Nab-paclitaxel Plus Gemcitabine as First-line Therapy for Cisplatin-ineligible or Cisplatin-incurable Advanced Urothelial Carcinoma

KEY POINTS:

Inclusion Criteria:

1. Histologically confirmed diagnosis of urothelial carcinoma (UC) that is either metastatic (any N+ M1) or locally advanced and unresectable (T4bN0). A component of urothelial (transitional cell) carcinoma is required.
2. Two groups of patients are eligible:

   1. Poor candidates for cisplatin-based chemotherapy based on the presence of ≥ 1 the following:

      * Glomerular filtration rate of 30-60 ml/min (Cockcroft-Gault formula)
      * ECOG performance status score of 2
      * Hearing loss (trouble communicating with hearing aids or hearing loss at ≤ 3 KHz)
      * Grade ≥3 heart failure
      * Age ≥80 years
      * Other concurrent illness which may make the patient a poor candidate for receiving cisplatin.

      Note: Enrollment of patients with 2 or more of these criteria should occur only after careful consideration by the treating physician regarding the patient's ability to tolerate combination chemotherapy.

      OR
   2. Poor prognosis and defined as cisplatin-incurable due to the presence of metastasis to at least one visceral site (these patients are not required to have any of the cisplatin-ineligibility criteria).

      * ECOG performance status score of 0, 1, or 2.
3. Measurable or evaluable disease per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1.
4. Patients with brain metastases are allowed if treatment was completed at least 4 weeks prior to study treatment, neurologic symptoms are minimal and stable during the preceding 4 weeks, and maintenance dexamethasone is not required.
5. Adequate hematologic, liver and kidney function.
6. Willingness and ability to comply with study requirements and give written informed consent.

Exclusion Criteria:

1. Previous systemic chemotherapy for UC with the exception of perioperative (neoadjuvant or adjuvant) treatment or treatment with concurrent chemoradiation for locally advanced disease. All of these treatments must have been completed more than 1 year previously.
2. Presence of small-cell or sarcomatoid component in tumor histology.
3. Women who are pregnant or breast-feeding.
4. Major surgical procedures ≤28 days of beginning study drug, or minor surgical procedures ≤7 days. No waiting required following port-a-cath placement.
5. Cardiac diseases currently or within the last 6 months:
6. Inadequately controlled hypertension.
7. Currently receiving treatment with therapeutic doses of warfarin sodium. (A maximum daily dose of 1 mg will be permitted for port line patency. Low molecular weight heparin is allowed.)
8. Serious active infection at the time of treatment, or another serious underlying medical condition that would impair the ability of the patient to receive protocol treatment.
9. Known diagnosis of human immunodeficiency virus, hepatitis B or hepatitis C (screening for these diseases is not required.).
10. Presence of other active cancers, or history of treatment for invasive cancer ≤5 years previously. Patients with Stage I cancer who have received definitive local treatment and are considered unlikely to recur are eligible. All patients with previously treated in situ carcinoma (i.e., non-invasive) are eligible, as are patients with history of non-melanoma skin cancer.