Abdominal Chemotherapy Perfusion Effective on Treatment-resistant, Recurrent OC in Phase 2 Study

Abdominal Chemotherapy Perfusion Effective on Treatment-resistant, Recurrent OC in Phase 2 Study

Localized chemotherapy perfusion in the abdomen showed efficacy in patients with treatment-resistant and recurrent ovarian cancer, according to preliminary results of an ongoing Phase 2 clinical study. A subset of the patients showed complete cancer remission.

The study, Hypoxic isolated abdominal perfusion breaks through chemoresistance in recurrent FIGO stage IIIC and IV ovarian Cancer: experience in 143 platinum-refractory and 25 chemonaive ovarian cancer patients,” was presented at the recent 38th Congress of the European Society of Surgical Oncology (ESSO) in Budapest, Hungary.

“Increased dose or dose-dense chemotherapy for platinum-refractory ovarian cancer is limited because of increasing toxicity,” Karl R. Aigner, the study’s first author and head of the department of surgical oncology and medical director at German private hospital Medias Klinikum, noted in a press release.

An expert in regional chemotherapy, Aigner originally developed isolated liver perfusion and was the first physician worldwide to perform this method using a heart-lung machine.

To overcome treatment resistance and toxicity, Aigner and colleagues examined whether increased therapy exposure restricted to the abdomen — an approach called regional chemotherapy – could improve the outcomes of treatment-resistant patients.

The chemotherapy was administered through an isolated perfusion system coupled with a chemofiltration unit outside the body to filter the medication out of the blood. It consisted of four cycles of hypoxic (low oxygen) abdominal perfusion with chemotherapy medications — Platinol (cisplatin), Adriamycin (doxorubicin) and Mitomycin-C Kyowa (mitomycin, by Kyowa Kirin) – in four-week intervals.

The choice of Platinol and Adriamycin was based on the medications’ increased toxicity to cells under hypoxia, the scientists stated. Of the total 168 patients, 143 with recurrent disease had received prior platinum-containing therapies — 86 in FIGO stage IIIC disease and 57 in stage IV – while 25 had not been treated with any chemotherapy — 20 in stage IIIC and 5 in stage IV.

Results showed that the median survival rate of pretreated patients was 13 months for stage IIIC and 11 months for stage IV. In turn, previously untreated stage IIIC patients had a median survival rate of 16 months. No data was provided for untreated patients with stage IV disease.

Of the 79 patients who had undergone laparotomy surgery after primary treatment, complete clinical remission was found in 25% of cases and partial remission occurred in 39% of patients. The overall clinical response rate was 64%.

Complete resolution of ascites — the accumulation of fluid in the abdominal cavity — occurred in 43% of cases, and a substantial decrease was seen in an additional 19%. Toxicity and side effects were generally low.

Bone marrow suppression was mild to moderate, but severe in patients with previous third- or fourth-line chemotherapy. Fever and fatigue were the main clinical symptoms in patients with post-therapeutic tumor necrosis (cell and tissue death), who represented 15-20% of all patients.

“Isolated hypoxic abdominal perfusion with chemofiltration for patients with progressive and [platinum]-refractory stage III and IV (advanced) ovarian cancer is an effective therapy, offering comparably long survival at good quality of life,” the scientists stated.