Renal Transitional Cell Carcinoma Medication
- Author: Bagi RP Jana, MD; Chief Editor: Jules E Harris, MD, FACP, FRCPC more...
The goals of pharmacotherapy are to induce remission, reduce morbidity, and prevent complications. The combination of methotrexate, vinblastine, doxorubicin (Adriamycin), and cisplatin (MVAC) is the best-studied chemotherapy regimen for upper urinary tract TCC. Durable, complete responses were obtained in only 5-10% of patients. Serious complications were encountered in 41% of patients; treatment-related mortality was 2-4%.
Gemcitabine-based combinations (gemcitabine + cisplatin or carboplatin) have activity similar to MVAC in bladder cancer but are associated with less toxicity. Some studies found the combination of gemcitabine and paclitaxel to be as effective as cisplatin-based therapies, with less nephrotoxicity.
Antineoplastic agents inhibit cell growth and proliferation.
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.
A vinca alkaloid with cytotoxic effect via mitotic arrest, vinblastine binds to a specific site on tubulin, prevents polymerization of tubulin dimers, and inhibits microtubule formation. Intrathecal (IT) administration may result in death.
Doxorubicin is an anthracycline antibiotic that causes DNA strand breakage through effects on topoisomerase II and direct intercalation into DNA, which causes DNA polymerase inhibition. This drug is both mutagenic and carcinogenic.
Cisplatin is a platinum-containing compound that exerts an antineoplastic effect by covalently binding to DNA, with preferential binding to N-7 position of guanine and adenosine. It can react with 2 different sites on DNA to produce cross-links. The platinum complex also can bind to nucleus and cytoplasmic protein.
Gemcitabine is a cytidine analog. After intracellular metabolism to its active nucleotide, it inhibits ribonucleotide reductase and competes with deoxycytidine triphosphate for incorporation into DNA.
Carboplatin is an analog of cisplatin. This is a heavy metal coordination complex that exerts its cytotoxic effect by platination of DNA, a mechanism analogous to alkylation, leading to interstrand and intrastrand DNA cross-links and inhibition of DNA replication. It binds to protein and other compounds containing an SH group. Cytotoxicity can occur at any stage of the cell cycle, but the cell is most vulnerable to the action of these drugs in the G1 and S phase. Carboplatin has the same efficacy as cisplatin but with a better toxicity profile. The main advantages over cisplatin include less nephrotoxicity and ototoxicity (not requiring extensive prehydration) and a lower likelihood of inducing nausea and vomiting; however, it is more likely to induce myelotoxicity.
Grollman AP, Shibutani S, Moriya M, et al. Aristolochic acid and the etiology of endemic (Balkan) nephropathy. Proc Natl Acad Sci U S A. 2007 Jul 17. 104(29):12129-34. [Medline].
Colin P, Koenig P, Ouzzane A, et al. Environmental factors involved in carcinogenesis of urothelial cell carcinomas of the upper urinary tract. BJU Int. 2009 Nov. 104(10):1436-40. [Medline].
American Cancer Society. Cancer Facts & Figures 2009. Accessed December 12, 2009. [Full Text].
Margulis V, Shariat SF, Matin SF, et al. Outcomes of radical nephroureterectomy: a series from the Upper Tract Urothelial Carcinoma Collaboration. Cancer. 2009 Mar 15. 115(6):1224-33. [Medline].
Park J, Ha SH, Min GE, et al. The protective role of renal parenchyma as a barrier to local tumor spread of upper tract transitional cell carcinoma and its impact on patient survival. J Urol. 2009 Sep. 182(3):894-9. [Medline].
Novara G, De Marco V, Dalpiaz O, et al. Independent predictors of contralateral metachronous upper urinary tract transitional cell carcinoma after nephroureterectomy: multi-institutional dataset from three European centers. Int J Urol. 2009 Feb. 16(2):187-91. [Medline].
Todenhofer T, Hennenlotter J, Esser M, et al. Combined application of cytology and molecular urine markers to improve the detection of urothelial carcinoma. Cancer Cytopathol. 2012 Nov 21. [Medline].
Vikram R, Sandler CM, Ng CS. Imaging and staging of transitional cell carcinoma: part 2, upper urinary tract. AJR Am J Roentgenol. 2009 Jun. 192(6):1488-93. [Medline].
Jeong YB, Kim HJ. Is It Transitional Cell Carcinoma or Renal Cell Carcinoma on Computed Tomography Image?. Urology. 2011 Dec 21. [Medline].
Rastinehad AR, Ost MC, Vanderbrink BA, et al. A 20-year experience with percutaneous resection of upper tract transitional carcinoma: is there an oncologic benefit with adjuvant bacillus Calmette Guerin therapy?. Urology. 2009 Jan. 73(1):27-31. [Medline].
Demery ME, Thezenas S, Pouessel D, Culine S. Systemic chemotherapy in patients with advanced transitional cell carcinoma of the urothelium and impaired renal function. Anticancer Drugs. 2012 Feb. 23(2):143-8. [Medline].
Pak RW, Moskowitz EJ, Bagley DH. What is the cost of maintaining a kidney in upper-tract transitional-cell carcinoma? An objective analysis of cost and survival. J Endourol. 2009 Mar. 23(3):341-6. [Medline].
Straub J, Strittmatter F, Karl A, Stief CG, Tritschler S. Ureterorenoscopic biopsy and urinary cytology according to the 2004 WHO classification underestimate tumor grading in upper urinary tract urothelial carcinoma. Urol Oncol. 2012 Jan 31. [Medline].
Hsueh TY, Huang YH, Chiu AW, et al. A comparison of the clinical outcome between open and hand-assisted laparoscopic nephroureterectomy for upper urinary tract transitional cell carcinoma. BJU Int. 2004 Oct. 94(6):798-801.
Kawauchi A, Fujito A, Ukimura O, et al. Hand assisted retroperitoneoscopic nephroureterectomy: comparison with the open procedure. J Urol. 2003 Mar. 169(3):890-4; discussion 894. [Medline].
Ong AM, Bhayani SB, Pavlovich CP. Trocar site recurrence after laparoscopic nephroureterectomy. J Urol. 2003 Oct. 170(4 Pt 1):1301. [Medline].