Treatment for metastatic bladdercancer chemotherapyradiotherapy Dr Mina Tajvidi

Treatment for metastatic bladdercancer (chemotherapy&radiotherapy) Dr. Mina Tajvidi oncologist

25 percent of patients will have muscle-invasive disease and either present with or later develop metastases üThe prognosis for patients with metastatic disease is poor üSystemic chemotherapy is the standard approach for patients with inoperable locally advanced or metastatic disease ü Although response rates are high compared to many other advanced solid malignancies, the median survival with aggressive chemotherapy treatment is only about 14 months üWhile this is superior to the estimated sixmonth survival with metastatic disease prior to modern chemotherapy regimens ü the five-year survival rate is approximately 15 percent with current combination regimens ü

PROGNOSTIC FACTORS üA poor performance status ü the presence of visceral (ie, pulmonary, liver, bone) metastases correlate with shortened survival in clinical trials ü elevated alkaline phosphatase ümutations in the p 53 gene üThe excision repair cross complementing 1 (ERCC 1) gene levels

SINGLE AGENT CHEMOTHERAPY cisplatin, carboplatin, doxorubicin, methotrexate, and vinblastine Newer agents with significant clinical activity include ifosfamide , paclitaxel , docetaxel, and gemcitabine üResponses to single agent chemotherapy are generally of short duration, and no consistent improvement in survival has been demonstrated.

COMBINATION CHEMOTHERAPY cisplatin regimens ümethotrexate, vinblastine, doxorubicin, and cisplatin (MVAC) üToxicity is a serious consideration with MVAC, particularly since many patients with bladder cancer are elderly or have multiple comorbidities ü 54 percent of patients in one series were hospitalized due to toxicity ü gemcitabine plus cisplatin üPaclitaxel, cisplatin, gemcitabine üdocetaxel plus cisplatin

Carboplatin regimens üsubstantial activity for these combinations üparticularly for elderly patients and those with renal impairment ügemcitabine carboplatin ücarboplatin and paclitaxel

Nonplatinum regimens üpaclitaxel plus gemcitabine üdocetaxel plus gemcitabine

UNFIT PATIENTS carboplatin-based combinations and nonplatinum regimens may offer significant benefit in carefully selected patients. üsingle agent therapy with gemcitabine or paclitaxel and various two-drug combinations in which carboplatin is substituted for cisplatin are feasible and have activity in these populations ügemcitabine plus carboplatin ümethotrexate, carboplatin, plus vinblastine (M-CAVI) ü

SECOND-LINE CHEMOTHERAPY üpatients have failed on MVAC or GC üPaclitaxel , docetaxel [28], gemcitabine , ifosfamide , and oxaliplatin üReported response rates with single agents in the larger series have generally been 20 percent or less. üAlthough these drugs have also been combined with either each other or with other agents none are considered to be standard second-line therapy. üPatients with advanced bladder cancer should be encouraged to participate in clinical trials whenever possible.

SECOND-LINE CHEMOTHERAPY üPemetrexed, a multitargeted antifolate Ixabepilone, an epothilone B analog, targets the microtubules Vinflunine, a novel vinca alkaloid, Eribulin (E 7389) is a synthetic macrocyclic ketone analogue Taxanes

TARGETED THERAPY üVEGF pathway - Bevacizumab - Aflibercept – Sunitinib ü EGFR pathway - Gefitinib - Cetuximab - Trastuzumab - Erlotinib – Lapatinib ü Multitargeted TK inhibitors - Sorafenib - Pazopanib - Vandetanib

radiotherapy