A phase I/II study examined treatment strategies for patients with pancreatic cancer and peritoneal metastasis. After assessing a combination of intravenous gemcitabine, intravenous nab‐paclitaxel, and intraperitoneal paclitaxel, the study authors concluded, “Adding intraperitoneal paclitaxel had clinical efficacy with acceptable tolerability,” and plans for a phase III trial are now underway.
“Favourable clinical effects of intraperitoneal paclitaxel have been reported in clinical trials of patients with peritoneal metastasis, including those with ovarian, gastric, and pancreatic cancer,” the study authors wrote, adding, “Recently, nab‐paclitaxel combined with gemcitabine was shown to be the standard treatment option for patients with pancreatic cancer and distant metastasis.”
If staging laparoscopy or open laparotomy uncovered peritoneal dissemination or positive peritoneal cytology, patients received a peritoneal access port in the lower abdomen. Patients received intravenous nab-paclitaxel plus gemcitabine with intraperitoneal paclitaxel on days one, eight, and 15, and then they had one week of rest. This was repeated every four weeks until patients attained unacceptable toxicity, disease progression, or surgery. Surgical resection criteria were an Eastern Cooperative Oncology Group performance status of 0 or 1; marked tumor shrinkage, decrease or normalization of tumor marker levels, washing cytology via peritoneal access port turned negative (twice in a row), and disappearance of peritoneal deposits on staging laparoscopy.
The researchers assessed the frequencies of dose-limiting toxicities, with the recommended dose being established in phase I. Phase II focused on the one-year overall survival rate, with other outcomes including antitumor effects, symptom-reliving effects, safety, and overall survival.
Per the phase I results, the recommended dose of intravenous gemcitabine was 800 mg/m2, of intravenous nab-paclitaxel was 75 mg/m2, and of intraperitoneal paclitaxel was 20 mg/m2. A total of 46 patients were enrolled in phase II. The median (range) time to treatment failure was six (zero to 22.6) months. The response rate was 21 of 43, and the disease control rate was 41 of 43. Among 30 total patients, ascites disappeared in 12; among 46 total patients, cytology became negative in 12. Median survival was 14.5 months. One-year overall survival rate was 61%. Eight patients of the total cohort underwent conversion surgery; patients who underwent resection had a significantly longer survival time than those who did not undergo surgery (median survival not reached vs. 12.4 months). Thirty-five patients in the total cohort sustained grade 3 to 4 hematological toxicities, and seven patients sustained non-hematological adverse events.
The study was published in the British Journal of Surgery.
“This trial demonstrated the clinical efficacy of a chemotherapy regimen comprising intravenous gemcitabine, intravenous nab‐paclitaxel and intraperitoneal paclitaxel, with acceptable tolerability, in patients with peritoneal metastasis from pancreatic cancer. Although the clinical response and survival data did not exceed those of an S‐1‐based regimen in a previous study, this strategy represents an option for treating peritoneal disease in countries where S‐1 is not available,” the researchers summarized.
“Now, a phase 3 study to compare survival outcomes between this therapy and standard chemotherapy has been launched,” senior author Sohei Satoi, MD, of Kansai Medical University, in Japan, said in a press release.