Impact of perioperative chemotherapy on survival in patients with advanced primary urethral cancer: results of the international collaboration on primary urethral carcinoma.

BACKGROUND: To investigate the impact of perioperative chemo(radio)therapy in advanced primary urethral carcinoma (PUC). PATIENTS AND METHODS: A series of 124 patients (86 men, 38 women) were diagnosed with and underwent surgery for PUC in 10 referral centers between 1993 and 2012. Kaplan-Meier analysis with log-rank testing was used to investigate the impact of perioperative chemo(radio)therapy on overall survival (OS). The median follow-up was 21 months (mean: 32 months; interquartile range: 5-48). RESULTS: Neoadjuvant chemotherapy (NAC), neoadjuvant chemoradiotherapy (N-CRT) plus adjuvant chemotherapy (ACH), and ACH was delivered in 12 (31%), 6 (15%) and 21 (54%) of these patients, respectively. Receipt of NAC/N-CRT was associated with clinically node-positive disease (cN+; P = 0.033) and lower utilization of cystectomy at surgery (P = 0.015). The objective response rate to NAC and N-CRT was 25% and 33%, respectively. The 3-year OS for patients with objective response to neoadjuvant treatment (complete/partial response) was 100% and 58.3% for those with stable or progressive disease (P = 0.30). Of the 26 patients staged ≥cT3 and/or cN+ disease, 16 (62%) received perioperative chemo(radio)therapy and 10 upfront surgery without perioperative chemotherapy (38%). The 3-year OS for this locally advanced subset of patients (≥cT3 and/or cN+) who received NAC (N = 5), N-CRT (N = 3), surgery-only (N = 10) and surgery plus ACH (N = 8) was 100%, 100%, 50% and 20%, respectively (P = 0.016). Among these 26 patients, receipt of neoadjuvant treatment was significantly associated with improved 3-year relapse-free survival (RFS) (P = 0.022) and OS (P = 0.022). Proximal tumor location correlated with inferior 3-year RFS and OS (P = 0.056/0.005). CONCLUSION: In this series, patients who received NAC/N-CRT for cT3 and/or cN+ PUC appeared to demonstrate improved survival compared with those who underwent upfront surgery with or without ACH.

Weekly paclitaxel and carboplatin against advanced transitional cell cancer after failure of a platinum-based regimen.

OBJECTIVE: Weekly administration of paclitaxel plus carboplatin is hypothesized to be an effective second-line treatment for advanced transitional cell cancer after failure of platinum-based regimen. In this phase 2 trial, we tested this hypothesis. PATIENTS AND METHODS: Patients with advanced transitional cell cancer who showed evidence of progressive or recurrent disease after methotrexate, vinblastine, doxorubicin, and cisplatin (MVAC) therapy were eligible for this study. Weekly paclitaxel (80mg/m(2)) and carboplatin (AUC 2) were administered on days 1, 8, 15, 22, 29, and 36; the cycle was repeated every 7 wk until disease progression or intolerable toxicity (maximum 18 doses). RESULTS: Thirty-five patients entered this study. Among the 31 patients who were assessable, 10 had an objective response (overall response rate: 32.3%, 95% confidence interval, 15.8-48.7%). The median progression-free survival (PFS) and median survival times were 3.7 and 7.9 mo, respectively. Among the 22 patients who received prior MVAC therapy for metastatic disease, 36% had an objective response; their median PFS and median survival times were 4.3 and 7.9 mo, respectively; neither survival time significantly differed from the survival time of those who received prior MVAC as adjuvant setting. Toxicities were mild except one toxic death due to neutropenic sepsis. CONCLUSIONS: Weekly paclitaxel plus carboplatin was a manageable, active second-line treatment for advanced transitional cell cancer after failure of platinum-based therapy.

Phase II trial of pemetrexed as second-line therapy in patients with metastatic urothelial carcinoma.

PURPOSE: The purpose of this single-center phase II study was to determine the activity of pemetrexed administered as second-line therapy in patients with advanced urothelial carcinoma. METHODS: Patients with advanced urothelial carcinoma that had relapsed after receiving perioperative chemotherapy, or progressed on first-line chemotherapy for metastatic disease, were eligible for enrollment. Patients received pemetrexed 500 mg/m(2) every 21 days along with folic acid and vitamin B12 supplementation. RESULTS: A total of 13 patients were enrolled. An objective response was achieved in 1/12 evaluable patients for an overall response rate of 8% (90% upper limit 29%). This level of activity did not meet criteria for expansion based on the pre-defined optimal 2-stage Simon design and the trial was concluded. Treatment was generally well tolerated, however, 2/13 patients developed febrile neutropenia. Non-hematologic grade > or = 3 toxicity was rare. CONCLUSIONS: Pemetrexed as second-line therapy in advanced urothelial carcinoma is associated with modest activity. The role of this novel antifolate in chemotherapy-naïve patients warrants further investigation.

Primary carcinoma of female urethra.

The clinical and morphologic features in 29 cases of primary carcinoma of the female urethra were reviewed. Only 2 of 12 patients treated with radiotherapy are known to have failed; one is dead of disease at one year, and the other is alive with local recurrence at two years. We consider these results sufficiently satisfactory to warrant the continued use of radiotherapy in early-stage lesions, as well as in selected patients who have infiltrating carcinoma. Integrated therapy consisting of 5,000 rad/25 fractions/five weeks, followed in six weeks by radical cystourethrectomy, was used in 7 patients. The low morbidity and absence of operative mortality recommend continuation of this aggressive approach for infiltrating tumors in selected patients.