Pharmacokinetics of intraperitoneal docetaxel and S-1 in patients with gastric cancer with peritoneal carcinomatosis

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e15672-e15672
Author(s):  
K. Hayashi ◽  
H. Kamikozuru

e15672 Background: One of the most causes of death from gastric cancer is peritoneal cartinomatosis. Intraperitoneal docetaxel infusion is expected to be a new strategy for a treatment of peritoneal carcinomatosis. The purpose of this study is to evaluate the plasma and peritoneal pharmacokinetic of intraperitoneal docetaxel infusion in combination with oral administration of S-1. Methods: Eight patients with peritoneal carcinomatosis of advanced gastric cancer were enrolled. Docetaxel was dissolved in an isotonic saline to a final 1 liter solution and administered in 2 hour via an implanted intraperitoneal catheter at dosage of 40mg/m2. Five of eight patients were administered S-1 orally at dosage of 80mg/m2. Blood and peritoneal fluid were collected before administration, on completion of the docetaxel infusion(hour 0) and at hours 1,2,4,6,12,24,48,and 72 after completion of the infusion of the docetaxel. Plasma and peritoneal fluid concentrations of docetaxel and 5FU were evaluated. Results: The mean peak peritoneal and plasma concentrations of docetaxel were 18.6×103 ng/ml (at hour 0) and 45 ng/ml (at hour 0 to 2), respectively. The peritoneal concentrations of docetaxel were remained even after 24 and 72 hours (24 hours: 1150ng/ml, 72 hours: 74ng/ml). In seven out of eight patients, plasma concentrations of docetaxel were disappeared after 24 hours, but in only one patient with severe ascites, concentration of plasma docetaxel at hour 24 could be obtained (20 ng/ml). The mean peritoneal and plasma areas under the curves (AUC) of doceta×el were 141x103 ng/ml×hr and 480 ng/ml×hr, respectively. The mean peritoneal concentrations of 5FU kept over 60% of plasma concentrations (plasma: 164.3ng/ml, peritoneal: 105ng/ml). Conclusions: Intaperitoneal docetaxel kept relatively high concentrations even after 72hours. 5FU concentrations were well transfered in peritoneal fluid from plasma via oral S-1 administration. Intraperitoneal docetaxel in combination with S-1 orally may be a useful regimen to the patients with carcinomatosis of advanced gastric cancer. No significant financial relationships to disclose.

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e15626-e15626
Author(s):  
H. Kamikozuru ◽  
K. Hayashi ◽  
H. Kuramochi ◽  
G. Nakajima ◽  
M. Yamamoto

e15626 Background: One of the most causes of death from gastric cancer is peritoneal cartinomatosis. Intraperitoneal docetaxel infusion is expected to be a new strategy for a treatment of peritoneal carcinomatosis. The purpose of this study is to evaluate the plasma and peritoneal pharmacokinetic of intraperitoneal docetaxel infusion in combination with oral administration of S-1. Methods: Eight patients with peritoneal carcinomatosis of advanced gastric cancer were enrolled. Docetaxel was dissolved in an isotonic saline to a final 1 liter solution and administered in 2 hour via an implanted intraperitoneal catheter at dosage of 40mg/m2. Five of eight patients were administered S-1 orally at dosage of 80mg/m2. Blood and peritoneal fluid were collected before administration, on completion of the docetaxel infusion(hour 0) and at hours 1,2,4,6,12,24,48,and 72 after completion of the infusion of the docetaxel. Plasma and peritoneal fluid concentrations of docetaxel and 5FU were evaluated. Results: The mean peak peritoneal and plasma concentrations of docetaxel were 18.6×103 ng/ml (at hour 0) and 45 ng/ml (at hour 0 to 2), respectively. The peritoneal concentrations of docetaxel were remained even after 24 and 72 hours (24 hours: 1150ng/ml, 72 hours: 74ng/ml). In seven out of eight patients, plasma concentrations of docetaxel were disappeared after 24 hours, but in only one patient with severe ascites, concentration of plasma docetaxel at hour 24 could be obtained (20 ng/ml). The mean peritoneal and plasma areas under the curves (AUC) of docetaxel were 141×103 ng/ml×hr and 480 ng/ml×hr, respectively. The mean peritoneal concentrations of 5FU kept over 60% of plasma concentrations (plasma: 164.3ng/ml, peritoneal: 105ng/ml). Conclusions: Intaperitoneal docetaxel kept relatively high concentrations even after 72hours. 5FU concentrations were well transfered in peritoneal fluid from plasma via oral S-1 administration. Intraperitoneal docetaxel in combination with S-1 orally may be a useful regimen to the patients with carcinomatosis of advanced gastric cancer. No significant financial relationships to disclose.


Reproduction ◽  
2000 ◽  
pp. 49-57 ◽  
Author(s):  
SD Johnston ◽  
MR McGowan ◽  
P O'Callaghan ◽  
R Cox ◽  
V Nicolson

As an integral part of the development of an artificial insemination programme in the captive koala, female reproductive physiology and behaviour were studied. The oestrous cycle in non-mated and mated koalas was characterized by means of behavioural oestrus, morphology of external genitalia and changes in the peripheral plasma concentrations of oestradiol and progestogen. The mean (+/- SEM) duration of the non-mated oestrous cycle and duration of oestrus in 12 koalas was 32.9 +/- 1.1 (n = 22) and 10.3 +/- 0.9 (n = 24) days, respectively. Although the commencement of oestrous behaviour was associated with increasing or high concentrations of oestradiol, there were no consistent changes in the morphology or appearance of the clitoris, pericloacal region, pouch or mammary teats that could be used to characterize the non-mated cycle. As progestogen concentrations remained at basal values throughout the interoestrous period, non-mated cycles were considered non-luteal and presumed anovulatory. After mating of the 12 koalas, six females gave birth with a mean (+/- SEM) gestation of 34.8 +/- 0.3 days, whereas the remaining six non-parturient females returned to oestrus 49.5 +/- 1. 0 days later. After mating, oestrous behaviour ceased and the progestogen profile showed a significant increase in both pregnant and non-parturient females, indicating that a luteal phase had been induced by the physical act of mating. Progestogen concentrations throughout the luteal phase of the pregnant females were significantly higher than those of non-parturient females. Parturition was associated with a decreasing concentration of progestogen, which was increased above that of basal concentrations until 7 days post partum.


PLoS ONE ◽  
2018 ◽  
Vol 13 (3) ◽  
pp. e0194755 ◽  
Author(s):  
Hae Young Kim ◽  
Young Hoon Kim ◽  
Gabin Yun ◽  
Won Chang ◽  
Yoon Jin Lee ◽  
...  

2015 ◽  
Vol 33 (3_suppl) ◽  
pp. 215-215
Author(s):  
Sang Woo Lee ◽  
In Keun Choi ◽  
Chang Min Lee ◽  
Seung Young Kim ◽  
Jong Jin Hyun ◽  
...  

215 Background: The purpose of this study is to evaluate significant prognostic factor and compare the cause of death in patients with advanced or recurrent gastric cancer. Methods: We reviewed the medical records of 170 patients who had been diagnosed as advanced or recurrent gastric cancer between January 2006 and September 2013. The patients were divided into two groups. One group (advanced gastric cancer: AC) included 104 patients had undergone chemotherapy for advanced gastric cancer, and the other group (recurrent gastric cancer: RC) 66 for recurrence after surgical treatment. The causes of death and overall survival were compared between two groups, and the significant prognostic factors were investigated by multivariate analysis. Also, subgroup analysis was performed for 18 patients with gastrectomy for curative intent, and they were proved to have unresectable gastric cancer after surgery (non-palliative surgery for advanced gastric cancer: NS). Results: In the comparison for the causes of death, two groups showed no statistical difference, but AC group had more tendency to die because of bleeding ( p = 0.054) and infection ( p = 0.075). Overall survival of AC group did not differ from that of RC ( p = 0.901). In multivariate analysis, bone metastasis ( p = 0.013, HR = 1.923), peritoneal seeding ( p = 0.001, HR = 2.182) and the frequency of chemotherapy ( p < 0.001, HR = 0.887) were significantly associated with the overall survival. In a subgroup analysis, the overall survival of NS was significantly higher than AC ( p = 0.032). Conclusions: In the patients with advanced or recurrent gastric cancer, AC might have more possibility to die because of bleeding and infection than RC. Additionally, the prognosis of patients with advanced or recurrent gastric cancer was affected by the presence of bone metastasis, peritoneal seeding and frequency of chemotherapy. Non-palliative surgery for gastric cancer might show the better prognosis than AC in the specific conditions.


2015 ◽  
Vol 33 (3_suppl) ◽  
pp. 159-159
Author(s):  
Ziyu Li ◽  
Sheng Ao ◽  
Jiafu Ji

159 Background: There were no ideal materials nor quantizing regime for surgeons’ training on harvesting lymph nodes in advanced gastric cancer(AGC). A prospective randomized trial on Carbon Nanoparticles (CNP),a kind of lymphatic tracers, was designed to find a solution. Methods: Patients with previously untreated resectable AGC were eligible for inclusion in this study. All patients were randomly allocated to two subgroups. In experimental group, total of 1.0 mL CNP was injected into the subserosa of stomach around the tumor before gastrectomy with D2 dissection performed. On the contrary, the same procedure was performed directly without any coloring materials in control arm. Following surgery,the investigator harvested lymph nodes (LNs), counted colored LNs and measured the diameters with pathologist. Results: 30 patients were enrolled in the study. We observed no serious adverse effects related to CNP injection. The rate of stained LNs was 46.6%. The mean number of harvested LNs was larger in experimental than control group (38.33 vs. 28.27, p=0.041). Smaller diameter was recorded in experimental arm (3.32vs4.30mm,p=0.023), which might clarify the reason why the number of LNs was larger with CNP. In addition, we set up a model for predicting total number of LNs based on the data of CNP-staining LNs and metastatic LNs(MLNs), which might help the surgeons review their work of removing LNs so as to improve their surgical skills. Conclusions: CNP was a kind of safe materials and surgeons could harvest more LNs with it in AGC, which might benefit from the harvest of more smaller ones. Further study was needed to prove the model’s practicability. Clinical trial information: NCT02123407.


2017 ◽  
Vol 35 (4_suppl) ◽  
pp. 43-43
Author(s):  
Daxing Xie ◽  
Jianping Gong

43 Background: D2 lymphadenectomy has been widely accepted as a standard procedure of surgical treatment for local advanced gastric cancer [1,2]. However, neither the dissection boundary nor the extent of the excision for perigastric soft tissues has been described [3-7]. Our previous researches demonstrate the existence of disseminated cancer cells in the mesogastrium [8, 9] and present an understandable mesogastrium model for gastrectomy [10]. Hence, the D2 lymphadenectomy plus complete mesogastrium excision (D2+CME) is firstly proposed in this study, aiming to assess the safety, feasibility and corresponding short-term surgical outcomes. Methods: All of these patients underwent laparoscopy assisted D2+CME radical gastrectomy with a curative R0 resection, and all the operation was performed by Prof. Jianping Gong, chief of GI surgery of Tongji Hospital, Huazhong University of Science and Technology. All participants provided informed written consent to participate in the study. This study was approved by the Tongji Hospital Ethics Committee. The standard surgical procedures in the video are described as follows. Reconstruction of the alimentary tract was done by extracorporeal anastomosis. Standard recovery protocols were followed in postoperative treatments. Results: 68 patients between September 2014 and March 2016 have been recruited with informed consent and underwent laparoscopic D2+CME by a single surgeon. The mean number of retrieved regional lymph nodes was 33.62±11.40 (ranges 14-55). The mean volume of blood loss was 12.44±22.89 ml (ranges 5-100). The mean laparoscopic surgery time was 127.82±17.63 mins (ranges 110-165). The mean hospitalization time was 16.5±3.3 days (ranges 8-28). No operative complication was observed during the hospitalization. Conclusions: The anatomical boundary of mesogastrium is well described and dissected within D2+CME surgical process. It proves to be safely feasible and repeatable with less blood lost, qualified lymph nodes, retrieval results, and other improved short-term surgical outcomes in advanced gastric cancer. Meanwhile, potential disseminated cancer cells fall into the mesogastrium can be eradicated by D2+CME. Clinical trial information: NCT01978444.


2018 ◽  
Vol 11 (2) ◽  
pp. 305-310 ◽  
Author(s):  
Renata D’Alpino Peixoto ◽  
Tercia Tarciane de Sousa ◽  
Pedro Alexandre Ismael Amaral Silva ◽  
Luciana Rodrigues de Meirelles ◽  
Carlos Henrique Andrade Teixeira

Background: Peritoneal carcinomatosis is usually a terminal disease with short median survival in patients with gastric cancer. Systemic FOLFOX is one of the most used regimens in the first-line treatment of metastatic gastric cancer. However, there is scarce evidence that cytoreductive surgery (CRS) and intraperitoneal heated chemotherapy (HIPEC) improves oncological outcomes of patients with advanced gastric cancer. Methods: Herein we present a case of a young woman with advanced gastric cancer with omental and peritoneal metastases who achieved an excellent response after 6 months of FOLFOX followed by CRS and HIPEC. Results: A 53-year-old woman was diagnosed with advanced gastric carcinoma, with extensive omental caking and several peritoneal implants measuring 2 cm at the largest diameter. The patient received mFOLFOX6 for 6 months with excellent clinical and radiographic response. She was then submitted to a D2 total gastrectomy followed by CRS and HIPEC with mitomycin. The final pathology report showed a focal adenocarcinoma in the stomach measuring 0.4 mm with no residual tumor in the peritoneum (ypT1ypN0). The patient has been well and disease free for more than 4 years. Conclusion: While still controversial, CRS followed by HIPEC may be a curative therapeutic option for highly selected patients.


2013 ◽  
Vol 39 (9) ◽  
pp. S37-S38
Author(s):  
M. Benedetti ◽  
M. Valle ◽  
L. Cenci ◽  
G.B. Levi Sandri ◽  
F. Stefanelli ◽  
...  

2021 ◽  
Vol 108 (Supplement_3) ◽  
Author(s):  
M García Munar ◽  
M Merayo Álvarez ◽  
M Moreno Gijón ◽  
R Rodríguez Uría ◽  
J L Rodicio Miravalles ◽  
...  

Abstract INTRODUCTION The incidence of peritoneal metastases in gastric cancer are frequent and are associated with very poor median survival rates. The multimodal treatment of cytoreduction surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) could offer a better prognosis in selected cases although it is not currently contemplated in clinical practice guidelines. MATERIAL AND METHODS Of the 100 patients operated on for peritoneal carcinomatosis in our centre between May 2014 and December 2020, we selected those of gastric origin. Multidisciplinary CRS treatment with HIPEC was indicated in those patients with positive cytology and/or preoperative PCI &lt;7. RESULTS Four men and one woman with a mean age of 63 years underwent surgery. The mean preoperative PCI was 2 and complete cytoreduction was achieved in all cases (CC-0). Complications included a biliary leak, a postoperative collection and a bronchoaspirative pneumonia. One patient died at 34 months. The other four are still alive: one with recurrence at 18 months and the rest without disease with a mean follow-up of 25 months. In one of the cases CRS surgery with HIPEC was performed as surgical salvage after initial surgery and in the rest as the only treatment. CONCLUSIONS Palliative systemic chemotherapy is considered the treatment of gastric cancer with peritoneal involvement, however, treatment based on CRS and HIPEC in selected cases could improve survival rates, disease-free interval and even be considered as salvage treatment in resectable oligometastatic recurrences.


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