Urothelial Tumors of the Renal Pelvis and Ureters Medication

Updated: Apr 07, 2023
  • Author: Kyle A Richards, MD, FACS; Chief Editor: Bradley Fields Schwartz, DO, FACS  more...
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Medication

Medication Summary

Chemotherapy and BCG are often administered intravesically. Intravesical therapy may reduce or delay the progression of cancer to a higher stage. Most commonly used chemotherapy agents are mitomycin and gemcitabine. [24]

Patients may also receive systemic chemotherapy depending on severity and recurrence of the tumors. Neoadjuvant chemotherapy may be considered for select patients with UTUC (eg, higher stage, grade tumor). Immunotherapy is used for second-line treatment.

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Antineoplastics, Antibiotic

Mitomycin pyelocalyceal (Jelmyto, Vesigel)

Mitomycin is an alkylating drug isolated from the broth of Streptomyces caespitosus. It inhibits DNA synthesis. At high concentrations of mitomycin, cellular RNA and protein synthesis are also suppressed. This formulation is for pyelocalyceal use only. It is indicated for treatment of adults with low-grade upper tract urothelial cancer (LG-UTUC).

Mitomycin

Mitomycin selectively inhibits DNA synthesis. At high concentrations of the drug, cellular RNA and protein synthesis are also suppressed. Like BCG intravesical, this formulation of mitomycin is for intravesical use.

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Biological Response Modifiers

Class Summary

These agents modify immune responses, either by enhancing or suppressing it.

BCG intravesical live (Tice BCG)

BCG intravesical contains live, attenuated mycobacteria. It is indicated for prophylaxis of primary or recurrent stage Ta and/or T1 papillary tumors following transurethral resection (TUR). Not recommended for stage TaG1 papillary tumors, unless diagnosed as high risk of tumor recurrence.

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Antineoplastics, Antimetabolite

Class Summary

These agents inhibit cell growth and proliferation. They interfere with DNA synthesis by blocking the methylation of deoxyuridylic acid.

Methotrexate

Methotrexate inhibits dihydrofolate reductase (DHFR), causing a block in the reduction of dihydrofolate to tetrahydrofolate. This inhibits the formation of thymidylate and purines and arrests DNA, RNA, and protein synthesis. It is one of the components in the MVAC regimen and is used for the treatment of urothelial carcinoma. 

Gemcitabine (Gemzar)

Gemcitabine is a pyrimidine analog. After intracellular metabolism to its active nucleotide, it inhibits ribonucleotide reductase and competes with deoxycytidine triphosphate for incorporation into DNA. Gemcitabine is used in combination with cisplatin is the preferred perioperative chemotherapy regimen for urothelial cancer.

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Antineoplastics, Vinca Alkaloid

Class Summary

Vinca alkaloids act on the M and S phases of mitosis, inhibiting microtubule formation and inhibiting DNA/RNA synthesis.

Vinblastine

A vinca alkaloid with a cytotoxic effect (as a result of causing mitotic arrest), vinblastine binds to a specific site on tubulin, prevents polymerization of tubulin dimers, and inhibits microtubule formation. It used as a treatment for urothelial carcinoma in the MVAC regimen.

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Antineoplastics, Anthracycline

Class Summary

Anthracyclines inhibit DNA and RNA synthesis by steric obstruction. They intercalate between DNA base pairs and trigger DNA cleavage by topoisomerase II.

Doxorubicin

Doxorubicin is an anthracycline antineoplastic that causes DNA strand breakage through effects on topoisomerase II and direct intercalation into DNA, which causes DNA polymerase inhibition. It used as a treatment for urothelial carcinoma in the MVAC regimen.

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Antineoplastics, Alkylating

Class Summary

Alkylating agents inhibit cell growth and proliferation. They inhibit DNA synthesis by the formation of DNA cross-links.

Cisplatin

Cisplatin is a platinum-containing compound that covalently binds to DNA, binds to the N-7 position of guanine and adenosine. It can react with 2 different sites on DNA to produce cross-links. This may interference with DNA transcription and/or replication, which may trigger cytotoxic effects.

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PD-1/PD-L1 Inhibitors

Class Summary

PDL1 is expressed on the surface of activated T cells under normal conditions. PDL1 interaction inhibits immune activation and reduces T-cell cytotoxic activity when bound. This negative feedback loop is essential for maintaining normal immune responses and limits T-cell activity to protect normal cells during chronic inflammation. Tumor cells may circumvent T-cell–mediated cytotoxicity by expressing PDL1 on the tumor itself or on tumor-infiltrating immune cells, resulting in the inhibition of immune-mediated killing of tumor cells. 

Pembrolizumab (Keytruda)

Monoclonal antibody to programmed cell death-1 protein (PD-1); blocks the interaction between PD-1 and its ligands, PD-L1 and PD-L2. Pembrolizumab is indicated as first-line treatment for locally advanced or metastatic urothelial carcinoma (UC) in patients who are not eligible for cisplatin-containing chemotherapy. It is also indicated for patients with disease progression during or following platinum-containing chemotherapy or within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy. Additionally, pembrolizumab is indicated for treatment of BCG-unresponsive, high-risk, nonmuscle invasive bladder cancer (NMIBC) with carcinoma in situ (CIS) with or without papillary tumors in patients who are ineligible for, or have elected not to undergo cystectomy. It is also indicated in combination with enfortumab vedotin for locally advanced or metastatic urothelial carcinoma in adults who are not eligible for cisplatin-containing chemotherapy. 

Nivolumab (Opdivo)

Monoclonal antibody to programmed cell death ligand-1 protein (PDL1). It blocks the interaction between PDL-1 and its ligands. It is indicated for locally advanced or metastatic urothelial carcinoma in patients who have disease progression during or following platinum-containing chemotherapy, or disease progression within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy.

Atezolizumab (Tecentriq)

Monoclonal antibody to programmed cell death ligand-1 protein (PDL1). It blocks the interaction between PDL-1 and its ligands. It is indicated for locally advanced or metastatic urothelial carcinoma in patients who are not eligible for cisplatin-containing chemotherapy, or have disease progression during or following platinum-containing chemotherapy, or disease progression within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy.

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Anti-Nectin-4 Monoclonal Antibodies

Class Summary

Nectin-4 is a cell adhesion molecule that is expressed on many solid tumors. 

Enfortumab vedotin (Padcev)

Enfortumab vedotin is an antibody-drug conjugate (ADC) composed of an anti-nectin-4 monoclonal antibody attached to the cell-killing agent, monomethylauristatin E (MMAE). Once the antibody attaches to nectin-4 that is expressed on the tumor, the complex is internalized in the lysosome, which releases MMAE. Enfortumab vedotin is indicated for locally advanced or metastatic urothelial cancer in patients who have received a PD-1/L1 inhibitor and platinum-containing chemotherapy in the neoadjuvant/adjuvant, locally advanced, or metastatic setting. It is also indicated in combination with pembrolizumab for locally advanced or metastatic urothelial carcinoma in adults who are not eligible for cisplatin-containing chemotherapy.

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FGFR Inhibitors

Class Summary

Fibroblast growth factor receptor (FGFR) regulate important biological processes including cell proliferation and differentiation, which are part of a complex signaling pathway in tumorigenesis.

Erdafitinib (Balversa)

Erdafitinib inhibits FGFR phosphorylation and signaling, and thereby, decreases cell viability in cell lines expressing FGFR genetic alterations, including point mutations, amplifications, and fusions. It is indicated for locally advanced or metastatic urothelial carcinoma that has FGFR2 or FGFR3 genetic alterations and progressed during or following at least 1 line of prior platinum-containing chemotherapy, including within 12 months of neoadjuvant or adjuvant platinum-containing chemotherapy.

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