Second-line chemotherapy using taxane in patients with advanced gastric cancer who presented with severe peritoneal metastasis: A multicenter retrospective study

Background Individuals with advanced gastric cancer (AGC) who present with severe peritoneal metastasis (SPM) have poor prognosis, and the need to improve treatment for such condition and survival time is not met. Moreover, there are only few data about the second-line treatment for patients with such condition. Methods This retrospective study included patients receiving taxane-based second-line chemotherapy at three institutions in Japan between 2010 and 2016. Patients with AGC who present with SPM were included if they had massive ascites and/or inadequate oral intake requiring intravenous nutritional support. The efficacy and safety of the treatment were evaluated. Results In the present study, 43 (40%) of 108 patients had an Eastern Cooperative Oncology Group Performance Status score > 2, and the median serum albumin level of the patients was 3.3 g/mL. Ramucirumab was used in combination with paclitaxel in 21 patients. The median overall survival (OS) and progression-free survival (PFS) were 5.1 and 2.8 months, respectively. Inadequate oral intake was considered a negative prognostic factor of both OS and PFS in the multivariate analysis. Three treatment-related deaths were observed, which include those attributed to febrile neutropenia, gastrointestinal perforation, and pneumonitis. Common grade > 3 adverse events were neutropenia (35%), leukopenia (30%), anemia (24%), and anorexia (16%). We observed febrile neutropenia in 8% and gastrointestinal perforation in 4% of patients, and such conditions were primarily observed in patients with inadequate oral intake. Conclusions Taxane-based second-line chemotherapy was effective and safe for patients with AGC who present with SPM. Attention must be provided when treating patients with inadequate oral intake as they are likely to have short prognosis and serious toxicities.

Fluoropyrimidine (F) alone versus F plus platinum (P) as first-line chemotherapy in patients (pts) with advanced gastric cancer (AGC) and severe peritoneal metastasis (SPM): A multicenter observational study.

121 Background: The standard 1st-line chemotherapy for AGC pts with SPM has not been established. F alone is generally used for their treatment because of difficulty of hydration for dosing of cisplatin (CDDP) in pts with massive ascites, and has shown limited efficacy. It is unclear whether a combination of F and P (CDDP or oxaliplatin): FP improves their clinical outcome. We therefore investigated the efficacy and safety of FP in comparison with F alone. Methods: This retrospective study comprised of AGC pts with SPM and HER2 negative or unknown tumors who received FP or F as 1st-line chemotherapy between Jul 2010 and Sep 2016 at 6 institutions in Japan. SPM was defined as having massive ascites and/or inadequate oral intake requiring intravenous nutrition support. Overall survival (OS), progression-free survival (PFS), response rate of ascites, improvement rate of oral intake, and safety were compared between two treatment groups. Results: A total of 129 pts (64 in FP group, 65 in F group) were included. Patient characteristics (FP vs F) were as follows: median age, 62 vs 67; PS 0/1/2/3/4 (%), 6/64/25/3/2 vs 8/42/42/8/0; massive ascites/inadequate oral intake/both (%), 61/25/14 vs 35/29/35; number of metastatic sites 1-2/3-5 (%), 77/23 vs 78/22; median serum albumin level (g/ml), 3.1 vs 3.1. OS was significantly longer in FP group than F group (median, 9.0 vs 5.0 months; HR 0.56, 95%CI 0.39-0.82; log-rank p < 0.01); it remained significant upon multivariate analysis adjusting for prognostic variables (HR 0.48, 95% CI 0.32-0.73, p < 0.01). Pts in FP group had significantly better PFS in both uni- and multivariate analyses (median, 4.3 vs 2.3 months; HR 0.44, p < 0.01 and HR 0.40, p < 0.01, respectively). Response rate of ascites (51% vs 17%) and improvement rate of oral intake (64% vs 43%) also were better in FP group (p < 0.01 and p = 0.09, respectively). Toxicities were tolerable in both groups, but grade ≥3 neutropenia was more frequent in FP group (36% vs 11%). Conclusions: FP showed significantly better efficacy than F alone, and it could be a promising option as 1st-line treatment for AGC pts with SPM.

Exploratory study of intraperitoneal paclitaxel plus mFOLFOX6 for gastric cancer patients with peritoneal metastasis and inadequate oral intake.

TPS222 Background: Systemic chemotherapy with oral fluoropyrimidine and platinum is recommended for the first-line treatment for unresectable or recurrent gastric cancer in Japan. However, some patients with severe peritoneal metastasis cannot take oral medications because of obstruction or dysfunction of the gastrointestinal tract. FOLFOX is regarded as one of the candidates for the standard of care for gastric cancer, and is now being evaluated in clinical trials. Intraperitoneal (IP) paclitaxel (PTX) provides sustained high local concentrations, and its efficacy has been shown in ovarian and gastric cancer. We developed a regimen combining IP PTX with S-1/PTX, and the phase III trial comparing with S-1/cisplatin suggested efficacy of this regimen. Therefore, we designed a regimen combining IP PTX with mFOLFOX6, and started an exploratory study in gastric cancer patients with peritoneal metastasis and inadequate oral intake. Methods: This is a prospective, multicenter, single-arm phase I/II study. Eligibility criteria include: pathologically proven unresectable or recurrent gastric adenocarcinoma; peritoneal metastasis; inadequate oral intake; adequate bone marrow function; acceptable liver and renal function; ECOG performance status of 0-2 and age between 20-80 years. Patients undergo diagnostic laparoscopy and are implanted with an IP port in the subcutaneous space of the lower abdomen, with a catheter placed in the pelvic cavity. mFOLFOX6 is administered bi-weekly, and IP PTX 20 mg/m2 is administered through an IP port on days 1, 8 and 15. The treatment course is repeated every 4 weeks until disease progression or unacceptable toxicity. The primary endpoint is the 1-year overall survival rate. Secondary endpoints are progression free survival, time to treatment failure, response rate, negative conversion rate on peritoneal cytology and safety. Twenty medical institutions from all over Japan participate in this study, and 34 patients are to be enrolled in two years. Toxicity will be evaluated in the early stage, and the protocol will be reconsidered and revised if all of the first 3 or more than 2 of the first 6 patients develop dose-limiting toxicities. Clinical trial information: UMIN000019206.