Feasibility Trial of Methotrexate–Paclitaxel as a Second Line Therapy in Advanced Urothelial Cancer

e16058 Background: Metastatic urothelial cancer progressing on or after first-line platinum-based chemotherapy is incurable and has a very poor prognosis. There is no standard second-line therapy, but the taxanes including paclitaxel, have previously shown activity. Abraxane (ABI-007) is a novel well tolerated albumin-bound nanoparticle formulation of paclitaxel. The goal of this study was to determine the efficacy and tolerability of single agent Abraxane in the second-line metastatic urothelial cancer setting. Methods: Patients with measureable metastatic urothelial cancer, who progressed on or after first-line cisplatin based chemotherapy were enrolled onto this phase II, two-stage multicenter trial. Patients received Abraxane 260 mg/m2 intravenously every 3 weeks. Clinical evaluation, CBC and blood chemistries were performed every cycle and restaging CT scans every 2 cycles. Results: Fourteen patients have been enrolled to date. Patient demographics: M: F 12:2; mean age 64 (range 45–80); ECOG 0:1:2 4:5:5. A total of 57 cycles, avg 4 cycles/ patient (range 1–9) have been administered. There were three dose delays due to neuropathy, pain, and low neutrophil count respectively. There were two dose reductions due to fatigue and neuropathy. Most frequent adverse events (AE) were fatigue, alopecia, anorexia, cough and joint pain; the most frequent grade 3+ AE were fatigue, joint pain, hypertension, joint stiffness and back pain. Fourteen patients are currently evaluable for best response using RECIST criteria. There have been 5 partial responses (PR), 5 stable disease (SD) and 4 progressive disease (PD). Conclusions: Single agent Abraxane was well tolerated in the 2nd line, cisplatin refractory/resistant metastatic urothelial cancer setting. Preliminary efficacy results are encouraging with a clinical benefit rate of 71% (10 out of 14 evaluable pts having either SD or PR). Stage 1 response criteria have been met and accrual is ongoing to a total of 48 patients. No significant financial relationships to disclose.

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Combination therapy of low-dose gemcitabine and paclitaxel in every 4 weeks for patients with platinum-resistant urothelial cancer whose performance status is 2 or 3.

Journal of Clinical Oncology ◽

10.1200/jco.2018.36.6_suppl.462 ◽

2018 ◽

Vol 36 (6_suppl) ◽

pp. 462-462

Author(s):

Tomohiro Matsuo ◽

Yasuyoshi Miyata ◽

Yuji Sagara ◽

Kojiro Ohba ◽

Hideki Sakai

Keyword(s):

Combination Therapy ◽

Urothelial Cancer ◽

Low Dose ◽

Performance Status ◽

Control Group ◽

Second Line ◽

Second Line Therapy ◽

Line Therapy ◽

Grade 3 ◽

Experimental Group

462 Background: Platinum-based regimens are standard therapy for advanced urothelial cancer (UC). However, second-line chemotherapy is still not established. Therefore, best supportive care is often selected in patients with poor performance status (PS). In our hospital, combination therapy of low-dose gemcitabine and paclitaxel every 4 weeks is administered as second-line therapy for platinum-resistant patients with PS 2 or 3. We investigated the quality of life (QoL) and safety of our regimen in these patients. Methods: Forty-two advanced UC patients were treated with gemcitabine (700 mg/m2 on day 1) and paclitaxel (70 mg/m2 on day 1) every 4 weeks (experimental group). The QoL was evaluated using the short-form survey (SF)-36, and the data were collected on the day before the first cycle was started and 8 weeks after starting the therapy. In addition, survival analysis was performed between these patients and 30 patients who received no second-line therapy (control group). Results: In experimental group, one patient showed grade 3 anemia after the treatment. However, this patient also had severe hematuria before staring of the therapy. No patient had severe adverse events (grade 3 and higher) because of this therapy. The QoL score decreased after the therapy; however, the difference was not significant. With regard to efficacy, partial response was found in two patients, and the mean/SD survival period of the experimental group was 9.2/7.2 months. This period was significantly (P < 0.01) longer than that in the control group (5.8/2.4 months). In addition, 13 (31.0%) and 6 patients (14.3%) survived over 12 and 18 months, respectively. Conclusions: Combined therapy of low-dose gemcitabine and paclitaxel every 4 weeks was well tolerated, and the patient’s QoL was maintained after treatment. Some patients showed relatively long survival periods. We suggest that this treatment regimen is worthy of consideration as second-line therapy for patients with advanced UC with PS 2 or 3.

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