Efficacy of Bidirectional Paclitaxel plus Capecitabine or Nilotinib for Peritoneal Carcinomatosis: A Single Institution Analysis of Two Phase II Clinical Trials

BACKGROUND: The efficacy of locoregional therapy with intraperitoneal (IP) drug delivery plus systemic chemotherapy for peritoneal carcinomatosis is understudied. We investigated progression-free survival (PFS) and overall survival (OS) in patients with peritoneal carcinomatosis from gastric, appendiceal, or small bowel adenocarcinoma who received intravenous (IV) and IP paclitaxel plus capecitabine or nilotinib. METHODS: Two separate single-institution phase II clinical trials evaluating IP and IV paclitaxel therapy plus capecitabine or nilotinib for peritoneal carcinomatosis were analyzed. Enrolled patients with peritoneal-only metastatic gastric cancer received IP and IV paclitaxel plus capecitabine. Participants with peritoneal carcinomatosis from appendiceal, gastric, or small bowel adenocarcinoma received IP and IV paclitaxel plus nilotinib. RESULTS: Twelve patients with a median age of 46 years (range 38-64) received bidirectional paclitaxel plus capecitabine. Median overall PFS and OS was 5.3 months (95% confidence interval [CI] 1.5-13.3) and 12.5 months (95% CI 4.7-14.7), respectively. Seven patients with peritoneal carcinomatosis from appendiceal, gastric, or small bowel adenocarcinoma with a median age 59 years (range 46-69) received bidirectional paclitaxel plus nilotinib. Median PFS and OS was 3.6 months (range 2.6-6.6) and 8.3 months (range 2.8-10.2), respectively, for those receiving bidirectional paclitaxel plus nilotinib. Adverse events (AEs) were common; grade 3-5 AEs occurred in 90.1% (10/11) of participants receiving IP/IV paclitaxel plus capecitabine and 100% (7/7) of patients receiving IP/IV paclitaxel plus nilotinib. There was no extra-peritoneal disease progression, suggesting tumor confinement among all participants. CONCLUSIONS: Bidirectional paclitaxel-based chemotherapy plus capecitabine may delay progression of gastric adenocarcinoma with peritoneal-only metastasis. Bidirectional paclitaxel-based chemotherapy plus nilotinib was associated with mostly stable peritoneal disease in this small, heterogenous cohort. Bidirectional paclitaxel combinations are feasible and may have a role in therapy for disease stabilization in individuals with peritoneal carcinomatosis.