CHICAGO—A novel drug called eribulin may be effective for advanced urothelial cancer (UC), even in patients with prior adjuvant or neoadjuvant chemotherapy, according to new data presented at the American Society of Clinical Oncology annual meeting.
Eribulin is a new chemical compound discovered and developed by Tokyo-based Eisai Inc. It is a synthetic analogue of halichondrin B, which is a naturally-derived compound first isolated from the Black Pacific sea sponge. While taxanes inhibit cell division by stabilizing microtubules, eribulin is a microtubule dynamics inhibitor that arrests the cell cycle through inhibition of the growth of microtubules without interfering with microtubule shortening. A prior phase 1 study showed that eribulin and its metabolites are minimally excreted by the kidneys
Researchers at the University of Southern California (USC) in Los Angeles conducted a phase 2 trial with patients who had normal creatinine levels or calculated creatinine clearance of 60 mL/min or greater. Patients could have any histologic type of UC and no prior cytotoxic therapy for advanced disease (adjuvant or neoadjuvant therapy allowed). Eribulin 1.4 mg/m2 was administered IV on day 1 and day 8, and then once every three weeks.
Investigators enrolled 40 patients, of whom 35 had transitional cell carcinoma, three had adenocarcinoma, one had squamous cell carcinoma, and one had small cell carcinoma. The median patient age was 67 years (range 37-87 years) and 68% were male. Of the 40 patients, 72.5% received prior adjuvant or neoadjuvant chemotherapy. At the end of the study, three patients were not evaluable (two had gone off treatment due to toxicity and one died).
Of the remaining 37 patients, one had a complete response and 14 had a partial response. The response rate in patients with prior adjuvant or neoadjuvant chemotherapy was 34%. At a median follow-up of 19.8 months, the median progression-free survival was 3.9 months. The median overall survival was 9.4 months, which lead author David Quinn, MD, PhD, said is better than most single agents in this patient population. “It was a well tolerated agent as well,” said Dr. Quinn, Medical Director of USC’s Norris Cancer Hospital and Clinics at the Keck School of Medicine.
Dr. Quinn, who presented the study findings at the meeting, said 20 of the 37 patients had grade 3/4 toxicities (neutropenia and sensory neuropathy). Other non-hematologic toxicities included hyperglycemia (14 patients), hyponatremia (14 patients), alopecia (37 patients), and leg fatigue and aching (six patients).