Phase II study of weekly intravenous and intraperitoneal paclitaxel combined with S-1 for advanced gastric cancer with peritoneal metastasis

Ishigami, Hironori; Kitayama, Joji; Kaisaki, Shoichi; Hidemura, Akio; Kato, Masahiro; Otani, Kensuke; Kamei, Takao; Soma, Daisuke; Miyato, Hideyo; Yamashita, Hiroharu; Nagawa, Hirokazu

doi:10.1093/annonc/mdp260

Cited by 210 publications

(195 citation statements)

References 26 publications

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“…After a successful phase II trial with gastric cancer patients whose disease was deemed unresectable becasue of confirmed peritoneal metastasis, they conducted a randomized phase III trial with the same population to compare this hybrid regimen with the S-1 and cisplatin combination [6], the current standard of care for treatment of unresectable gastric cancer. Although survival analysis of that trial is about to be conducted, we believe that the current study remains useful to reinforce the rationale for the use of intraperitoneally administered PTX alone or in combination with other drugs to control the peritoneal disease postoperatively.…”

Section: Discussionmentioning

confidence: 99%

“…Patients with peritoneal metastases have seldom been eligible for studies that aim to evaluate new and promising drugs, because the efficacy of chemotherapeutic agents is generally elucidated through treatment of patients with measurable lesions. The efficacy of intraperitoneal administration of paclitaxel (PTX) has been suggested by some phase II trials and pharmacokinetic studies in gastric cancer [4][5][6], but less convincingly than in ovarian cancer [7], another cancer type that is commonly associated with peritoneal metastases. To date, no comparison of intraperitoneal versus intravenous administration of PTX has been attempted for gastric cancer.…”

Section: Introductionmentioning

confidence: 99%

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Feasibility of weekly intraperitoneal versus intravenous paclitaxel therapy delivered from the day of radical surgery for gastric cancer: a preliminary safety analysis of the INPACT study, a randomized controlled trial

et al. 2016

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Background Peritoneal carcinomatosis is common after curative resection of gastric cancer. Intraperitoneal administration of paclitaxel (PTX) is known to control ovarian peritoneal metastases. Patients and methods Patients with either linitis plastica or T4 cancer with high risk of peritoneal metastasis or recurrence but whose cancer was considered resectable were preregistered. After their cancer had been confirmed intraoperatively as resectable, the patients were randomized into either group A (PTX at 60 mg/m 2 intraperitoneally on the day of surgery and on days 14, 21, 28, 42, 49, and 56) or group B (PTX at 80 mg/m 2 administered intravenously by the identical schedule) before being treated by evidence-based chemotherapy. The primary end point was the 2-year survival rate. Safety, the secondary end point, was also analyzed. The study has been registered as UMIN000002957. Results Of 177 preregistered patients, 83 underwent treatment (39 by intraperitoneal administration and 44 by intravenous administration). There was no difference in patient demographics between the two groups. The incidences of surgical complications were similar between the groups, except for transient bowel obstruction observed exclusively in group A. The relative dose intensity of PTX was 81.4 % for group A and 76.3 % for group B. There was one death due to pulmonary thrombosis and a case of anaphylaxis that led to termination of the protocol treatment (group B). Other adverse events were mild and manageable. Conclusions Intraperitoneal administration of PTX from the day of gastrectomy did not result in a higher incidence of surgical complications and adverse reactions when compared with intravenous administration of PTX.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Feasibility of weekly intraperitoneal versus intravenous paclitaxel therapy delivered from the day of radical surgery for gastric cancer: a preliminary safety analysis of the INPACT study, a randomized controlled trial

et al. 2016

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“…After some pilot studies, Ishigami et al57, 58 conducted successive phase I and phase II trials to establish a combination of S‐1, i.v. paclitaxel, and i.p.…”

Section: Peritoneal Metastasismentioning

confidence: 99%

Surgery with curative intent for stage IV gastric cancer: Is it a reality of illusion?

Kodera

2018

Annals of Gastroent Surgery

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Gastric cancer with metastases outside of the regional lymph nodes is deemed oncologically unresectable. Nevertheless, some metastatic lesions are technically resectable by applying established surgical techniques such as para‐aortic lymphadenectomy and hepatectomy. At the time of compilation of the Japanese gastric cancer treatment guidelines version 4, systematic reviews were conducted to see whether it is feasible to make any recommendation to dissect both the primary and metastatic lesions with intent to cure, possibly as part of multimodality treatment. Long‐term survivors were found among carefully selected groups of patients both in prospective and retrospective studies. In addition, there is a growing list of publications reporting encouraging outcomes of gastrectomy conducted after exceptionally good response to chemotherapy, usually among patients who underwent R0 resection. This type of surgery is often referred to as conversion surgery. It is sometimes difficult to define a clear borderline between curative surgery scheduled after neoadjuvant chemotherapy and the conversion surgery. This review summarizes what we knew after the literature reviews conducted at the time of compiling the Japanese guidelines and in addition reflects some new findings obtained thereafter through clinical trials and retrospective studies. Metastases were divided into three categories based on the major metastatic pathways: lymphatic, hematogenous, and peritoneal. In each of these categories, there were findings that could provide hope for patients with metastatic disease. These findings implied that the surgical technique that we already use could become more useful upon further developments in antineoplastic agents and drug delivery.

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“…Studies have shown that i.p. administration of paclitaxel is effective in the treatment of gastric cancer with peritoneal metastasis [9][10][11].…”

Section: Introductionmentioning

confidence: 99%

In vivo optical pathology of paclitaxel efficacy on the peritoneal metastatic xenograft model of gastric cancer using two-photon laser scanning microscopy

et al. 2014

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Background We previously visualized in vivo responses to chemotherapy in a colorectal liver metastatic xenograft model using in vivo real-time and time-series intravital two-photon laser scanning microscopy (TPLSM). In this study, we established the method for evaluating the response of peritoneal xenografts to chemotherapy of metastatic gastric cancer using intravital TPLSM. Methods Red fluorescent protein-expressing gastric cancer cells (NUGC4) were inoculated into the peritoneal cavity of green fluorescent protein nude mice. Results Laparotomy revealed that 2 weeks after inoculation, macroscopic peritoneal metastatic nodules were formed. The first intravital TPLSM session revealed that they were composed of red tumor cell clusters and green surrounding stroma. Paclitaxel was administered intraperitoneally after the first TPLSM three times a week for 7 days in the treatment group. At the second laparotomy, there were significantly fewer and smaller nodules in the treated mice than in the controls. The second intravital TPLSM session showed tumor cell fragmentation, swelling, and nuclear condensation in the metastatic nodules-a response to chemotherapy. There were multinuclear tumor cells in the paclitaxel-treated living mice.Conclusions Our method may become a powerful tool for evaluating the efficacy of novel anti-gastric cancer drugs in a preclinical murine model with minimum interindividual variation.

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Phase II study of weekly intravenous and intraperitoneal paclitaxel combined with S-1 for advanced gastric cancer with peritoneal metastasis

Abstract: Combination chemotherapy of i.v. and i.p. PTX with S-1 is well tolerated and active in gastric cancer patients with peritoneal metastasis.

Cited by 210 publications

References 26 publications

Feasibility of weekly intraperitoneal versus intravenous paclitaxel therapy delivered from the day of radical surgery for gastric cancer: a preliminary safety analysis of the INPACT study, a randomized controlled trial

Feasibility of weekly intraperitoneal versus intravenous paclitaxel therapy delivered from the day of radical surgery for gastric cancer: a preliminary safety analysis of the INPACT study, a randomized controlled trial

Surgery with curative intent for stage IV gastric cancer: Is it a reality of illusion?

In vivo optical pathology of paclitaxel efficacy on the peritoneal metastatic xenograft model of gastric cancer using two-photon laser scanning microscopy

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