MP63-07: Sequential Endoluminal Doxorubicin and Gemcitabine Alternating with Sequential Mitomycin and Docetaxel for Multi-Failure Non-Muscle Invasive Urothelial Carcinoma of the Upper and Lower Urinary Tracts
Introduction: Sequential intravesical gemcitabine and docetaxel (Gem/Doce) has shown over 50% 2-year high-grade (HG) recurrence free survival in patients with BCG-unresponsive non-muscle invasive urothelial carcinoma (NMIUC) of the bladder. For those who recur, further bladder-sparing therapies are needed, particularly when cystectomy is refused or precluded. We report outcomes of patients treated with a novel regimen of sequential doxorubicin and gemcitabine alternating with sequential mitomycin C and docetaxel (Quad Chemo) as a rescue therapy for patients with recurrent high-grade (HG) NMIUC. Methods: We retrospectively reviewed 27 patients (37 treated units; 27 lower tract, and 10 upper tract) treated with Quad Chemo from December 2007 to February 2021. Patients received 8 induction endoluminal instillations of sequential 50 mg doxorubicin and 1 g gemcitabine alternating weekly with sequential 40 mg mitomycin C and 37.5 mg docetaxel. Alternating monthly maintenance treatment was administered up to 24 months if disease free at 3-month surveillance. The primary outcome was recurrence-free survival (RFS) defined as no disease on bladder/upper tract wash cytology or for-cause biopsies. Progression events included development of muscle-invasive or metastatic disease and any death due to bladder cancer. Adverse events were reported per CTCAE v.5. Results: Median follow-up was 36 months. Patients with lower tract disease had a median of 3 prior inductions and upper tract 1 prior induction course. Stage at induction was pure CIS or positive cytology in 29 (78%) units, CIS + papillary in 5 (14%), and pure HG papillary in 1 (2.7%). Two (5.4%) upper tract units received Quad Chemo following a suspicious cytology. Among all treated units, the 2-year RFS rate was 38%. If disease-free at first follow-up, median duration of response was 30 months. The 2-year cystectomy-free, progression-free, and cancer-specific survival rates were 82%, 87%, and 96%, respectively. Regarding adverse events, 7.4% (2/27) of patients had a grade 3 event, including bladder stone development, bladder ulceration, and de-novo hydronephrosis. 67% (18/27) of patients experienced a grade 1-2 event. Induction treatment was ended in 11% (3/27) of patients due to side effects. Conclusions: Quad Chemo shows efficacy in a heavily pretreated HG NMIUC cohort but with a more severe side effect profile. Further prospective evaluation is needed for this regimen and to evaluate the boundaries of intravesical therapy. SOURCE OF Funding: This work was supported by the John & Carol Walter Family Foundation and the Cancer Center Support Grant.
