Paclitaxel Monotherapy in Advanced Urothelial Cancer

In addition to the study reported by Friedland, another study of the use of paclitaxel in urothelial cancer was presented at ASCO. This study employed paclitaxel alone on a weekly schedule and showed it to be active in heavily pretreated, advanced urothelial cancers. It should be tested further in chemotherapy-naive patients, according to Catherine M. Broome, MD, of the Northern Virginia Oncology Group, Fairfax.

Dr. Broome reported phase II data showing an overall response rate of 10% in 31 patients with progressive regional or metastatic urothelial cancers.

Dr. Broome’s group initiated this trial after an overall response rate of 42% to single-agent paclitaxel had been reported in patients with previously untreated advanced urothelial cancer.

This phase II study included 31 patients with histologically confirmed transitional cell, squamous cell, or adenocarcinoma of the urothelium. All had evidence of progressive regional or metastatic bidimensionally measurable disease.

All Previously Treated

Most patients had two or more sites of metastasis, and 45% had three or more; 65% had visceral metastases (lung, liver, or bone).

All had received one prior systemic or intra-arterial chemotherapy regimen for advanced disease. The most common (42%) was MVAC (methotrexate, vinblastine, Adriamycin, cisplatin). Forty-two percent of patients had received radiation therapy.

Prior adjuvant chemotherapy in addition to therapy for advanced disease was allowed, as was prior taxane therapy administered on a 3-week or greater schedule.

The best response to prior therapy included three complete responses and five partial responses. In addition, eight patients had stable disease, and six had disease progression. Previous response information was not available for nine patients.

Four-Week Treatment Cycle

Paclitaxel was administered at 80 mg/m² IV over 1 hour every week per 4-week cycle until disease progression or prohibitive toxicity. According to Dr. Broome, the median number of cycles delivered was 4 (range, 1 to 8) at an average weekly paclitaxel dose of 79 mg/m².

Premedication given 30 to 60 minutes prior to paclitaxel included dexamethasone (Decadron), diphenhydramine (Benadryl), and cimetidine (Tagamet).

There were three partial responses (10%), and six patients had stable disease (19%). “The three partial responses were observed in patients who had had either a complete response or a partial response to prior therapy. Response durations were 81, 112, and 147 days,” Dr. Broome said.

She reported that, overall, therapy was relatively well tolerated. Only four patients (13%) experienced significant hematologic toxicity in the form of anemia. Grade 3 neuropathy and asthenia occurred in two patients each, and one patient had grade 3 musculoskeletal toxicity (bone pain). There was no grade 4 toxicity.

“The overall response rate to weekly paclitaxel therapy in this group of previously treated patients with advanced urothelial cancer was 10%, with 3 of 31 patients achieving a partial response,” Dr. Broome said. “However, the poor prognostic characteristics of these patients should be considered, including prior chemotherapy and a high proportion of patients with visceral metastases. In addition, nearly half of all patients had three or more involved metastatic sites of disease.”

Studies of weekly paclitaxel-based combination regimens in chemotherapy-naive patients with advanced urothelial cancer are ongoing, she said.