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

2. 25 percent of patients will have muscle-invasive disease and either present with or later develop metastases The prognosis for patients with metastatic disease is poor Systemic chemotherapy is the standard approach for patients with inoperable locally advanced or metastatic disease Although response rates are high compared to many other advanced solid malignancies, the median survival with aggressive chemotherapy treatment is only about 14 months While this is superior to the estimated six-month survival with metastatic disease prior to modern chemotherapy regimens the five-year survival rate is approximately 15 percent with current combination regimens

3. PROGNOSTIC FACTORS A poor performance status the presence of visceral (ie, pulmonary, liver, bone) metastases correlate with shortened survival in clinical trials elevated alkaline phosphatase mutations in the p53 gene The excision repair cross complementing 1 (ERCC1) gene levels

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

5. COMBINATION CHEMOTHERAPY cisplatin regimens methotrexate, vinblastine, doxorubicin, and cisplatin (MVAC) Toxicity is a serious consideration with MVAC, particularly since many patients with bladder cancer are elderly or have multiple comorbidities 54 percent of patients in one series were hospitalized due to toxicity gemcitabine plus cisplatin Paclitaxel, cisplatin, gemcitabine docetaxel plus cisplatin

6. Carboplatin regimens substantial activity for these combinations particularly for elderly patients and those with renal impairment gemcitabine carboplatin carboplatin and paclitaxel

7. Nonplatinum regimens paclitaxel plus gemcitabine docetaxel plus gemcitabine

8. UNFIT PATIENTS carboplatin-based combinations and non- platinum regimens may offer significant benefit in carefully selected patients. single 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 gemcitabine plus carboplatin methotrexate, carboplatin, plus vinblastine (M-CAVI)

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

10. SECOND-LINE CHEMOTHERAPY Pemetrexed, a multitargeted antifolate Ixabepilone, an epothilone B analog, targets the microtubules Vinflunine, a novel vinca alkaloid, Eribulin (E7389) is a synthetic macrocyclic ketone analogue Taxanes

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

12. radiotherapy