'Outside the Box': Tamoxifen for Bladder Cancer

First-Ever Clinical Trial Results

Nick Mulcahy

May 07, 2019

CHICAGO — Long established as a treatment for certain breast cancers, tamoxifen has now been studied for the first time in bladder cancer.

The generic pill belongs to a class of drugs known as selective estrogen receptor modulators (SERM), and is widely used in the treatment of estrogen receptor (ER+) positive breast cancer.

But this mechanism of action also makes it a potential candidate for the treatment of cancer in the bladder, where estrogen receptors are also present and may play a role in carcinogenesis, as suggested by preclinical and other studies, says Guilherme Godoy, MD, of Baylor College of Medicine in Houston, Texas.

Godoy presented the results of the first-ever clinical trial of tamoxifen in bladder cancer here at the 2019 American Urological Association (AUA) annual meeting.

The Baylor urologist and colleagues reported results from a phase 2, single center trial conducted in 12 evaluable patients with low- to intermediate-risk urothelial carcinoma of the bladder. Five patients (42%) had a treatment response to tamoxifen in their marker bladder lesion, which was the primary endpoint.

Of these, two (16.5%) had a complete response (CR) and three (25%) had a partial response.

The new results are "encouraging proof of concept" and a phase 3 trial is under development, with a funding application to be sent to the SWOG Cancer Research Network, Godoy told Medscape Medical News.

The small number of study patients in the current study was a result of "very strict criteria" for entry, he added.

The study subjects received 20 mg of oral tamoxifen daily for 12 weeks. The therapy was well tolerated with minimal toxicity, said the investigators.

Debasish Sundi, MD, a bladder cancer researcher at Ohio State University, Columbus, called the phase 2 results "promising," citing the efficacy and low toxicity. Asked for comment, he said he was "excited" about the prospect of a larger clinical trial.

Sundi, who was not involved with the current research, credited Godoy with completing "impressive" preclinical studies that have helped establish the concept of targeting estrogen receptors in bladder cancer.

Estrogen receptors exist both in the bladder and in bladder cancer cells, Sundi pointed out.

He congratulated the Baylor researchers for performing the novel study. "Dr Godoy and his team are thinking outside the box," Sundi told Medscape Medical News.

Response Rate Criticized

But another urologist attending AUA 2019 was not enthusiastic.

"I'm intrigued a little bit because I didn't know [tamoxifen] would produce any response," said Benjamin Davies, MD, University of Pittsburgh in Pennsylvania.

"But I don't think we will get to a place of using this drug, at least based on this data," he told Medscape Medical News. "The response rate was not robust."

Davies explained that the overall response rate may have been 42%, but that the "conventional means" of treating the disease — transurethral resection — provides a 100% complete response rate (or thereabout) because all marker lesions are removed with the surgery.

"So why would you subject patients to a treatment with a 16% complete response rate," he argued. (CR was achieved in only 2 of the 12 evaluable patients.)

"If we are going to use medicine [to treat this cancer], then I want us to approach 100% response rate," Davies said.

However, tamoxifen could have a potential role in bladder cancer treatment among patients who cannot undergo surgery or who need to delay surgery, he suggested.

More Study Details

The majority of the study participants were men, and the median age was 69 years.

There were no grade 4 or 5 adverse events, but four (8.5%) grade 3 events were recorded. Histology revealed no quantifiable fibrosis, scarring, or necrosis. Similarly, potentially relevant biomarkers (Ki-67 and cleaved PARP-1) were mostly negative across samples.

Regarding estrogen receptors (ER), ERβ was the predominantly expressed ER, with minimal ERα present. No significant differences were observed between the expression levels of the ERs in normal vs tumor or pre-treatment vs post-treatment samples, the authors noted in their meeting abstract.

The study was supported by a grant from the National Cancer Institute. The study authors have disclosed no relevant financial relationships. Sundi and Davies have disclosed no relevant financial relationships.

2019 American Urological Association annual meeting: LBA19.
Presented May 5, 2019.

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