Phase 1 trial of intraperitoneal paclitaxel in combination with intravenous cisplatin and oral capecitabine in patients with advanced gastric cancer and peritoneal metastases (IPGP study)

Abstract

Aims Gastric cancer with peritoneal involvement has a poor prognosis. Intraperitoneal (IP) paclitaxel has shown promising results in these patients. However, this approach has only been studied in the Asian population, and in combination with S‐1. We investigated the maximum tolerated dose of IP paclitaxel, with a standard chemotherapy combination, in the Australian population. Methods The study of the population included metastatic human epidermal growth factor receptor 2 (HER2) negative gastric adenocarcinoma with peritoneal involvement. Treatment included six 21‐day cycles of cisplatin (80 mg/m2 IV, day 1) plus capecitabine (1000 mg/m2 PO BD, days 1–14) plus IP paclitaxel (days 1 and 8). IP paclitaxel doses for cohort 1–3 were 10, 20, and 30 mg/m2, respectively, in a 3 + 3 standard dose‐escalation design. Results Fifteen patients were enrolled of which 6 were female and the median age was 63. Two patients developed dose‐limiting toxicities. No grade 4/5 toxicities were recorded. The maximum tolerated dose was not reached. Therefore, as defined by the study protocol, the recommended phase‐2 dose for IP paclitaxel was determined to be 30 mg/m2. The 12‐month survival rate was 46.7%, and the median survival was 11.5 months (interquartile range [IQR]: 15.3–6.9). Conclusions IP paclitaxel is safe in combination with cisplatin and capecitabine and the recommended phase‐2 dose is 30 mg/m2.

Intraperitoneal Chemotherapy for Unresectable Peritoneal Surface Malignancies

“…histology and/or cytology Paclitaxel at days 1 and 8 in 3-week cycles Paclitaxel + S-1 30 mg/m 2 20 mg/m 2 Febrile neutropenia grade 3, diarrhea grade 3 Kurita et al, 2011 [ 89 ] 4 18 Pos. histology and/or cytology Paclitaxel at days 1 and 14 in 4-week cycles S-1 90 mg/m 2 80 mg/m 2 Leukocytopenia grade 3 Vatandoust et al, 2022 [ 90 ] 4 15 Pos. histology Paclitaxel at days 1 and 8 in 3-week cycles Cisplatin + capecitabine Not reached 30 mg/m 2 Small bowel obstruction grade 3, febrile neutropenia grade 3 Kobayashi et al, 2020 [ 91 ] 4 9 Pos.…”

“…However, a retrospective analysis on intraperitoneal paclitaxel showed that the type of systemic chemotherapy did not influence overall survival [86]. In Phase I studies, intraperitoneal paclitaxel in combination with several types of systemic chemotherapy resulted in recommended doses between 20 and 80 mg/m 2 , depending on the frequency of administration [87][88][89][90][91][92][93]. The most common dose-limiting toxicities (DLTs) were hematological disorders (mostly neutropenia) or gastro-intestinal toxicities such as diarrhea or vomiting.…”