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Nab-Paclitaxel Continues to Be Explored in Advanced Urothelial Cancer

Jason M. Broderick @jasoncology
Published: Thursday, Jan 03, 2013
Dr Srikala Sridhar

Srikala Sridhar, MD, MSc, FRCPC

The rapid growth in available therapies for genitourinary cancers has not extended to urothelial cancer. “Unlike prostate cancer and kidney cancer, in which there has been a remarkable number of new drugs approved, urothelial cancer has largely lagged behind in terms of drug development,” according to Srikala Sridhar, MD, MSc, FRCPC. At the 2012 Chemotherapy Foundation Symposium, Sridhar discussed how nab-paclitaxel might offer some hope for patients with advanced urothelial cancer.

Cisplatin-based combination regimens are the current standard of care for patients developing or presenting with metastatic urothelial disease; however, despite high response rates with these treatments, the median survival time is only 12 to 14 months.

There are no standard second-line treatments for urothelial cancer. In single-agent trials in this setting, the median survival time has been 5 to 10 months (Table). “Second-line urothelial cancer remains a major unmet medical need,” said Sridhar, medical oncologist, Princess Margaret Hospital, head of GU Medical Oncology Site Group, and assistant professor of Medicine, University of Toronto, Canada.

Taxanes, and specifically paclitaxel, have been the most commonly used drugs in the second-line setting, according to Sridhar. Although taxanes are well tolerated, “They require steroid premedication to prevent hypersensitivity, mostly due to the solvent cremaphor in which the taxanes are dissolved,” said Sridhar. Nab-paclitaxel, an albumin-bound nanoparticle formulation of paclitaxel, is solvent-free and thus does not require steroid premedication. Another advantage with nab-paclitaxel is that its infusion times are shorter. Based on the lack of treatment options and the established tolerability of nab-paclitaxel, Sridhar led a trial that examined the drug as a secondary treatment for urothelial cancer (ASCO GU 2011; Abstract 241).

Sridhar et al’s phase II trial involved 48 patients (median age, 66 years) with metastatic urothelial carcinoma who had progressed during or after first-line cisplatin-based chemotherapy. Prior taxane treatment was not allowed. Eighty-three percent of patients were male, 83% had an ECOG performance status of 0 to 1, 73% had visceral/bone metastases, and 53% had prior platinum response.

Patients received 260 mg/m2 of nab-paclitaxel intravenously every 3 weeks. The median number of cycles administered was six. Dose reductions were required in 33% of patients, but were primarily due to fatigue or neuropathy.

In 47 evaluable patients, the rates of partial response and stable disease were 32% and 21%, respectively. Forty-seven percent of patients had progressive disease. Median progression-free survival (PFS) was 6 months, and median overall survival (OS) was 10.8 months. As shown in the Table, the nab-paclitaxel efficacy data compare well with other single agents tested in the second-line setting.

Table. Single-Agent Second-Line Trials in Advanced Urothelial Cancer

Trial Regimen Phase N Response Rate TTP (Months) Median Survival
Lorusso 1998 Gemcitabine II 35 23% 3.8 5
Albers 2002 Gemcitabine II 30 11% 4.9 8.7
Vaughn 2002 Paclitaxel II 31 10% 2.2 7.2
Pronzato 1997 Ifosfamide II 20 5% NR NR
Witte 1997 Ifosfamide II 56 20% 2.5 5.5
McCaffrey 1997 Docetaxel II 20 13% NR 9
Sweeney 2006 Pemotrexed II 47 28% 2.9 9.6
Dreicer 2007 Epothilone B II 45 12% 2.7* 8
Bellmunt 2009 Vinflunine III 370 9% 3.0* 6.9
Sridhar 2011 nab-Paclitaxel III 47 32% 6.0* 10.8

*Progression-free survival. TTP indicates time to progression.




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