s-1-(combination) and Ascites

Objectives The aim of this study was to evaluate the safety and efficacy of intravenous and intraperitoneal paclitaxel (PTX) combined with S-1 for treatment of gemcitabine-refractory pancreatic cancer with malignant ascites. Methods After the feasibility of this regimen was first confirmed in an interim analysis in 10 patients, a total of 35 patients were enrolled between April 2011 and December 2014. PTX was administered intravenously (50 mg/m(2)) and intraperitoneally (20 mg/m(2)) on days 1 and 8, and 80 mg/m(2) S-1 was administered on days 1-14 every 3 weeks. The primary endpoint was overall survival (OS). The secondary endpoints were progression-free survival (PFS), the objective tumor response, efficacy against malignant ascites, and safety. Result In all 35 patients, the median OS and PFS were 4.8 (95 % confidence interval [CI], 2.1-5.3) months and 2.8 (95 % CI, 0.9-4.1) months, respectively. The 26 patients who were evaluable for efficacy achieved a response rate of 8 % and a disease control rate of 69 %. Malignant ascites had disappeared or decreased in 18 (69 %) patients, including complete resolution in 4 (15 %), and a negative change in cytological status was achieved in 8 (31 %) patients. The major grade 3/4 adverse events included neutropenia (34 %), anemia (31 %), nausea (9 %), and catheter-related infections (6 %). Conclusion Combination chemotherapy consisting of intravenous and intraperitoneal PTX with S-1 showed acceptable toxicity and favorable efficacy in pancreatic cancer patients with malignant ascites. (. UMIN000005306).

Topics: Adenocarcinoma; Administration, Intravenous; Adult; Aged; Antimetabolites, Antineoplastic; Antineoplastic Agents, Phytogenic; Antineoplastic Combined Chemotherapy Protocols; Ascites; Deoxycytidine; Disease-Free Survival; Drug Combinations; Drug Resistance, Neoplasm; Female; Gemcitabine; Humans; Infusions, Parenteral; Kaplan-Meier Estimate; Male; Middle Aged; Oxonic Acid; Paclitaxel; Pancreatic Neoplasms; Tegafur; Treatment Outcome

Here, we reported an interim analysis of feasibility and safety in the first 10 cases of 30 cases in a phase II trial of intravenous and intraperitoneal paclitaxel combined with S-1 for gemcitabine-refractory pancreatic cancer with malignant ascites.. Paclitaxel was administered intravenously at 50 mg/m2 and intraperitoneally at 20 mg/m2 on days 1 and 8 every 3 weeks, and S-1 was administered at 80 mg/m2/day for 14 consecutive days, followed by 7-day rest.. Between April 2011 and February 2012, ten patients were enrolled. A partial response was achieved in two patients (20%) and a disease control rate of 50%. The median time to progression and overall survival were 2.1 and 3.4 months, respectively. Malignant ascites was completely resolved in two patients (20%). Major grade 3/4 adverse events were myelosuppression including neutropenia (50%) and catheter-related infection (10%).. This novel combination chemotherapy was feasible and showed promising results in pancreatic cancer patients with malignant ascites (clinical trial registration number: UMIN000005306).

Topics: Adenocarcinoma; Aged; Alopecia; Antimetabolites, Antineoplastic; Antineoplastic Combined Chemotherapy Protocols; Ascites; Catheter-Related Infections; Deoxycytidine; Drug Administration Schedule; Drug Combinations; Drug Resistance, Neoplasm; Fatigue; Feasibility Studies; Female; Gastrointestinal Diseases; Gemcitabine; Hematologic Diseases; Humans; Infusions, Intravenous; Infusions, Parenteral; Male; Middle Aged; Oxonic Acid; Paclitaxel; Pancreatic Neoplasms; Prospective Studies; Salvage Therapy; Tegafur; Treatment Outcome

There is no standard first-line chemotherapy for advanced gastric cancer with severe peritoneal metastasis. Although fluoropyrimidine is often used, its efficacy is limited, and it remains unclear whether combination therapy with platinum improves clinical outcomes.. This retrospective study involved patients at six Japanese academic hospitals between 2010 and 2016. Patients with advanced gastric cancer and severe peritoneal metastasis were included if they had massive ascites and/or inadequate oral intake requiring intravenous nutritional support. We then compared the efficacy and safety of fluoropyrimidine monotherapy with those of fluoropyrimidine/platinum combination therapy.. Compared with the combination therapy group (n = 64), the monotherapy group (n = 65) had worse general health (more patients with elderly age, performance status > 2, and having both massive ascites and inadequate oral intake). Both overall survival (9.0 vs 5.0 months, p < 0.01) and progression-free survival (4.3 vs 2.3 months, p < 0.01) were significantly longer in the combination group, and the significance remained after adjusting for prognostic variables (hazard ratios of 0.47 and 0.41, respectively; p < 0.01). Improvements in ascites and oral intake were also greater in the combination group. Although neutropenia (grade ≥ 3) occurred more frequently with combination therapy, both treatments in this study were tolerable.. Combination therapy with fluoropyrimidine and platinum might be more effective than monotherapy with fluoropyrimidine and was tolerable for patients with advanced gastric cancer and severe peritoneal metastasis.

Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Ascites; Cisplatin; Drug Combinations; Female; Fluorouracil; Humans; Leucovorin; Male; Malnutrition; Methotrexate; Middle Aged; Neutropenia; Organoplatinum Compounds; Oxonic Acid; Peritoneal Neoplasms; Progression-Free Survival; Pyridines; Retrospective Studies; Stomach Neoplasms; Tegafur; Treatment Outcome; Withholding Treatment; Young Adult

We compared the clinical outcomes of pancreatic ductal adenocarcinoma (PDAC) resection after neoadjuvant chemoradiation therapy (NACRT) vs. chemotherapy (NAC).. The study population comprised 81 patients with UICC stage T3/4 PDAC, treated initially by NACRT with S-1 in 40 and by NAC with gemcitabine + S-1 in 41. This was followed by pancreatectomy with routine nerve plexus resection in 35 of the patients who had received NACRT and 32 of those who had received NAC. We compared the survival curves and clinical outcomes of these two groups.. The rates of clinical response, surgical resectability, and margin-negative resection were similar. The NACRT group patients had significantly higher rates of Evans stage ≥IIB tumors (29 vs. 0 %, respectively, p = 0.010) and negative lymph nodes (49 vs. 16 %, respectively, p = 0.021) than the NAC group patients. There was no difference in disease-free survival between the groups, but the disease-specific survival of the NAC group patients was better than that of the NACRT group patients (p = 0.034). Patients undergoing pancreatectomy with nerve plexus resection following NACRT had significantly higher rates of intractable diarrhea and ascites but consequently received significantly less adjuvant chemotherapy and therapeutic chemotherapy for relapse.. NACRT followed by pancreatectomy with nerve plexus resection is superior for achieving local control, but postoperative diarrhea and ascites may prohibit continuation of adjuvant chemotherapy or chemotherapy for relapse (UMIN4148).

Topics: Adult; Aged; Ascites; Carcinoma, Pancreatic Ductal; Chemoradiotherapy, Adjuvant; Chemotherapy, Adjuvant; Combined Modality Therapy; Deoxycytidine; Diarrhea; Drug Combinations; Female; Gemcitabine; Humans; Male; Middle Aged; Neoadjuvant Therapy; Oxonic Acid; Pancreatectomy; Pancreatic Neoplasms; Postoperative Complications; Tegafur; Treatment Outcome

The aim of this study was to investigate the clinical factors for predicting overall survival (OS) and the significance of a minute amount of ascites on computed tomography (CT) in patients with locally advanced pancreatic cancer (LAPC) treated with chemoradiotherapy (CRT).. Between 2003 and 2011, 48 consecutive patients with LAPC were treated with CRT. Various clinical factors, including ascites, were evaluated for correlation with OS. A subset analysis of 16 patients with a minute amount of ascites was also performed.. The median survival duration and the 1-year OS rates were 11.5 months and 50%, respectively. A minute amount of ascites on CT and elevated carbohydrate antigen 19-9 (CA19-9) level were significantly associated with poorer OS. In 16 patients with ascites, the amount of ascites increased in the course of the disease, and these were considered to be cancerous clinically, regardless of the amount.. A minute amount of ascites and CA19-9 were important prognostic factors in CRT. Any amount of ascites was considered an early indicator of peritoneal carcinomatosis in LAPC.

Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Ascites; CA-19-9 Antigen; Chemoradiotherapy; Cisplatin; Deoxycytidine; Drug Combinations; Etoposide; Female; Gemcitabine; Humans; Kaplan-Meier Estimate; Male; Middle Aged; Oxonic Acid; Pancreatic Neoplasms; Prognosis; Tegafur; Tomography, X-Ray Computed

Fifteen years after receiving a distal gastrectomy for advanced gastric cancer, a 70-year-old woman was admitted to our hospital because of abdominal fullness due to ascites. Although cytological examination showed adenocarcinoma cells in the fluid, no examination revealed the primary lesion. Peritoneal metastasis was detected via immunohistochemistry using the cell block technique. After chemotherapy failure (S-1 plus CDDP, weekly PTX, and S-1 plus DOC), the patient received S-1 and weekly intravenous and intraperitoneal injections of PTX. The ascites decreased, and she has been doing well. Our experience with this case suggests that S-1 and weekly intravenous and intraperitoneal injections of PTX is a promising means of treating gastric cancer with peritoneal metastasis.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Ascites; Drug Combinations; Female; Gastrectomy; Humans; Infusions, Intravenous; Injections, Intraperitoneal; Oxonic Acid; Paclitaxel; Peritoneal Neoplasms; Recurrence; Stomach Neoplasms; Tegafur; Time Factors

Massive malignant ascites originating from peritoneal metastasis of gastric cancer is difficult to control and resistant to chemotherapy. Cell-free and Concentrated Ascites Reinfusion Therapy (CART) is one of the types of apheresis therapy, by which filtered and concentrated ascites containing albumin and globulin is reinfused intravenously to patients. We retrospectively studied the feasibility of intraperitoneal (IP) chemotherapy combined with CART in gastric cancer patients with massive malignant ascites.. Paclitaxel (PTX) was administered via an IP access port implanted in the subcutaneous space. If patient had massive ascites at the start of treatment, paracentesis was performed through a percutaneous IP catheter and then CART was performed. PTX was administered through the catheter until the ascites diminished.. A total of 127 CART procedures in 30 patients were analyzed. The average volume of processed ascites was 3.1 L, which was concentrated to 0.33 L containing 85.5 g protein on average. Significant increases in urine volume, serum total protein and albumin level were found after the CART. Increase in body temperature (0.3°C), decrease in platelet count (3.8 × 10(4)/μl), and changes in blood pressure (2 mm Hg) were found after the CART procedure, but no clinically significant adverse event was experienced. The median survival time and 1-year survival of 30 patients who received IP chemotherapy combined with the CART procedure was 10.2 months and 43.3% respectively.. IP chemotherapy combined with CART might be a promising strategy for patients with massive malignant ascites originating from peritoneal metastasis of gastric cancer.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Ascites; Ascitic Fluid; Blood Proteins; Body Temperature; Cell-Free System; Drug Combinations; Female; Follow-Up Studies; Humans; Infusions, Intravenous; Infusions, Parenteral; Kaplan-Meier Estimate; Laparoscopy; Male; Middle Aged; Oxonic Acid; Paclitaxel; Peritoneal Neoplasms; Platelet Count; Retrospective Studies; Second-Look Surgery; Serum Albumin; Stomach Neoplasms; Tegafur; Tomography, X-Ray Computed; Treatment Outcome

Peritoneal metastasis of gastric cancer has extremely poor clinical outcomes. Recently, we developed a combination chemotherapy that used intraperitoneal (IP) paclitaxel (PTX) and produced excellent antitumor effects against peritoneal lesions. However, no information is available about the benefit of gastrectomy in cases with malignant ascites.. A total of 64 patients with severe peritoneal metastasis and ascites received IP PTX at 20 mg/m(2) via implanted subcutaneous peritoneal access ports as well as intravenous (IV) PTX at 50 mg/m(2) on days 1 and 8. S-1 was administered at 80 mg/m(2) day for 14 consecutive days, followed by 7 days of rest. In all patients, investigative laparoscopy was performed around the combination chemotherapy, and gastrectomy was performed on patients who showed apparent shrinkage of their peritoneal nodules as well as negative peritoneal cytology at the second laparoscopy.. Gastrectomy was performed in 34 patients. The median course of chemotherapy before surgery was 5 courses (range 2-16). R0 operation was achieved in 22 patients (65%), and grade 2 and 3 histological responses were obtained in 7 (21%) and 1 (3%) patient(s), respectively. The median survival time and 1-year overall survival of the gastrectomized patients were 26.4 months and 82%, and those of the 30 patients who did not receive gastrectomy were 12.1 months and 26%, respectively. Morbidity was minimal, and there was no mortality.. Salvage gastrectomy after chemotherapy of S-1 with IV and IP PTX is promising, even for patients with highly advanced gastric cancer and severe peritoneal metastasis and malignant ascites.

Topics: Administration, Oral; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Ascites; Combined Modality Therapy; Drug Combinations; Female; Follow-Up Studies; Humans; Injections, Intraperitoneal; Lymphatic Metastasis; Male; Middle Aged; Neoplasm Staging; Ovarian Neoplasms; Oxonic Acid; Paclitaxel; Peritoneal Neoplasms; Prognosis; Salvage Therapy; Stomach Neoplasms; Survival Rate; Tegafur

There are few data on the efficacy of combination chemotherapy with a fluoropyrimidine plus cisplatin for patients with advanced or recurrent gastric cancer (AGC) complicated by peritoneal metastasis, especially massive ascites.. We retrospectively evaluated the efficacy and safety of a fluoropyrimidine (S-1 or capecitabine) plus cisplatin as first-line chemotherapy in 120 patients with AGC and peritoneal metastasis.. Ascites was detected in 50 patients, with 11 patients having massive ascites. Median progression-free survival (PFS) and overall survival (OS) of all patients was 6.1 and 15.9 months, respectively. The PFS and OS were shorter in patients with massive ascites (n = 11; 3.7 and 9.5 months) compared with patients with small or moderate ascites (n = 39; 5.8 and 13.5 months) or patients without ascites (n = 70; 6.9 and 18.1 months). The objective response in terms of ascites was similar whether ascites was massive (4 of 11 patients; 36.4%) or small or moderate (16 of 39 patients; 41%). The frequencies of grade 3 or higher toxicity or treatment discontinuation due to toxicity are relatively similar across ascites groups.. Fluoropyrimidine plus cisplatin appears to be tolerated in selected patients with peritoneal metastasis.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Ascites; Capecitabine; Cisplatin; Deoxycytidine; Disease-Free Survival; Drug Combinations; Female; Fluorouracil; Humans; Male; Middle Aged; Neoplasm Recurrence, Local; Oxonic Acid; Peritoneal Neoplasms; Retrospective Studies; Stomach Neoplasms; Survival Rate; Tegafur; Time Factors; Treatment Outcome

We report two cases of advanced gastric cancer. The first was a 77-year-old man who had experienced distal gastrectomy about 35 years ago. He complained of abdominal bloating, and a gastrointestinal scope showed that he had advanced gastric cancer. CT scan revealed massive ascites. Dissemination of the peritoneum was suspected, and chemotherapy using S-1 (80mg/m², biweekly)plus paclitaxel (50mg/m², on days 1 and 8) was selected, He had no major side effects and the ascites disappeared. He was able to receive 18 courses on an outpatient basis. The second case was a 79-year-old man who had total gastrectomy performed 1 year ago. Invasion to the diaphragm and lymph node metastasis were detected. We selected S-1 (80 mg/m²)as adjuvant chemotherapy but that caused severe fatigue. Eventually he refused the drug. Six month later, he had abdominal bloating and CT scan revealed that he had massive ascites. UFT-E (1. 5 g/body) was administered and paclitaxe (l 50 mg/m²) was added. The ascites disappeared and he has had a stable life. DIF (S-1, UFT) plus paclitaxel is considered to be a useful chemotherapy combination against advanced gastric cancer that has peritoneal dissemination or ascites, even for older patients.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Ascites; Dihydrouracil Dehydrogenase (NADP); Drug Combinations; Humans; Male; Oxonic Acid; Paclitaxel; Peritoneal Neoplasms; Peritonitis; Quality of Life; Stomach Neoplasms; Tegafur; Tomography, X-Ray Computed

The patient was a 66-year-old male, admitted and diagnosed as having advanced gastric cancer with peritoneal dissemination, leading to ascites and obstructive jaundice. After reducing the degree of obstructive jaundice, combination chemotherapy of S-1 80mg/m2/day(2 weeks administration and 1 week rest)and docetaxel(TXT)40mg/m2(day 1)was administered from February, 2008. After 3 courses of this regimen, CT revealed no evidence of ascites, and this chemotherapy was successively continued on an outpatient basis until June, 2009. After the relapse of ascites from July, 2009, combination chemotherapy of irinotecan(CPT-11)60mg/m2 and cisplatin(CDDP)30mg/m2 biweekly was performed as second-line chemotherapy, and the ascites disappeared again after around 2 courses of this regimen. This chemotherapy was continued on an outpatient basis until February, 2010. No major adverse reaction to either chemotherapy was observed. This case suggests that these chemotherapies, such as the combination chemotherapy of S-1 plus TXT as a first-line treatment and CPT-11 plus CDDP as the following second-line treatment, can be administered to an outpatient, can keep good patient's QOL and can be one of the effective chemotherapy options for advanced gastric cancer with peritoneal dissemination.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Ascites; Camptothecin; Cisplatin; Docetaxel; Drug Combinations; Fatal Outcome; Humans; Irinotecan; Male; Oxonic Acid; Peritoneal Neoplasms; Salvage Therapy; Stomach Neoplasms; Taxoids; Tegafur

A 49-year-old woman who complained of abdominal bloating and numbness in the bilateral lower limbs was diagnosed as advanced scirrhous gastric cancer with massive ascites. The biopsy specimen showed a poorly-differentiated adenocarcinoma. She was therefore treated with combined chemotherapy of tri-weekly docetaxel(40mg/m2, day 1, 22)and S-1(60mg/m2, day 1-14 with 1-week rest)for unresectable gastric cancer. After 5 courses, computed tomography showed no ascites. Furthermore, after 31 courses, the loss of ascites continued, and the thickening of the stomach walls was reduced. These findings suggested that a complete response in terms of Evaluation Criteria in Solid Tumors(RECIST)was obtained. The side effects throughout chemotherapy were Grade I anemia and Grade I alopecia. Docetaxel and S-1 chemotherapy may well be one of the effective treatments for advanced scirrhous gastric cancer.

Topics: Antineoplastic Combined Chemotherapy Protocols; Ascites; Biopsy; Docetaxel; Drug Combinations; Female; Humans; Middle Aged; Oxonic Acid; Peritoneal Neoplasms; Stomach Neoplasms; Taxoids; Tegafur; Tomography, X-Ray Computed

We report two cases of advanced gastric cancer successfully treated with combination S-1 and docetaxel (DOC) therapy. Case 1: A 43-year-old woman underwent radical total gastrectomy for advanced type 4 gastric cancer one and a half years ago. She was diagnosed as peritonitis carcinomatosa with much ascites, so the following combination chemotherapy was started. Case 2: A 53-year-old man underwent palliative gastrectomy for advanced type 3 gastric cancer with multiple lymph node metastases involving Virchow's metastases. After surgery, he received the following combination chemotherapy: DOC at the starting dose of 40 mg/m2 by iv infusion over 1 hour on day 1 and S-1 at the full dose of 80 mg/m2 daily for two weeks every three weeks. After administration of this combination therapy, the Case 1 gastric cancer with much ascites and the Case 2 gastric cancer with multiple lymph nodes metastases had entirely disappeared. Thereafter the 2 cases received therapy with S-1 alone. No recurrence in Case 1 has been seen with S-1 chemotherapy. Case 2 revealed a few lymph node swellings in the abdominal cavity, so he is undergoing combination therapy of DOC and S-1. The combination DOC and S-1 show a high degree of safety and can be a new tool for the management of advanced gastric cancer with peritoneal dissemination and Virchow's metastases.

Topics: Adult; Antimetabolites, Antineoplastic; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Ascites; Docetaxel; Drug Combinations; Female; Gastrectomy; Humans; Lymphatic Metastasis; Male; Middle Aged; Oxonic Acid; Peritoneal Neoplasms; Peritonitis; Stomach Neoplasms; Taxoids; Tegafur

Malignant ascites caused by gastric cancer are chemotherapy resistant and carry a poor prognosis. The efficacy of a regimen including intraperitoneal paclitaxel (PTX) was evaluated in 33 gastric cancer patients with ascetic fluid in the peritoneal cavity diagnosed with computed tomography (CT) scanning. Synchronous administration of intravenous (50 mg/m(2)) and intraperitoneal (20 mg/m(2)) PTX was performed via a subcutaneously placed intraperitoneal catheter on days 1 and 8, and S-1 was administered twice daily at 80 mg/m(2)/day for 14 consecutive days from day 1 to day 14, followed by 7 days of rest. The ascitic fluid volume was calculated with NIH Image J software using continuous CT images. After 2-4 treatment cycles, 23 (70%) patients showed reductions in their ascitic volumes of >50%. Ascites disappeared completely in 8 patients and were markedly reduced (to <3% of the original volume) in 4 of the 9 patients (44%) who initially had massive (>2,500 ml) ascites. Median overall survival was significantly better in patients with ascitic reduction. Weekly intravenous and intraperitoneal PTX combined with S-1 was highly effective in gastric cancer with malignant ascites. The change in ascitic fluid volumes determined by CT image measurements is a useful predictor of outcome in these patients.

Topics: Administration, Oral; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Ascites; Drug Administration Schedule; Drug Combinations; Female; Humans; Infusions, Intravenous; Injections, Intraperitoneal; Male; Middle Aged; Oxonic Acid; Paclitaxel; Peritoneal Neoplasms; Stomach Neoplasms; Survival Analysis; Tegafur; Tomography, X-Ray Computed

A 29-year-old man with a type 4 tumor, in the lower third of the stomach, and carcinomatous ascites was diagnosed by aspiration cytology of the ascitic fluid. Curative resection was considered impossible, and S1 (120 mg/d) and cisplatin (90 mg/d) were given for 21 days in 1 course. The cancer lesion showed marked remission (partial response), and the ascites completely disappeared after the fourth course. Twenty-five days after completion of the S1 treatment, laparoscopy-assisted total gastrectomy was performed. Histopathological examination showed no remnant cancer cells in the resected specimen and no lymph node metastases. The tumor was replaced with fibrosis having a granulomatous change. The patient's postoperative course was uneventful. The patient was continued with S1 monotherapy after surgery, and no signs of recurrence or metastases have been seen on any examination 12 months after the surgery.

Topics: Adenocarcinoma; Adult; Antimetabolites, Antineoplastic; Antineoplastic Combined Chemotherapy Protocols; Ascites; Cisplatin; Combined Modality Therapy; Drug Combinations; Endoscopy, Gastrointestinal; Gastrectomy; Humans; Laparoscopy; Lymph Node Excision; Male; Oxonic Acid; Stomach Neoplasms; Tegafur

The patient was a 54-year-old male with peritoneal dissemination and carcinomatous ascites of advanced gastric cancer. Although 4 months of temporary partial responses were obtained by a combination chemotherapy with TS-1 and DOC, retention of ascites appeared. Second-line combination chemotherapy with 5-FU and PTX was not effective, and we attempted to use intraperitoneal chemotherapy of low-dose CDDP. After 100 mg of CDDP had been administered, ascites almost disappeared. Then,intraperitoneal injection of low-dose CDDP and intravenous injection of 5-FU were given. Tumor marker decreased remarkably, and CT revealed reduction of peritoneal dissemination. These regimens seem to be effective in ambulant patients with advanced gastric cancer with peritoneal dissemination and carcinomatous ascites.

Topics: Ambulatory Care; Antineoplastic Combined Chemotherapy Protocols; Ascites; Ascitic Fluid; Cisplatin; Docetaxel; Drug Administration Schedule; Drug Combinations; Fluorouracil; Humans; Male; Middle Aged; Oxonic Acid; Paclitaxel; Peritoneal Neoplasms; Quality of Life; Stomach Neoplasms; Taxoids; Tegafur

We used combination therapy of S-1 and Paclitaxel to treat gastric cancer complicated by carcinomatous ascites and assessed the clinical results. The subjects were 8 patients who were gastric-cancer-ascites-positive, and they were treated by biweekly administration of S-1 orally, continuously for 2 weeks, and Paclitaxel on day 1 and day 8 of S-1 administration. The results showed disappearance of the ascites on diagnostic images in 37.5% (3/8) and PR in 50% (4/8) in terms of the main gastric cancer focus. An average 15 courses were conducted, and the overall adverse event rate was 87.5% (7/8). Hematologic toxicity occurred in 75.0% (6/8), and it was G3 or 4 in 37.5% (3/8). Non-hematological toxicity was confirmed in 75.0% (6/8), but none of it was G3 or 4. Although they were historical controls, we assessed the results of treatment in a conventional treatment group (control group; n=24) and the S-1 and Paclitaxel group (S-1+Paclitaxel group; n=8) by comparing the survival rates. MST in the S-1 and Paclitaxel group was 413 days, and the longest survival time was 1,148 days. The 1-year survival rate was 62.5%, and the 2-year survival rate was 37.5%. The survival rate in the S-1+Paclitaxel group was better than in the control group (p<0.001). We have reported this study because S-1+Paclitaxel therapy appears to be an important method of treating gastric cancer complicated by carcinomatous ascites.

Topics: Administration, Oral; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Ascites; Drug Administration Schedule; Drug Combinations; Female; Humans; Male; Middle Aged; Oxonic Acid; Paclitaxel; Stomach Neoplasms; Survival Rate; Tegafur

We encountered a resected case of advanced gastric cancer after successful chemotherapy. The patient remained alive in good condition without any signs of recurrence at 2 years and 8 months after surgery. The 40-year-old woman initially complained of low abdominal pain, which was diagnosed as gastric cancer with metastasis of ovaries and carcinomatous ascites. We administered TS-1 (100 mg/body/day) for 3 weeks followed by 2-week rest and CDDP (60 mg/body) on the 8th day of one cycle. After 3 cycles of treatment, carcinomatous ascites disappeared and the ovarian lesion was reduced. The patient underwent total gastrectomy, ileocecal resection, cholecystectomy and radical hysterectomy. The antitumor efficacy of the treatment was histologically Grade 2. We administered 17 cycles of TS-1 treatment, and the patient is alive in good condition at this writing. This shows that TS-1 and CDDP may have potent therapeutic efficacy in advanced gastric cancer patients. For the future, the safety and efficacious administration of TS-1 and CDDP should be examined further.

Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Ascites; Cholecystectomy; Cisplatin; Combined Modality Therapy; Drug Administration Schedule; Drug Combinations; Female; Gastrectomy; Humans; Hysterectomy; Ileum; Ovarian Neoplasms; Oxonic Acid; Remission Induction; Stomach Neoplasms; Tegafur

Paclitaxel was used as the first-line drug for treatment of a case with peritoneal recurrence of gastric cancer, accompanied by cancerous ascites. Because paclitaxel was ineffective, TS-1 was used as the second-line drug, resulting in disappearance of cancerous ascites on diagnostic imaging. This case was an 81-year-old male patient. In February 2004, he underwent resection of the pyloric side of the stomach (D 2) based on a diagnosis of advanced gastric cancer. CT scans, conducted in February 2005, revealed ascites, and a diagnosis of cancerous peritonitis was made on the basis of subsequent cyto-diagnostic findings. He was later hospitalized because of anorexia and difficulty with oral ingestion, and received paclitaxel therapy (60 mg/m(2)). Abdominal CT scans in May of the same year showed the disappearance of ascites. Thereafter, he was managed as an outpatient. In June of the same year, relapse of ascites was detected by CT scans, and exacerbation of ascites was seen in August. In October, paclitaxel was switched to TS-1 (80 mg/m(2)). CT scans, obtained at the end of two cycles of TS-1 therapy, revealed complete disappearance of ascites. This therapy was administered for 4 cycles in total. CT scans, performed at the end of each cycle of TS-1 therapy, confirmed the absence of ascites. At present (July 2006), the patient is managed on an outpatient basis. Our experience with this case suggests that if paclitaxel therapy fails to exert satisfactory efficacy, switching to second-line TS-1 therapy is a promising means of treating gastric cancer complicated by cancerous peritonitis.

Topics: Aged, 80 and over; Antimetabolites, Antineoplastic; Ascites; Drug Administration Schedule; Drug Combinations; Drug Resistance, Neoplasm; Gastrectomy; Humans; Male; Oxonic Acid; Paclitaxel; Peritoneal Neoplasms; Pylorus; Stomach Neoplasms; Tegafur

A 43-year-old woman who complained of abdominal fullness, appetite loss, and constipation was diagnosed as unresectable advanced schirrhous gastric cancer with left supra-clavicular lymph node metastases, massive ascites, rectal stenosis, and bilateral hydronephrosis due to peritoneal metastases. The biopsy specimen showed a poorly differentiated adenocarcinoma with signet-ring cells. After placement of the bilateral ureteral stents, she was treated with combined chemotherapy of biweekly paclitaxel (120 mg/m2, day 1, day 15) and TS-1 (80 mg/day, days 1-14 with 2-weeks rest). Subjective symptoms were relieved after one course of the chemotherapy. After 3 courses, computed tomography showed markedly reduced supra-clavicular lymph node metastases and no ascites. Radiographic and endoscopic examinations also demonstrated remarkable improvements in compliance of the gastric and rectal walls. These findings suggested that partial response on Response Evaluation Criteria in Solid Tumors (RECIST) was obtained. After the first course, the treatment was continued on an outpatient basis. There were no adverse effects over grade 2 throughout six courses of the chemotherapy. The biweekly paclitaxel and TS-1 chemotherapy may well be an effective treatment for advanced schirrhous gastric cancer with carcinomatous peritonitis.

Topics: Adult; Antimetabolites, Antineoplastic; Antineoplastic Agents, Phytogenic; Antineoplastic Combined Chemotherapy Protocols; Ascites; Carcinoma, Signet Ring Cell; Constriction, Pathologic; Drug Administration Schedule; Drug Combinations; Female; Humans; Lymphatic Metastasis; Oxonic Acid; Paclitaxel; Peritonitis; Pyridines; Rectal Diseases; Stomach Neoplasms; Tegafur

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.

Topics: Adenocarcinoma; Antineoplastic Combined Chemotherapy Protocols; Ascites; Cisplatin; Drug Administration Schedule; Drug Combinations; Female; Gastrectomy; Humans; Lymph Node Excision; Lymphatic Metastasis; Middle Aged; Oxonic Acid; Peritoneal Neoplasms; Preoperative Care; Pyridines; Stomach Neoplasms; Tegafur

We report a case in which TS-1 + paclitaxel (PTX) administration was effective for gastric cancer with malignant ascites. The patient was a 66-year-old male who received total gastrectomy, distal pancreatectomy and splenectomy. He complained of abdominal fullness and ascites 18 months later. The administered regimen of chemotherapy was TS-1 100 mg/day for two weeks, and PTX 120 mg/day on day 1 and 8 of TS-1 intake, followed by 1-week rest. Computed tomography (CT) showed complete loss of malignant ascites. The toxic events were grade 2 leukopenia and grade 2 alopecia.

Topics: Adenocarcinoma; Aged; Antineoplastic Combined Chemotherapy Protocols; Ascites; Cisplatin; Combined Modality Therapy; Drug Administration Schedule; Drug Combinations; Gastrectomy; Humans; Lymph Node Excision; Male; Oxonic Acid; Paclitaxel; Pyridines; Stomach Neoplasms; Tegafur

A 54-year-old woman with severe abdominal distention suffered from massive ascites. Cytological examination revealed adenocarcinoma cells, leading to a diagnosis of peritonitis carcinomatosa. Gastrointestinal fiberscopy (GIF) resulted in a histological diagnosis of type 4 advanced gastric cancer with signet-ring cell carcinoma. The clinical diagnosis was confirmed to be cT3(SE)cN1cM0cH0cP1, cStage IV gastric cancer, type 4, according to the Japanese classification of gastric carcinoma. The patient was treated with S-1 and low-dose cisplatin (CDDP) in order to alleviate the critical state of the disease. After the third cycle of the regimen, the clinical response of P1 was classified as a partial response (PR) according to the World Health Organization (WHO) criteria. The patient's appetite loss and abdominal discomfort were markedly alleviated. The patient experienced grade 2 leukocytopenia throughout the regimen. Surgery was performed. Ascites and peritoneal disseminated lesions were not observed, and cytological examination of the peritoneal washes was negative. Total gastrectomy with D1 lymph node dissection was performed, and the surgical diagnosis was sT3(SE)sN0sM0sH0sP0; sStage II. Microscopically, viable cancer cells were found to be scattered throughout the subserosal-serosal layers in the resected stomach. All of the samples from lesions that were potentially cancers involving peritoneal dissemination were diagnosed as fibrous scar tissues without any viable cancer cells. The patient is alive without recurrence at 10 months after surgery and 14 months after the initial chemotherapy. Thus, systemic chemotherapy with S-1/low-dose CDDP achieved desirable control of peritoneal disseminated cells, as assessed microscopically, suggesting that the regimen may be an effective strategy for the treatment of advanced gastric cancer with peritonitis carcinomatosa.

Topics: Ascites; Carcinoma, Signet Ring Cell; Cisplatin; Drug Combinations; Drug Therapy, Combination; Female; Humans; Middle Aged; Neoplasm Staging; Oxonic Acid; Pyridines; Stomach Neoplasms; Tegafur

The effects of a novel oral fluoropyrimidine derivative S-1 on peritoneal metastasis from gastric cancer were investigated. OCUM-2MD3 cells, a highly peritoneal-metastatic cell line, were injected intraperitoneally in nude mice. These mice were allocated to the following three groups (each group, n=10): the S-1 group, to which 10 mg/kg body weight of S-1 was administered per os daily; the FT group, to which 100 mg/kg body weight of tegafur (FT) was administered per os daily; the control group, to which no anticancer drug was administered. Drug administration was starting the day after inoculation. The median survival time of the S-1 group was found to be significantly longer than that of the FT group (30 days vs. 23 days; P<0.005) and the control group (vs. 24 days; P<0.005). The mean values of 5-fluorouracil (5-FU) concentrations in ascites of the S-1 group at 1-4 h were 414-580 ng/ml (n=5), and those of FT group were 70-87 ng/ml (n=5), with significant differences between the two groups at each observation time. The high CDHP concentrations in ascites of the S-1 group were observed at 1-6 h after drug administration. DPD was expressed strongly in fibrous tissue around peritoneal metastasis and weakly in tumor cells of peritoneal metastasis themselves. The high concentrations and long duration of 5-FU in the peritoneal cavity after S-1 administration suggest that S-1 may be effective against peritoneal dissemination. High concentrations of CDHP may prevent 5-FU degradation in peritoneal dissemination and its surrounding fibrous tissue.

Topics: Administration, Oral; Animals; Antimetabolites, Antineoplastic; Ascites; Dihydrouracil Dehydrogenase (NADP); Drug Combinations; Female; Fluorouracil; Injections, Intraperitoneal; Mice; Mice, Inbred BALB C; Mice, Nude; Oxonic Acid; Peritoneal Neoplasms; Pyridines; Stomach Neoplasms; Survival Rate; Tegafur; Tumor Cells, Cultured

The chemosensitivity of micrometastases in the peritoneal cavity to a 5-fluorouracil derivative (TS-1) was examined with a micrometastasis model featuring a human gastric cancer cell line tagged with the green fluorescence protein (GFP) gene in nude mice. Peritoneal metastases on the omentum and mesentery could be specifically visualized even when minute or dormant and also externally monitored noninvasively under illumination with blue light from 1 day after intraperitoneal (i.p.) injection of tumor cells. Metastatic deposits formed after i.p. injection of 2x10(6) tumor cells were significantly reduced by TS-1 in a dose-dependent manner (15-20 mg/kg), when it was orally administered from day 1 post-injection for 4 weeks (early administration). No such inhibition was evident after injection of 1x10(7) tumor cells. When 2x10(6) tumor cells given injection, the ascites-free period in TS-1-treated mice was significantly longer than in their untreated counterparts. Survival of TS-1-treated mice (5/15) was also significantly higher than the zero rate in controls (0/15), with 4 out of 5 surviving mice being free from peritoneal metastasis and the exception having only a few dormant metastases. In contrast, when TS-1 was administered starting from day 7 post-injection for 4 weeks (late administration), the survival and ascites-free period of the TS-1-treated mice were not significantly influenced. The results indicate that the chemosensitivity of peritoneal metastases to TS-1 is dependent on the number of i.p. tumor cells and the timing of drug administration. Peritoneal micrometastases at an early stage are most susceptible and can be effectively eliminated by oral administration of an anti-cancer agent, which leads to the longer survival and better quality of life (QOL) of the mice.

Topics: Administration, Oral; Animals; Antimetabolites, Antineoplastic; Ascites; Carcinoma; Cell Count; Dose-Response Relationship, Drug; Drug Combinations; Genes, Reporter; Green Fluorescent Proteins; Humans; Injections, Intraperitoneal; Luminescent Proteins; Male; Mesentery; Mice; Mice, Nude; Omentum; Oxonic Acid; Peritoneal Neoplasms; Prodrugs; Pyridines; Stomach Neoplasms; Tegafur; Tumor Cells, Cultured; Xenograft Model Antitumor Assays

A 62-year-old man with carcinomatous ascites more than 5 years after early gastric cancer operation was admitted to our hospital because of suspected pancreatic cancer, and was diagnosed with a relapse of the gastric cancer. TS-1 was administered at a dose of 120 mg/day. At the end of 1 course a partial response of a decrease of tumor markers and ascites and improvement of QOL was achieved, and the patient was followed in the outpatient clinic. The current case suggests that TS-1 may have a potent therapeutic efficacy in cases of gastric cancer relapse with carcinomatous ascites.

Topics: Adenocarcinoma; Antimetabolites, Antineoplastic; Ascites; Drug Administration Schedule; Drug Combinations; Humans; Male; Middle Aged; Neoplasm Recurrence, Local; Oxonic Acid; Peritonitis; Pyridines; Stomach Neoplasms; Tegafur

We treated a patient with inoperable advanced gastric cancer and malignant ascites by combination chemotherapy of TS-1 and biweekly paclitaxel (TXL). After two courses the ascites had disappeared and the primary tumor was reduced. TS-1 (80 mg/body/day) was administered for 21 days followed by 7 days rest and TXL (100 mg/body) was administered on days 1 and 14 as one course. The patient could not eat at the time of hospitalization, but at the time of the second course he could eat a full serving of rice porridge. Grade 2 anemia and leukopenia were the only adverse reactions observed; no major adverse reactions were observed. These results suggest that with TS-1 and TXL combination chemotherapy, patients with advanced gastric cancer can achieve a marked improvement in quality of life.

Topics: Adenocarcinoma; Aged; Antineoplastic Combined Chemotherapy Protocols; Ascites; Drug Administration Schedule; Drug Combinations; Esophageal Neoplasms; Humans; Male; Neoplasm Invasiveness; Oxonic Acid; Paclitaxel; Pyridines; Quality of Life; Stomach Neoplasms; Tegafur; Treatment Outcome