Phase II Study of Single Intraperitoneal Chemotherapy Followed by Systemic Chemotherapy for Gastric Cancer with Peritoneal Metastasis

Abstract Background There is no currently available treatment for peritoneal metastasis of gastric cancer. This phase II study aimed to evaluate the efficacy and safety of neoadjuvant systemic chemotherapy and hyperthermic intraperitoneal chemotherapy (HIPEC) combined with cytoreductive surgery (CRS) for the treatment of these patients. Methods Neoadjuvant chemotherapy comprised two cycles of HIPEC and four cycles of S-1 plus paclitaxel. HIPEC was administered intraperitoneally with paclitaxel (75 mg/m2). For systemic chemotherapy, paclitaxel was administered intravenously(150 mg/m2) on day 1, and S-1 was administered orally(80 mg/m2/day)on days 1–14 of a 3-week cycle. Another two cycles of HIPEC and four cycles of S-1 plus paclitaxel were administered after second diagnostic staging laparoscopy or CRS. The primary endpoints were treatment efficiency and safety; the secondary endpoint was 3-year overall survival (OS). Results A total of 40 patients were enrolled and 38 patients have been analyzed. Of these, 18 (47.4%) patients received neoadjuvant systemic chemotherapy, HIPEC and CRS (conversion therapy group), while 20 patients received only chemotherapy and HIPEC (palliative chemotherapy group). Median OS was markedly improved in the conversion therapy group (21.1 months, 95% confidence interval [CI] 16.7–25.6 months) in comparison with the palliative chemotherapy group(10.8 months, 95%CI 7.3–14.2 months, p = 0.002). After neoadjuvant systemic chemotherapy and HIPEC, a second laparoscopic exploration was performed, and the prognosis of patients with low peritoneal cancer index (PCI) (PCI < 6) was significantly better than that of patients with high PCI (PCI ≥ 6)(20.1 vs.11.3 months, p = 0.006). Conclusion Neoadjuvant systemic chemotherapy and HIPEC combined with CRS is safe and feasible, and could potentially improve the prognosis of gastric cancer patients with limited peritoneal metastasis. However, further clinical trials are still warranted. Trial registration This study has been registered with ClinicalTrials.gov as NCT02549911. Trial registration date: 15/09/2015.

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Phase II study of intraperitoneal docetaxel plus capecitabine/cisplatin for gastric cancer with peritoneal metastasis: XP+IP DOC trial.

Journal of Clinical Oncology ◽

10.1200/jco.2017.35.15_suppl.4039 ◽

2017 ◽

Vol 35 (15_suppl) ◽

pp. 4039-4039 ◽

Cited By ~ 1

Author(s):

Ryoji Fukushima ◽

Hironori Ishigami ◽

Hiroto Miwa ◽

Motohiro Imano ◽

Daisuke Kobayashi ◽

...

Keyword(s):

Gastric Cancer ◽

Cancer Patients ◽

Phase Ii ◽

Peritoneal Metastasis ◽

Phase Ii Study ◽

Median Number ◽

Peritoneal Cytology ◽

Response To Chemotherapy ◽

Grade 3 ◽

Gastric Cancer Patients

4039 Background: Intraperitoneal (IP) chemotherapy with taxanes provides sustained high local concentrations, and the efficacy of IP paclitaxel (PTX) has been shown in ovarian cancer. We previously reported the safety and efficacy of IP PTX plus systemic chemotherapy in clinical trials. Capecitabine/cisplatin (XP) is one of the standard regimens for the first-line treatment of advanced gastric cancer worldwide. We designed a new regimen combining IP docetaxel (DOC) with XP, and the recommended dose of IP DOC was determined to be 10 mg/m2 in a phase I study. A phase II study of XP plus IP DOC was performed in gastric cancer patients with peritoneal metastasis. Methods: Gastric cancer patients with peritoneal metastasis confirmed by diagnostic imaging, laparoscopy or laparotomy were enrolled. DOC was administered intraperitoneally at 10 mg/m2 on days 1 and 8. Cisplatin was administered intravenously at 80 mg/m2 on day 1, and capecitabine was administered at 1000 mg/m2 bid for 14 consecutive days, repeated every 21 days. The primary endpoint was the 1-year overall survival (OS) rate. Secondary endpoints were response rate, negative conversion rate on peritoneal cytology and safety. Results: Out of 50 patients enrolled, 48 patients received protocol treatment, and were evaluated for OS and toxicity. The median number of courses was 6 (range 1-15). The 1-year OS rate was 75% (95% confidence interval, 60-85%). The best overall response was stable disease in all the three patients with target lesions. Cancer cells ceased to be detected by peritoneal cytology in 28 (76%) of 37 patients. Nineteen patients underwent gastrectomy after response to chemotherapy. The incidences of grade 3/4 hematological and non-hematological toxicities were 42% and 48%, respectively. The frequent grade 3/4 toxicities included neutropenia (21%), leukopenia (8%), anemia (29%), anorexia (25%) and nausea (17%). Infection of the intraperitoneal port was observed in one patient. There were no treatment-related deaths. Conclusions: Combination chemotherapy of XP plus IP DOC regimen is well tolerated and active in gastric cancer patients with peritoneal metastasis. Clinical trial information: UMIN000016469.

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Phase II Study of the Effects of Laparoscopic Hyperthermic Intraperitoneal Chemotherapy (HIPEC) in Patients With Advanced Gastric Cancer

Case Medical Research ◽

10.31525/ct1-nct04107077 ◽

2019 ◽

Author(s):

Keyword(s):

Gastric Cancer ◽

Advanced Gastric Cancer ◽

Phase Ii ◽

Intraperitoneal Chemotherapy ◽

Hyperthermic Intraperitoneal Chemotherapy ◽

Phase Ii Study

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Randomized phase II study of best-available 5-fluorouracil (5-FU) versus weekly paclitaxel in gastric cancer (GC) with peritoneal metastasis (PM) refractory to 5-FU-containing regimens (JCOG0407).

Journal of Clinical Oncology ◽

10.1200/jco.2010.28.15_suppl.4052 ◽

2010 ◽

Vol 28 (15_suppl) ◽

pp. 4052-4052 ◽

Cited By ~ 9

Author(s):

H. Takiuchi ◽

H. Fukuda ◽

N. Boku ◽

Y. Shimada ◽

J. Nasu ◽

...

Keyword(s):

Gastric Cancer ◽

Phase Ii ◽

Peritoneal Metastasis ◽

Phase Ii Study ◽

Weekly Paclitaxel ◽

Randomized Phase Ii

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A phase II study of systemic chemotherapy with TS-1 combined with cisplatin followed by surgery in advanced gastric cancer (OGSG0004).

Journal of Clinical Oncology ◽

10.1200/jco.2010.28.15_suppl.e14562 ◽

2010 ◽

Vol 28 (15_suppl) ◽

pp. e14562-e14562

Author(s):

S. Okano ◽

Y. Nakane ◽

K. Inoue ◽

K. Fujitani ◽

Y. Kimura ◽

...

Keyword(s):

Gastric Cancer ◽

Advanced Gastric Cancer ◽

Phase Ii ◽

Systemic Chemotherapy ◽

Phase Ii Study

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A phase II study of induction chemotherapy with docetaxcel, cisplatin, and S-1 (DCS) for gastric cancer with peritoneal metastasis (KUGC06): Early results.

Journal of Clinical Oncology ◽

10.1200/jco.2017.35.15_suppl.e15574 ◽

2017 ◽

Vol 35 (15_suppl) ◽

pp. e15574-e15574

Author(s):

Hiroshi Okabe ◽

Hiroaki Hata ◽

Shugo Ueda ◽

Hisahiro Hosogi ◽

Shuichi Ota ◽

...

Keyword(s):

Gastric Cancer ◽

Induction Chemotherapy ◽

Phase Ii ◽

Peritoneal Metastasis ◽

Phase Ii Study ◽

R0 Resection ◽

Peritoneal Cytology ◽

Resection Rate ◽

Early Results ◽

Positive Peritoneal Cytology

e15574 Background: Although the prognosis of gastric cancer with peritoneal metastasis is extremely poor, we previously showed the significant efficacy of S-1 plus cisplatin for limited peritoneal dissemination, and favorable outcome following curative resection. We conducted a phase II study to evaluate the safety and efficacy of induction chemotherapy with docetaxel, cisplatin, and S-1 (DCS) triplet regimen for patients (pts) with gastric cancer with peritoneal metastasis. Methods: The key eligibility criteria were gastric cancer with peritoneal metastasis or positive peritoneal cytology, without any other distant metastases, age between 20 and 75 years old, PS 0 or 1, capable of oral administration, and adequate hematologic, hepatic, and renal function. Pts received three 28-day cycles of DCS (cisplatin of 60 mg/m2, docetaxel of 40mg/m2 on day 1, and S-1 of 80 mg/m2 from day 1 to 14). Following evaluation for resectability, pts received D2 gastrectomy if R0 was possible. Primary endpoint was R0 resection rate. Secondary endpoints were clinical response of peritoneal metastasis, overall response, pathological response, adverse events, progression free survival, and overall survival. Sample size was determined to have 80% power for detecting 20% improvement of R0 resection rate over 45% baseline at one-sided alpha of 0.1. Results: Between June 2011 and April 2015, 30 pts were enrolled. All pts started DCS and were included in the analysis. Three cycles of DCS (80%) were completed in 24 pts (80%). The most frequent grade 3/4 toxicity was neutropenia (60%). Complete response of peritoneal metastasis was observed in 16 pts (53%), 21 pts underwent surgery, and 14 pts achieved R0 resection (47%; 95%CI, 28-66%). When the extent of peritoneal metastasis was classified as P0CY1, P1, P2, and P3 according to the Japanese classification, R0 resection rate for each group was 63%, 60%, 46%, or 0%, respectively. Conclusions: Induction chemotherapy with DCS is safe, and could achieve R0 resection in some patients with limited peritoneal metastasis or positive peritoneal cytology. However, the efficacy seems to be similar to the conventional S-1 plus cisplatin. Clinical trial information: UMIN000004932.

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