Novel Strategy Enlists Implantable Devices to Target Residual Ovarian Tumors

Continuous low-dose cisplatin through an implantable device could be a therapeutic option in for patients with ovarian cancer.

Ovarian cancer is referred to as the silent killer because it often goes undiagnosed until its late stages. Although most women undergo surgery to remove the tumors, it is impossible to eliminate all the cancer cells due to metastasis.

To rid the body of residual tumors, patients receive 2 types of chemotherapy following surgery: intravenous delivery of paclitaxel and intravenous or intraperitoneal delivery of cisplatin. Although these methods produce better results than others, it causes significant adverse events (AEs).

Intraperitoneal chemotherapy is pumped directly into the abdomen every 3 weeks through a catheter for a total of 6 cycles. This technique has been shown to be more effective than intravenous delivery, but it is unbearable for most patients.

Several years ago, the investigators sought to develop an implantable device that could deliver cisplatin into the abdomen in large, repeated doses without the AEs.

The device is made of a drug-loaded polymer that can be inserted at the start of treatment and stay there for the full course of treatment. It can then be removed with minimally invasive surgery.

The investigators have tested proof-of-concept devices in mice, and are currently developing a version that could be tested in humans; however, more animal studies are needed before human trials can begin.

In a study published in Gynecologic Oncology, the investigators sought to examine how the size of the residual tumors impacted their response to continuous, low-dose cisplatin delivery.

“As we entered into this project, our question was how do we get the same beneficial outcomes and reduce all the side effects?” said senior author Michael Cima.

The investigators hypothesized that tumor size would have some type of effect on treatment because once they reach a certain size, the drug may not be able to penetrate the core of the tumors.

For the study, spherical ovarian cancer cell clusters that were 100 or 200 microns in diameter were grown in a lab dish and exposed to various doses of cisplatin.

Continuous low-dose cisplatin was similar to what tumors would receive from an implanted device, whereas high-dose cisplatin was similar to catheter delivery.

The results of the study showed that continuous low-dose cisplatin delivery was as efficacious against 100-micron tumor spheroids as a single high-dose. But when the continuous cisplatin dose was increased, the investigators found that 200-micron spheroids could be treated more effectively than they could with the single high-dose.

The increased dose of cisplatin delivered by an implantable device would be tolerable for patients, but not if it was administered through an abdominal catheter, according to the study.

The findings may help provide an explanation of preliminary results from a large clinical trial that found intraperitoneal cisplatin delivery was no more efficacious than intravenous chemotherapy alone, according to the authors. These findings contradicted prior results from smaller studies, which found that cisplatin delivered by catheter improved patient survival.

Cima noted that in the newer trial, surgeons admitted patients to the study based on size estimates of the tumors remaining after surgery. This subjective evaluation may have allowed patients into the study who had tumors that were too large to be treated with intraperitoneal therapy.