Phase III study of intraperitoneal paclitaxel plus s-1/paclitaxel compared with s-1/cisplatin in gastric cancer patients with peritoneal metastasis: PHOENIX-GC trial.

4529 Background: Intraperitoneal (IP) chemotherapy is a promising treatment option for gastric cancer with peritoneal metastasis. Although a phase III study failed to show a statistically significant superiority of IP paclitaxel (PTX) combined with S-1 and intravenous PTX over S-1/cisplatin (SP), the standard of care as a first-line treatment in Japan, the sensitivity analysis suggested clinical efficacy of the IP PTX. Thus, attempts to combine IP PTX with other systemic therapies with higher efficacy have been warranted. After a dose-finding study, we sought to explore efficacy of a new regimen that combined IP PTX with SP. Methods: Gastric cancer patients with peritoneal metastasis confirmed by diagnostic imaging, laparoscopy or laparotomy were enrolled in the phase II multi-institutional prospective trial. In addition to the established SP regimen (S-1 administered orally at a dose of 80 mg/m2 bid for 21 days followed by a 14-day rest and cisplatin administered intravenously at a dose of 60 mg/m2 on day 8), IP PTX was administered on days 1, 8 and 22 at a dose of 20 mg/m2. The primary endpoint is overall survival (OS) rate at one year after treatment initiation. Secondary endpoints are progression free survival (PFS), response rate and toxicity. Results: Fifty-three patients were enrolled and fully evaluated for OS and toxicity. The median number of courses was 7 (range 1-20). The 1-year OS rate was 74% (95% CI, 60-83%). The median survival time was 19.4 months (95% CI, 16.7 months-). The 1-year PFS rate was 57% (95% CI, 42-69%). The overall response rate was 20% (95% CI, 1-72%) in 5 patients with target lesions. Cancer cells ceased to be detected by peritoneal cytology in 23 (64%) of 36 patients. Fourteen (26%) patients underwent gastrectomy after response to chemotherapy. The incidences of grade 3/4 hematological and non-hematological toxicities were 43% and 47%, respectively. The frequent grade 3/4 toxicities included neutropenia (23%), anemia (29%), diarrhea (13%) and anorexia (17%). Intraperitoneal catheter and implanted port-related complications were observed in 4 patients. There was 1 treatment-related death. Conclusions: IP PTX combined with SP is well tolerated and active in gastric cancer patients with peritoneal metastasis. Clinical trial information: UMIN000023000 .

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Phase III study of individualized intraperitoneal/intravenous/oral chemotherapy compared with standard intravenous/oral chemotherapy in patients with advanced gastric cancer.

Journal of Clinical Oncology ◽

10.1200/jco.2017.35.15_suppl.4021 ◽

2017 ◽

Vol 35 (15_suppl) ◽

pp. 4021-4021

Author(s):

Yang Yang ◽

Jia Wei ◽

Juan Du ◽

Lixia Yu ◽

Hanqing Qian ◽

...

Keyword(s):

Gastric Cancer ◽

Mrna Expression ◽

Advanced Gastric Cancer ◽

Cancer Patients ◽

Response Rate ◽

Predictive Biomarkers ◽

Oral Chemotherapy ◽

Phase Iii ◽

Phase Iii Study ◽

Gastric Cancer Patients

4021 Background: Tumor mRNA expression levels may have a promising role as potential predictive biomarkers for chemotherapy. Intraperitoneal (IP) chemotherapy provides sustained high local concentrations, and its efficacy has been shown in ovarian cancer and gastric cancer patients with peritoneal metastasis. We developed a regimen combining IP/intravenous(IV)/oral chemotherapy for the treatment of advanced gastric cancer patients with individualized chemotherapeutics according to mRNA expression. This multicenter phase III study evaluated the efficacy of individualized multi-route chemotherapy compared to standard systemic chemotherapy. Methods: Eligibility criteria included pathologically confirmed advanced gastric adenocarcinoma, and no prior chemotherapy. Patients were randomized 3:1 to an individualized arm (IN) and standard arm (ST). Randomization was stratified by center. Patients in individualized arm first underwent mRNA expression (BRCA1/TOPO1/TS) to choose sensltive chemotherapeutics from oxaliplatin/cisplatin/docetaxel/irinotecan/S-1 and then received individualized IP/IV/oral chemotherapy. The primary endpoint was overall survival (OS). Secondary endpoints were response rate, progression-free survival (PFS), and safety. Results: Between April 2013 and December 2015, 231 patients were enrolled, and 218 patients were included in the efficacy analysis. Baseline patient characteristics were balanced between the two arms. The median OS for IN and ST were 16.3 and 14.1 months, respectively (adjusted hazard ratio [aHR] 0.77, 95% confidence interval [CI] 0.61-0.98, p < 0.05). The overall response rate was 44.0% in the IN arm, and 33.9% in the ST arm (p < 0.05). Both regimens were tolerable. Conclusions: The primary analysis showed the statistical superiority of the individualized multi-route regimen. It suggested clinical efficacy of this regimen in patients with advanced gastric cancer. Clinical trial information: ChiCTR-IPR-15006201.

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

Journal of Clinical Oncology ◽

10.1200/jco.2017.35.4_suppl.tps222 ◽

2017 ◽

Vol 35 (4_suppl) ◽

pp. TPS222-TPS222

Author(s):

Shuntaro Yoshida ◽

Hironori Ishigami ◽

Kei Muro ◽

Shigenori Kadowaki ◽

Yasushi Tsuji ◽

...

Keyword(s):

Gastric Cancer ◽

Cancer Patients ◽

Peritoneal Metastasis ◽

Exploratory Study ◽

Oral Intake ◽

Phase Iii ◽

Pelvic Cavity ◽

Peritoneal Cytology ◽

Gastric Cancer Patients ◽

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.

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Can Gastric Cancer Patients be Successfully Recruited for Clinical Phase III/IV and Health Outcome Studies Using Managed Physician Panels?

Value in Health ◽

10.1016/j.jval.2014.08.1761 ◽

2014 ◽

Vol 17 (7) ◽

pp. A544

Author(s):

F. Eichmann ◽

P. Potthoff ◽

C. Brown

Keyword(s):

Gastric Cancer ◽

Health Outcome ◽

Cancer Patients ◽

Outcome Studies ◽

Phase Iii ◽

Clinical Phase ◽

Gastric Cancer Patients

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Survival Benefit of Traditional Chinese Herbal Medicine (A Herbal Formula for Invigorating Spleen) in Gastric Cancer Patients with Peritoneal Metastasis

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2014/625493 ◽

2014 ◽

Vol 2014 ◽

pp. 1-6 ◽

Cited By ~ 6

Author(s):

Lu Zhao ◽

Ai-Guang Zhao ◽

Gang Zhao ◽

Yan Xu ◽

Xiao-Hong Zhu ◽

...

Keyword(s):

Gastric Cancer ◽

Herbal Medicine ◽

Cancer Patients ◽

Chinese Herbal Medicine ◽

Peritoneal Metastasis ◽

Herbal Formula ◽

First Line ◽

Traditional Chinese Herbal Medicine ◽

Chinese Herbal ◽

Gastric Cancer Patients

Objective.We evaluated the efficiency of traditional Chinese herbal medicine (a compound herbal formula for invigorating spleen) as a complementary and alternative therapy for gastric cancer patients with peritoneal metastasis.Methods.Between 2001 and 2012, 93 gastric cancer patients with peritoneal metastasis were enrolled in this study. The effect of traditional Chinese herbal medicine on their long-term outcome was investigated. Kaplan-Meier method was used to assess the difference in survival time, and Cox proportional hazards regression analysis was performed to identify independent prognostic factors.Result.First-line palliative chemotherapy plus traditional Chinese herbal medicine was performed in 47 patients and the other 46 patients received chemotherapy alone. The overall survival was different between patients with and without traditional Chinese herbal medicine (12.0 versus 10.5 months;P=0.046). According to the Cox proportional hazard model, first-line chemotherapy cycle (hazards ratio [HR] = 0.527; 95% CI = 0.323~0.860) and TCHM (hazards ratio [HR] = 0.644; 95% CI = 0.481~0.992) were selected as independent prognostic factors for survival.Conclusion.The results suggest that traditional Chinese herbal medicine could improve the prognosis of the gastric cancer patients with peritoneal metastasis.

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