone4
ORR (%)
40-68
32-62
43
30
35-53
18-37
36
28
26
27
1. Seidman AD, Clin Cancer Res 2.Vogel and Nabholtz. The Oncologist. 1999;4:17.
3. O’Shaughnessy et al. Ann Oncol. 2001;12:1247.4. Sledge. Cancer Control. 1999;6:17.
Taxanes as Adjuvant Therapy in
Taxanes used in stage I-III BC significantly improves DFS
Recurrence is still a substantial problem
Emergence of molecular resistance to taxanes:
Increases population requiring alternate therapy
Decreases efficacy to other chemotherapies
by cross-resistance
BC
Clinical Challenges
in the Management of MBC
Individualizing treatment to specific cancer biology
Reducing and managing toxicity of chemotherapies
Understanding and then overcoming resistance to
chemotherapy and hormone therapy
Impact in metastatic and adjuvant settings
Increasing disease control and survival
Rationale for New Agents
MBC remains an important medical problem
Anthracyclines and taxanes are the standard of care
Increasing use in the adjuvant setting
Drug resistance
Need for new agents
Capecitabine approved for use after failure of anthracyclines
and/or taxanes
ORRs 9% to 14% in phase III studies1,2
Limited efficacy of other agents used in MBC
1. Miller et al. J Clin Oncol. 2005;23:792.
2. Geyer et al. N Engl J Med. 2006;355:2733.
Le Linee-Guida:
NAB-paclitaxel e altri taxani
• Paclitaxel viene raccomandato in prima linea in monoterapia o in
associazione a bevacizumab
• Raccomandato anche l’utilizzo di NAB-paclitaxel alla posologia
di 100-150 mg/m2 ev ai giorni 1, 8 e 15 ogni 28 giorni, o alla
posologia di 260 mg/m2 ev ogni 21 giorni
• Terapia di prima linea con paclitaxel settimale in
monoterapia, paclitaxel associato ad antraciclina
(doxorubicina, epirubicina), a gemcitabina,
vinorelbina o carboplatino.
• Le Linee-guida ESMO suggeriscono anche
l’impiego del nuovo farmaco NAB-paclitaxel
Nell’aggiornamento 2010 delle linee guida AIOM NAB-paclitaxel è
stato inserito tra i farmaci molto attivi in monoterapia; si sottolinea
infatti che NAB-paclitaxel ha dimostrato di migliorare
significativamente la percentuale di risposte obiettive, TTP e OS nelle
donne con carcinoma mammario metastatico rispetto a paclitaxel
convenzionale disciolto in solvente
NCCN: Linee-guida MBC
No compelling evidence that combination regimens are superior to
sequential agents
HER2 -
HER2 +
16 preferred single agents/combinations
listed with no sequencing guidance
Anthracyclines
Taxanes
Doxorubicin
Paclitaxel
Pegylated
Liposomal
Doxorubicin
Albumin-bound
Paclitaxel
Epirubicin
Docetaxel
Antimetabolites
Capecitabine
Gemcitabine
Relatively clearer guidance for
HER2+ patients
First Line
(Trastuzumab
Naïve)
Trastuzumab +
Paclitaxel +/Carboplatin
Trastuzumab +
Docetaxel
Combo/Other
Vinorelbine
AC
DC
FAC/CAF
AT
GP
FEC
CMF
Other
Bevacizumab
Trastuzumab
Exposed
Capecitabine +
lapatinib
Trastuzumab +
Capecitabine
Trastuzumab +
lapatinib
Trastuzumab +
Vinorelbine
Trastuzumab +
Capecitabine
Trastuzumab +
HER2recommended
therapy
Chemotherapy Regimens for MBC
2007 NCCN Recommendations
Representative Single Agents
Doxorubicin
Combination Regimens
CAF/FAC (cyclophosphamide/doxorubicin/
fluorouracil)
Epirubicin
FEC (fluorouracil/epirubicin/cyclophosphamide)
Pegylated liposomal doxorubicin
AC (doxorubicin/cyclophosphamide)
Paclitaxel
EC (epirubicin/cyclophosphamide)
Docetaxel
Capecitabine
AT (doxorubicin/docetaxel;
doxorubicin/paclitaxel)
Vinorelbine
CMF (cyclophosphamide/methotrexate/fluorouracil)
Gemcitabine
Docetaxel/capecitabine
Albumin-bound paclitaxel
GT (gemcitabine/paclitaxel)
F = fluorouracil; A = doxorubicin; C = cyclophosphamide; E = epirubicin; T = paclitaxel; M = methotrexate.
National Comprehensive Cancer Network. Breast Cancer. Clinical Practice Guidelines in Oncology – v.2.2007.
NCCN: NAB-paclitaxel tra le
monochemioterapie raccomandate
in prima linea
Taxanes
Sequential
preferred