Treatment of Metastatic Upper Tract Urothelial Cancers

141                 Treatment of Metastatic Upper Tract Urothelial Cancers


Jose Pacheco, Saleha Sajid, and Teresa Gray Hayes


Urothelial carcinoma (UC) of the upper tract is a rare, aggressive urologic cancer with a tendency to metastasize early. Level 1 evidence from a prospective randomized controlled trial (RCT) is not available given its rarity, and treatment strategies are adapted from metastatic UC of the bladder (Chapter 26). The two first-line chemotherapy options in patients with good organ function and performance status (Eastern Cooperative Oncology Groups Performance Status 0 to 1) are gemcitabine plus cisplatin (GC) and dose-dense methotrexate + vinblastine + adriamycin + cisplatin (ddMVAC) (Table 21.1). However, a direct comparison between GC and ddMVAC has not been done in a randomized trial. The phase 3 multicenter RCT that suggested similar survival and a more tolerable side effect profile for GC (significantly less grade 3/4 neutropenia, neutropenic fever, neutropenic sepsis, mucositis, and alopecia) was comparing it to standard MVAC (sMVAC) (1). The reasons why ddMVAC is preferred in clinical practice over sMVAC are 3-fold based on the results of an RCT in metastatic UC of the bladder:

  i.  ddMVAC demonstrated an improved overall response rate (ORR) compared to sMVAC (64% vs. 50%) and improved progression free survival (PFS) (9.5 months vs. 8.1 months)

 ii.  While there was no significant difference in median overall survival (OS), the 5-year OS was significantly better for ddMVAC at 21.8% versus 13.5% with sMVAC

iii.  ddMVAC was better tolerated than sMVAC with less grade 3 to 4 leukopenia, neutropenic fever, and mucositis (2)


142Table 21.1 First-Line Regimens for Advanced Urothelial Carcinoma

Cisplatin eligible Cisplatin ineligibleab If Her2 positive

a.  ddMVAC

b.  GC

a.  Carboplatin-based regimens

b.  Taxol-based regimens

c.  Single agent chemotherapy regimens

d.  Clinical trial

e.  Can consider atezolizumab, nivolumab, or another immune checkpoint inhibitor*

a.  Can consider clinical trials of Her2 targeting agent alone or in combination with chemotherapy

ddMVAC, dose-dense methotrexate + vinblastine + adriamycin + cisplatin; GC, gemcitabine + cisplatin.

aIneligibility criteria for cisplatin include: creatinine clearance less than 60 mL/min by the Cockcroft Gault formula, ECOG PS ≥ 2, grade ≥ 2 hearing loss, and grade ≥ 2 peripheral neuropathy.

bFor select patients with creatinine clearance between 45 and 59 mL/min by the Cockcroft Gault formula, one can consider split dose cisplatin-based regimens.

*Immune checkpoint inhibitors have not been approved at the time of this publication for first-line therapy in cisplatin ineligible patients with metastatic urothelial cancer. However, several of them are undergoing Federal Drug Administration review for this indication and are likely to be approved soon.

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Nov 24, 2018 | Posted by in UROLOGY | Comments Off on Treatment of Metastatic Upper Tract Urothelial Cancers

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