Intraoperative intraperitoneal administration of CDDP against gastric cancer with peritoneal dissemination

This study was undertaken in order to evaluate the effect of intraoperative intraperitoneal (i.p.) administration of CDDP on patients who underwent gastrectomy for gastric cancer with peritoneal dissemination, compared with MMC or OK-432 i.p. administration group and untreated group. The median survival time was 11 months in CDDP i.p. group (35 patients), 8 months in MMC or OK-432 Ip group (33 patients) and 7 months in untreated group (25 patients). 1- and 2-year survival rates were 30.4% and 12.1% for MMC or OK-432 i.p. group, and 28% and 8% for untreated group, while in CDDP i.p. group, the rates were higher at 46.4% and 14.7%, respectively (CDDP i.p. group vs. untreated group, p less than 0.05). In vitro chemosensitivity test by succinate dehydrogenase inhibition (SDI) test supported the clinical results. CDDP had higher sensitivities than MMC and ADM on poorly differentiated cases as well as peritoneal dissemination cases. Our results suggest that intraoperative i.p. administration of CDDP was useful for the treatment of gastric cancer with peritoneal dissemination.     

Safety and efficacy of hypotonic CDDP intraperitoneal administration for gastric cancer with peritoneal dissemination

We examined safety and efficacy of hypotonic CDDP intraperitoneal administration followed by systemic chemotherapy using MTX/5-FU and UFT. Between 1998 and 2004, seven patients who had histologically proven gastric adenocarcinoma with peritoneal metastases underwent palliative gastrectomy at Niigata University Medical Hospital. For residual peritoneal tumors, 100 mg/body of CDDP diluted with distilled water was intraperitoneally administered to the patients before closure of abdominal wall and was drained 30 to 60 minutes after administration. During the postoperative period, a patient suffered from intraperitoneal abscess and another patient had a renal dysfunction with an increasing level of serum Cr (2.1 mg/dl). As adverse effects of the following systemic chemotherapy, three patients had grade 3 anemia and one had grade 3 leukopenia. The median time to progression was 109 days and the median survival time was 248 days. Although intraperitoneal CDDP administration is safe to be carried out intraoperatively, the effect on survival is not better than new anticancer drugs, such as TS-1 and paclitaxel.     

A case of advanced gastric cancer with peritoneal dissemination responding to S-1/CDDP neoadjuvant chemotherapy

The patient was a 72-year-old male diagnosed with type III poorly-differentiated adenocarcinoma in the lesser curvature by gastric fiberscopy. An abdominal computed tomography (CT) scan showed the thickness of the gastric wall and the enlarged lymph node around the stomach and laparoscopic examination revealed peritoneal dissemination. The patient received neoadjuvant combined chemotherapy with S-1 and CDDP. S-1 (100 mg/day) was orally administered for 3 weeks followed by 2 drug-free weeks as a course, and CDDP (100 mg/body) was administered by intravenous drip on day 8. After the third course, significant tumor reduction was obtained. Total gastrectomy, splenectomy and D2 nodal dissection were performed. Peritoneal dissemination disappeared, and the histological diagnosis revealed complete disappearance of cancer cells in the ascites and no metastasis in all lymph nodes. The patient has now been in good health with no recurrence for 22 months after surgery. The combined neoadjuvant chemotherapy with S-1 and CDDP can be an effective treatment of choice for advanced gastric carcinoma with peritoneal dissemination.     

A case of advanced gastric cancer with peritoneal dissemination successfully treated with S-1 and intraperitoneal docetaxel administration

A 76-year-old man was admitted to our hospital for the treatment of remnant gastric cancer. Laparotomy revealed massive lymph node metastasis, direct invasion of the transverse colon, and peritoneal dissemination. Partial resection of remnant stomach with transverse colon and intraperitoneal infuser port implantation were performed. After surgery, he underwent chemotherapy with docetaxel(DOC)administered intraperitoneally, and S-1. CT scan showed no tumors, and the patient was judged to be a complete response(CR)without serious adverse events. We switched DOC to intravenous injection because of port damage, and grade 3 adverse events appeared frequently until the chemotherapy was stopped. It has been 30 months since we stopped the chemotherapy, and the patient is still alive with no evidence of tumor recurrence 48 months after surgery.     

The significance of low-dose CDDP intraperitoneal administration for cases of peritoneal dissemination of gastric cancer

We examined the significance of low-dose cisplatinum (CDDP) intraperitoneal administration for cases of peritoneal dissemination of gastric cancer. Sixty-eight cases of gastric cancer, diagnosed as P1 or CY1 in the gastrectomy operation that was carried out during the period between January 1994 and December 2001, were studied based on accumulated survival rate and mean survival time (MST). Ten milligram of CDDP was weekly administrated intraperitoneally through an infusion port. A two-week interval was taken after the eight-week administration. This group, the CDDP intraperitoneal administration group, was statistically superior both in the accumulated survival rate and MST. These results suggested that the low-dose CDDP intraperitoneal administration would contribute to improved prognosis of such gastric cancers as P1 or CY1.     

A case report of advanced gastric cancer with peritoneal dissemination effectively treated by combination chemotherapy of S-1 and docetaxel

The present patient was a 69-year-old male diagnosed as gastric cancer with peritoneal dissemination by staging laparoscopy. He was treated with chemotherapy using S-1 (120 mg/body/day) and docetaxel (70 mg/body/day 1) administered for 2 weeks, followed by one drug-free week in three-week courses. After 4 courses of treatment, the primary tumor regressed, but only slightly. Because of an adverse event, we continued with a lower dose. After 4 more courses of treatment, the primary tumor and dissemination were undetectable on abdominal CT scan but were endoscopically detected. The patient has been followed on an outpatient basis without surgical treatment for 2 years.     

A case report of curative resection for gastric cancer with peritoneal dissemination successfully treated by combined chemotherapy of S-1 and paclitaxel

The patient was a 54-year-old female with gastric cancer. As laparotomy showed diffuse peritoneal dissemination, only laparotomy was performed and chemotherapy was conducted with a combination of S-1 80 mg/m(2) (2 weeks administration and 1 week rest) and paclitaxel (PTX) 50 mg/m(2) (day 1, 8). After 5 courses of this regimen, endoscopy showed the tumor was reduced in size and PET-CT revealed no evidence of metastasis. She underwent total gastrectomy with D2 lymph node dissection and Roux-en Y reconstruction. Peritoneal metastasis histologically disappeared, and the final findings were T1, N0, H0, P0, CY0, M0, Stage I A, Cur A. The only adverse effect was grade 1 stomatitis during this chemotherapy. CT showed no findings of recurrence 11 months after the operation. The S-1/PTX combination chemotherapy was thought to be effective for gastric cancer with peritoneal dissemination and made curative operation possible in this case.     

Repeated intraperitoneal chemotherapy for peritoneal dissemination from gastric carcinoma

Repeated intraperitoneal chemotherapy (RIC) via i.p. port was carried out in 16 patients with peritoneal dissemination P(+) and 8 with positive washing cytology P0.cy (+). CDDP with/without MMC soluted by physiological saline was periodically administered via i.p. port. The average administration was 5.6 times (2-16, median: 6) and the average dose was 288.0 mg. As the results, negative change of washing cytology after RIC was found in 71%, with a high rate especially in P0.cy (+) cases. Also, median survival time (MST) of responders was statistically longer than that of non-responders (777 days vs 254 days). Although diarrhea and anorexia of grade 3 developed once in each one patient, serious toxicities were not found. In conclusion, RIC is effective for peritoneal dissemination, especially P0.cy (+) cases, from gastric carcinoma.     

Repeated intraperitoneal chemotherapy for peritoneal dissemination from gastric carcinoma

Repeated intraperitoneal chemotherapy (RIC) via an i.p. port system was carried out in 16 patients with peritoneal dissemination (P1) and in 10 with positive washing cytology (P0.CY1) from gastric carcinoma. CDDP dissolved in 500-1,000 ml of physiological saline solution was periodically administered via the i.p. port system. The change of washing cytology (CY), which was obtained from i.p. port, was examined before each administration as a indicator of the response. The average number of administrations was 5.7 and the average total dose was 301.7 mg. As a result, a negative change of CY after RIC was found in 74% of patients, and also more than 80% of the response occurred within three administrations. The prognosis tended to be better in P0.CY1 patients than in P1 patients. In particular, the median survival time of the CY responders markedly improved as compared with non-responders (27.8 months versus 7.1 months). Although diarrhea and anorexia of grade 3 developed once in each patient, serious toxicities were not found. In conclusion, we consider RIC to be an effective therapy for P0.CY1 among cases with peritoneal dissemination from gastric carcinoma.     

A case of gastric cancer with peritoneal dissemination successfully treated by S-1/paclitaxel combination chemotherapy

A 62-year-old woman visited our hospital with diarrhea, bloating, vomiting, and black stool. Borrmann-type 3 gastric cancer with hemorrhaging was revealed by stomach endoscopy. The biopsy showed a poorly-differentiated adenocarcinoma. Moreover, peritoneal dissemination was found by computed tomography and we combined S-1 80 mg/m2(4 weeks administration and week rest)with paclitaxel(PTX)50 mg/ m2 (day 1, 8, 15, 3 weeks rest). After 2 courses, endoscopy showed tumor shrinkage. Therefore, we conducted total gastrectomy with resection of gall bladder and spleen. The final findings were Stage II .We conducted S-1/PTX combination chemotherapy(4 courses)followed by monotherapy as adjuvant chemotherapy. Recently, the woman had been living without relapse four years after operation.     

A surgically resected case of advanced gastric carcinoma with peritoneal dissemination after treatment with combined chemotherapy of TS-1 and CDDP

A 60-year-old female had undergone laparoscopic oophorectomy for right ovarian tumor. At the time of surgery, peritoneal dissemination and ascites was observed. Histological examination revealed that the resected ovary, peritoneal nodes and floating cells in the ascites were metastatic adenocarcinomas. Later, the primary malignant lesion was found to be a type 4 gastric carcinoma. The carcinoma was judged to be unresectable and treated by combination chemotherapy with TS-1 and CDDP every 6 weeks. After 3 courses of treatments, upper gastrointestinal series and endoscopic examinations were conducted and revealed a marked reduction of the tumor size. No carcinoma cells were detected by endoscopic biopsy. CT-scan showed complete disappearance of metastatic lesions. Staging laparoscopy was performed for evaluation of the effects of chemotherapy, and no adenocarcinoma cells at peritoneal nodes or ascites were found histologically. We performed total-gasterectomy with D1 + alpha lymph node dissection. Histopathologically, resected specimens showed severe fibrosis in most parts of the stomach. Following chemotherapy, the carcinoma was judged to be Grade 2 by histopathological examination.     

A case report of the combination therapy with S-1 plus CDDP intraperitoneal chemotherapy for CY positive cancer patient

A male patient in his 50s underwent distal gastrectomy for gastric cancer. In operation, there was no peritoneal dissemination. But peritoneal lavage cytology revealed positive peritoneal dissemination. Thus, we set an intraperitoneal infuser port to this patient. On specimen, a type-3 tumor was located in the gastric lesser of antrum to angle. Microscopic examination of specimens revealed a signet ring cell carcinoma and poorly differentiated adenocarcinoma under serosa, and positive of lymph node metastasis. The diagnosis was pT4N2M1P0CY1H0, Stage IV( Japanese classification of gastric carcinoma The 14 Edition). CDDP was administered through the infuser port (on day 7, a first dose of 60 mg/m2 and 30 mg/m2 for second) combined with oral administration of S-1 (100 mg/body) for two weeks, with one week of drug withdrawal. This chemotherapy was repeated for 11 courses. After that, peritoneal lavage cytology became negative. S-1 oral administration was continued for four years, and this patient has been well for five years and six months after the surgery. Therefore, it is suggested that intraperitoneal chemotherapy with cisplatin is an effective treatment for microscopical peritoneal dissemination.     

A case of advanced gastric cancer with peritoneal dissemination responding remarkably to TS-1/CDDP combination chemotherapy

A 57-year-old woman visited a physician with complaints of anorexia and pollakiuria. Because a pelvic tumor and ascites were detected, she was referred to our department. Douglas pouch puncture revealed adenocarcinoma cells. Further examination showed an advanced gastric cancer with peritoneal dissemination. The cancer was judged to be unresectable. Chemotherapy with a combination of TS-1 and CDDP was performed before the operation. After 2 courses of the chemotherapy, her complaints disappeared, although abdominal CT confirmed remaining peritoneal dissemination. After 7 courses of chemotherapy, abdominal CT showed that the peritoneal dissemination had disappeared. Total gastrectomy and lymph node dissection were performed. Histological findings of the stomach revealed complete disappearance of cancer cells in the stomach and the regional lymph nodes. We confirmed that the TS-1/CDDP therapy resulted in a complete response to advanced gastric cancer and peritoneal dissemination. We recommend that chemotherapy be continued until the peritoneal dissemination disappears.     

Studies of the effectiveness and optimal administration of repeated intraperitoneal chemotherapy for peritoneal dissemination from gastric cancer

The optimal interval for drug administration was examined for repeated intraperitoneal chemotherapy (IPC). The subjects were 31 patients who underwent curative surgical resection excluding P1 or CY1 factor, followed by IPC. IPC was carried out 180 times in total, and the intervals were divided into three groups: 2-week interval 45 times, 3-week interval 10 times and 4-week or greater interval 94 times. The optimal method of drug administration was evaluated from the therapeutic outcome and the development of adverse effects with each interval time. The cytology of ascites obtained via an i.p. port was examined before each drug administration, and those with a negative change (CY0) were judged as responders. The adverse effects in the patients receiving drugs at 2-week intervals were grade 1 or 2, although the incidence was high compared with other patients. All responders obtained a negative change in CY within six courses. At present, we conclude that it is reasonable for IPC to be carried out six times at 2-week intervals.     

Neoadjuvant chemotherapy with S-1 and surgical resection for a mucinous gastric cancer with peritoneal dissemination

We herein report the case of a patient with mucinous gastric carcinoma with peritoneal dissemination that disappeared after neoadjuvant chemotherapy with S-1 alone. The patient has survived for over 23 months after surgery, without recurrence. A 60-year old man was referred to our hospital because of an advanced gastric cancer, detected by upper gastrointestinal endoscopy at another hospital. Staging laparoscopy was performed on October 25, 2002, and revealed massive peritoneal dissemination. Two courses of neoadjuvant chemotherapy with S-1 were administered, at 120mg/day for 28 days, as one course. Total gastrectomy, with D2 lymph node dissection, was performed on January 24, 2003. The peritoneal dissemination had macroscopically disappeared and the cytology of the peritoneal lavage fluid was class III. His final diagnosis was gastric carcinoma, MLU, type 3, T2(SS), P0, H0, M0, N3, CY0, stage IV.     

Preoperative combination chemotherapy with TS-1 is effective in a case gastric cancer with peritoneal dissemination

We report a case of peritoneal cancer dissemination with Type 4 gastric cancer, successfully treated with combination chemotherapy with TS-1. The patient was a 59-year-old female, who complained of abdominal distension with pain, weight loss, and poor appetite. She was diagnosed as unresectable Type 4 gastric cancer, T3N2MOHOP1CY1M0, Stage IV with massive ascites (cytology: Class V). After 2 courses of combined chemotherapy with TS-1 and cisplatin (CDDP), primary tumor reduction was confirmed and no cancer cells were detected from a pathological investigation with biopsied specimens by endoscopy. As additional therapy for remained ascites, intraperitoneal administration of paclitaxel and docetaxel was performed, resulting in a remarkable decrease of ascites with cytological disappearance of cancer cells. The patients underwent total gastrectomy with lymph node dissection, pathological diagnosis of primary site and lymph nodes showed grade 2 effect, and no cancer cells were detected in ascites and peritoneum, microscopically. While she died of peritoneal recurrence after the surgery, the case suggested the clinical advantage of controlling the advanced cancer-bearing state by combination chemotherapy with TS-1, instead of surgery.     

Repeated intra-abdominal administration of CDDP in carcinomatous peritonitis due to gastric cancer--a case report

Two years and 10 months after gastrectomy, a 38-year-old man was diagnosed as having carcinomatous peritonitis due to gastric cancer. He was treated by intra-abdominal administration of 100 mg CDDP three times in addition to UFT. After each administration of CDDP, the amount of ascites and the serum value of CEA were decreased. Subjective symptoms, such as epigastric pain or sensation of fullness, were also improved. Although one year and 8 months has passed since the first administration of CDDP, the performance status of the patient remains 0. Nausea or vomiting was noted within 2 days after each administration. However, severe complications, like renal failure or intra-abdominal hemorrhage, were not observed. These findings suggest that repeated intra-abdominal administration of CDDP may be a useful therapy for carcinomatous peritonitis due to gastric cancer.     

A case of advanced gastric cancer with peritoneal dissemination effectively treated with fourth-line chemotherapy of S-1 alone

The patient was a 42-year-old female diagnosed with unresectable highly advanced gastric cancer complicated by peritoneal dissemination. We performed systemic chemotherapy with MTX+5-FU as the first-line treatment, which stabilized the disease. Since the patient initially wished a radical resection, we tried chemotherapy with weekly PTX as a second-line treatment. Her therapeutic response remained between a partial response and a stable disease for about five months, followed, however, by progressive disease. The result of the third-line treatment with CPT-11+CDDP was again a progressive disease, so we switched her regimen to single-agent S-1 as a fourth-line treatment. The ascites disappeared three months after the change in regimen. As of March 2006, the patient had survived for 17 months since diagnosis (8 months since the ongoing S-1 therapy started) and the disease is currently stabilized, and preserving a favorable performance status. However, in June 2006, the patient died of pneumonia 20 months after the diagnosis.