Μάριος Μπακογεώργος Παθολόγος-Ογκολόγος Ογκολογική Κλινική 251 ΓΝΑ Αθήνα 28/2/2015 Μεταστατικός Καρκίνος Ουροδόχου Κύστης

Ε π ιδημιολογία Stage at diagnosis %5yr survival In situ – Τa T1-T4 N0 M Regional LNs732.9 Distant Metastasis (M1)45.5 Unknown stage348.8

Ιστολογικοί τύ π οι TCC ~ 90% Squamous Ca ~ 8% Adenocarcinomas Sarcomas Lymphomas 2% SCC Carcinoid tumors

Sites of metastasis Lymph Nodes 69% Bones 47% Lungs 37% Liver 26% Peritoneum 16% CNS Skin Shinagare et al. AJR 2011

Stage IV Bladder Cancer Resectable (potentially) multimodality treatment (Cystectomy and/or XRT following systemic CMT) Unresectable chemotherapy Median Survival: 14 months

Prognostic factors in 1st line 203 pts Urothelial cancer Stage IV MVAC

Active CMT agents ΦάρμακαΑντικειμενικές ανταποκρίσεις Cisplatin35% Vinblastine18% Doxorubicin5% Methotrexate26% Gemcitabine28% Paclitaxel42% Docetaxel31%

Ξεκινώντας με Cisplatin…

Combination Regimens CMV CISCA MVAC

246 ασθενείς 120 Cisplati n 126 MVAC CisplatinMVAC ORR12% (CR: 12%) 39% * (CR: 12%) PFS 4.3 m 10.0 m * OS 8.2 m 12.5 m * Cisplatin (q4w) 70 mg/m2 (d1) MVAC (q4w) Methotrexate 30 mg/m2 (d1,15,22) Vinblastine 3 mg/m2 (d2,15,22) Adriamycin 30 mg/m2 (d2) Cisplatin 70 mg/m2 (d2) MVAC: more toxicity {febrile neutropenia, mucositis, alopecia, nausea/vomiting}

MVAC vs CDDP Loehrer et al. JCO 1992 PFS OS

CDDP/GMB vs MVAC 405 ασθενείς 203 GC202 MVAC

CDDP/GMB vs MVAC PFS

CDDP/GMB vs MVAC OS

CDDP/GMB vs MVAC

CDDP/GMB vs MVAC: long term Follow up 5-year PFS: 10% vs 11% 5-year OS: 13% vs 15% Von der Maase et al. JCO 2005

High Dose Intensity vs Classic MVAC 263 ασθενείς 134 HD- MVAC 129 MVAC HD-MVAC (q2w) (+G-CSF) Methotrexate 30 mg/m2 (d1) Vinblastine 3 mg/m2 (d1) Adriamycin 30 mg/m2 (d1) Cisplatin 70 mg/m2 (d1) MVAC (q4w) Methotrexate 30 mg/m2 (d1,15,22) Vinblastine 3 mg/m2 (d2,15,22) Adriamycin 30 mg/m2 (d1) Cisplatin 70 mg/m2 (d1) Sternberg et al. JCO 2001

High Dose Intensity vs Classic MVAC Sternberg et al. JCO 2001, EJC 2006 HD-MVACMVAC ORR62% * (CR: 21%) 50% (CR: 9%) PFS9.5 m*8.1 m OS15.1 m14.9 m HD-MVAC: N/V, thrombocytopenia (1 toxic death) MVAC: Febrile neutropenia, Mucositis (1 toxic death)

High Dose Intensity vs Classic MVAC Sternberg et al. EJC year PFS: 16.5% vs 8.0%5-year OS: 21.8% vs 13.5%

DD-GCDD-MVAC RR65% (CR: 10%) 60% (CR: 11%) PFS7.8 m8.5 m OS18.0 m19.0 m MVAC: Febrile neutropenia Treatment discontinuation

1st line CMT: Υ π άρχει ρόλος για τις ταξάνες;

220 ασθενείς 111 DC109 MVAC DCMVAC ORR37% (CR: 13%) 54% * (CR: 23%) TTP6.1 m9.4 m* OS9.3 m14.2 m* Bamias et al. JCO 2004

85 ασθενείς 41 PC44 MVAC PCMVAC ORR28% (CR: 3%) 36% (CR: 13%) PFS5.2 m8.7 m* OS13.8 m15.4 m Dreicer et al. Cancer 2006

1st line CMT: Υ π άρχει ρόλος για π ροσθήκη 3 ου φαρμάκου ;

Bellmunt et al. JCO 2006 OS: όφελος σε ε π ιλεγμένους ασθενείς 626 ασθενείς 312 PGC314 GC PGCGC RR55% (CR: 12%) 44% (CR: 12%) PFS8.3 m7.6 m OS15.8 m12.7 m

Carboplatin instead of Cisplatin? 50%: unfit for Cisplatin PS ≥ 2 Cl Cr < 60 ml/min Sensory Neuropathy ≥ grade II Hearing impaired ≥ grade II CHF ≥ NYHA class III MCaVi Similar Efficacy, Carbo/GMB: less toxic Carboplatin/Gemcitabine Taxanes Gemcitabine

Prognostic factors in 2nd line

370 ασθενείς 253 Vinflunine 117 BSC VinflunineBSC ORR9% (CR: 0%) 0% * (CR: 0%) PFS3.0 m 1.5 m * OS6.9 m4.6 m Bellmunt et al. JCO 2009 Clinical Benefit Survival benefit in fit pts

Yafi et al. Current Oncology 2011

ευχαριστώ πολύ…