NIPS shows potential in gastric cancer with peritoneal metastasis

A neoadjuvant intraperitoneal and systemic chemotherapy (NIPS) comprising a triplet regimen of intraperitoneal docetaxel combined with intravenous cisplatin and oral S-1 was well tolerated with promising efficacy in patients who had gastric cancer with peritoneal carcinomatosis (PC), according to a presentation during the International Society for the Study of Pleura and Peritoneum (ISSPP) 2019 Congress held recently in Singapore.

“Treatment of peritoneal disease remains an unmet need,” said Dr Lam Ka On from the Queen Mary Hospital, Hong Kong. In advanced gastric cancer, PC is common but outcomes remain poor with the conventional treatment of systemic therapy.

Although a triplet regimen of intravenous docetaxel, cisplatin and 5-fluorouracil (FU) has been shown to be effective in the V325 study, this comes at the expense of significant toxicity. [J Clin Oncol 2006;24:4991-4997]

“NIPS is a new bidirectional induction chemotherapy for treatment of PC from gastric cancer [and] various phase I/II clinical trials have shown promising efficacy of this approach [with potentially less systemic toxicity],” said Lam. “Patients with good response to NIPS may undergo subsequent gastrectomy.” [J surg Oncol 2012;105:38-42]

In a feasibility study of intraperitoneal docetaxel + intravenous cisplatin + oral S-1, 12 patients (median age 57.5 years, eight female) with histologic confirmed gastric cancer and peritoneal metastasis were enrolled to undergo treatment with the triplet regimen in Queen Mary Hospital. Intraperitoneal docetaxel was administered over 1 hour on day 1 Q3W, intravenous cisplatin at a fixed dose of 60 mg/m² on day 1, and oral S-1 twice daily according to body surface area on day 1–14 Q3W. [Ann Oncol 2018;doi:10.1093/annonc/mdy151.065]

Unlike the V325 study, S-1 was used in place of 5-FU. The basis for choosing S-1 (a combination drug comprising tegafur/gimeracil/oteracil) in the regimen was its potentially better efficacy in diffuse type histology, which according to Lam is common among Asian patients. Also, the pharmacokinetic aspect of the S-1 formulation allows the concentration of 5-FU to be enhanced and retained in the peritoneum for its cell-killing effect, he added.  

Of the 11 patients who completed three cycles of treatment, five (45.5 percent) showed no gross PC at restaging diagnostic laparoscopy. These five cases underwent gastrectomy with D2 lymphadenectomy. Those who had residual PC continued with chemotherapy and no gastrectomy was performed. 

For the overall population, the median progression-free survival (PFS) was 11 months and the median overall survival (OS) was 15 months.  

When the analysis was stratified by gastrectomy, patients who underwent gastrectomy had significantly prolonged PFS (median, 21 vs 6 months; p=0.025) and a trend towards improved OS (median, 26 vs 13 months; p=0.052) compared with those who did not undergo gastrectomy.

All patients, except one, managed to complete all three cycles of treatment. During cycles 2 and 3, four patients delayed treatment cycle and one patient required dose reduction. Leukopenia was the most frequently reported haematological toxicity of grade ≥3 while hyponatraemia was the most common nonhaematological toxicity. There was no report of treatment-related death.

“Intraperitoneal docetaxel combined with intravenous cisplatin and oral S-1 was well-tolerated with promising efficacy for gastric cancer with PC,” concluded Lam.