L’impiego di nab-paclitaxel nel trattamento terapeutico del carcinoma mammario metastatico (in...
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L’impiego di nab-paclitaxel nel trattamento terapeutico del carcinoma mammario metastatico (in prima/seconda linea) Dr. Salvatore Bonura ASS 5 Bassa Friulana
Limpiego 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)
Slide 2
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 Sesso F Et 43 anni Premenopausa
Slide 3
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
Slide 4
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
Ha ripreso il trattamento QW x 2 cicli (Paziente estremamente
motivata ) Nausea-stomatite G1 - Artralgie scapolo-omerali G1 In
attesa di rivalutazione
Slide 7
Riepilogo caso clinico - Fasi del trattamento ed evoluzione
clinica corrispondente PeriodoTrattamentoEvoluzione clinica 2005
Mastectomia (protesi)+LAD sx PT2 N+ (1/16) G2 RO++ HER 2 neg FEC x
6 adiuvante 2006 Tamoxifene + LH-RH ASSENZA DI MALATTIA 2009
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 Recidiva sottocutanea sx
(diam. 0,5 cm) K G3 RO+- Mib1 40% HER2 - PET/TC: LNFpat
mediast-clav sin Aprile-Maggio-Giugno 2012 NAB-P x 3 cicli (1 >
Q3W 2-3 > QW ) Remissione parziale di malattia Agosto-Settem.
2012 NAB-P x 2 cicli - QW In rivalutazione
Slide 8
Spunti di discussione: Scelta del trattamento Scelta della
schedula Come proseguire
Slide 9
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
Need for Better Therapies and Patient Selection to Improve
Survival Drug resistance is associated with >90% treatment
failures in patients with metastatic cancer 1 5-year survival of
patients diagnosed with MBC is approximately 26%, 2 despite
considerable therapeutic advances over the past 20 years 3 Improved
selection of patients for response to available therapies will
result from genomic and proteomic analyses 3 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.
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First-Line MBC Single-Agent Response Rates TreatmentORR (%)
Docetaxel 1 (75-100 mg/m 2 )40-68 Paclitaxel 1 (175-250 mg/m 2 3-24
h)32-62 Doxorubicin 4 43 Capecitabine 3 3030 Vinorelbine 2 35-53
Gemcitabine 2 18-37 Cyclophosphamide 4 36 Fluorouracil 4 28
Methotrexate 4 26 Mitoxantrone 4 27 1.Seidman AD, Clin Cancer Res
2.Vogel and Nabholtz. The Oncologist. 1999;4:17. 3.OShaughnessy et
al. Ann Oncol. 2001;12:1247.4.Sledge. Cancer Control.
1999;6:17.
Slide 13
Taxanes as Adjuvant Therapy in BC 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
Slide 14
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
Slide 15
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 studies
1,2 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.
Slide 16
Le Linee-Guida: NAB-paclitaxel e altri taxani Paclitaxel viene
raccomandato in prima linea in monoterapia o in associazione a
bevacizumab Raccomandato anche lutilizzo di NAB-paclitaxel alla
posologia di 100-150 mg/m 2 ev ai giorni 1, 8 e 15 ogni 28 giorni,
o alla posologia di 260 mg/m 2 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
limpiego del nuovo farmaco NAB-paclitaxel Nellaggiornamento 2010
delle linee guida AIOM NAB-paclitaxel 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
Slide 17
NCCN: Linee-guida MBC Trastuzumab Exposed Anthracyclines
Doxorubicin Pegylated Liposomal Doxorubicin Epirubicin Taxanes
Paclitaxel Albumin-bound Paclitaxel Docetaxel Anti- metabolites
Gemcitabine Capecitabine Combo/Other Vinorelbine FAC/CAF FEC AC AT
CMF DC GP Other First Line (Trastuzumab Nave) Trastuzumab +
Paclitaxel +/- Carboplatin Trastuzumab + Docetaxel Trastuzumab +
Vinorelbine Trastuzumab + Capecitabine Capecitabine + lapatinib
Trastuzumab + Capecitabine Trastuzumab + lapatinib Trastuzumab +
HER2- recommended therapy HER2 + HER2 - Relatively clearer guidance
for HER2+ patients 16 preferred single agents/combinations listed
with no sequencing guidance Bevacizumab No compelling evidence that
combination regimens are superior to sequential agents
Slide 18
Representative Single Agents Chemotherapy Regimens for MBC 2007
NCCN Recommendations Doxorubicin Epirubicin Pegylated liposomal
doxorubicin Paclitaxel Docetaxel Capecitabine Vinorelbine
Gemcitabine Albumin-bound paclitaxel CAF/FAC
(cyclophosphamide/doxorubicin/ fluorouracil) FEC
(fluorouracil/epirubicin/cyclophosphamide) AC
(doxorubicin/cyclophosphamide) EC (epirubicin/cyclophosphamide) AT
(doxorubicin/docetaxel; doxorubicin/paclitaxel) CMF
(cyclophosphamide/methotrexate/fluorouracil) Docetaxel/capecitabine
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. Combination Regimens
Slide 19
Slide 20
NCCN: NAB-paclitaxel tra le monochemioterapie raccomandate in
prima linea