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.