Gemcitabine Hydrochloride and Eribulin Mesylate in Treating Patients With Bladder Cancer That is Advanced or Cannot Be Removed by Surgery

Patients must have locally advanced or metastatic predominantly urothelial carcinoma of the bladder, ureter, or urethra that is not amenable to curative surgical treatment

Patients must have histologically confirmed predominantly urothelial carcinoma of the bladder, ureter, or urethra

Patients must have measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) criteria, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded for non-nodal lesions and short axis for nodal lesions) as \>= 20 mm with conventional techniques or as \>= 10 mm with spiral computed tomography (CT) scan, magnetic resonance imaging (MRI), or calipers by clinical exam

Patients must be ineligible for treatment with cisplatin, based on one of:

* Calculated creatinine clearance (CrCl) \>= 30 and \< 60 mL/min (Cockcroft-Gault)

* CTCAE grade (Gr) \>= 2 hearing loss

* CTCAE Gr \>= 2 neuropathy

Patients must not have received prior systemic therapy for their advanced cancer; prior intravesical therapy completed 4 weeks prior to enrollment and adjuvant/neoadjuvant chemotherapy completed more than 6 months prior to diagnosis of advanced disease are permitted

Zubrod performance status =\< 2 (Karnofsky \>= 60%)

Life expectancy of greater than 3 months

Leukocytes \>= 3,000/mcL

Absolute neutrophil count \>= 1,500/mcL

Platelets \>= 100,000/mcL

Total bilirubin \< 1.5 times the upper limit of normal (x ULN) for the institution

Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase \[SGOT\])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \[SGPT\]) =\< 3 x institutional upper limit of normal

Creatinine clearance; calculated creatinine clearance (CrCl) \>= 30 mL/min and \< 60 mL/min (Cockroft-Gault) unless the patient qualified based on hearing loss or neuropathy

Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation; should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately; men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and 4 months after completion of gemcitabine and eribulin administration

Ability to understand and the willingness to sign a written informed consent document

What this study is about