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.     

A case of a nonresected gastric cancer with peritoneal dissemination maintained on TS-1 and docetaxel combination chemotherapy with good QOL

In general, treatment for gastric cancer with peritoneal dissemination or recurrent gastric cancer is outside the scope of surgery. The efficacy of new anti-cancer drugs such as TS-1 system was revealed in a controlled study by comparing treatment with non-treatment groups. We performed chemotherapy of TS-1 and docetaxel (TXT) in the outpatient clinic on a 72-year-old nonresected gastric cancer patient accompanied by peritoneal dissemination. Although no killer cell effect was recognized, the patient clinically achieved good QOL by this method for one year and seven months. In conclusion, we reported a treatment method for nonresected gastric cancer, which was treated only on an outpatient basis. The course of this case closely resembled the tumor dormancy therapy performed by Takahashi et al.     

A case of peritoneal dissemination disappeared by CPT-11 + TS-1 combination chemotherapy

A patient is a 35-year-old man. By a diagnosis of descending colon cancer, descending colon ablative operation and D1 lymph node dissection were performed on April 22, 2004. It was P3H0N1SE, Stage IV in perioperative findings. Abdominal CT showed peritoneal dissemination of 1.7 cm at the right under the abdominal wall wound and 1.2 cm in the rectovesical pouch on May 18, 2004. CPT-11 + TS-1 combination chemotherapy was started on June 22nd. In the five weeks of the combination chemotherapy, continuous infusion of CPT-11 (150 mg/body day 1 and 15) was twice administered, and oral administration of TS-1 (120 mg/body/day) was given for 3 weeks (day 1-21). Peritoneal dissemination disappeared after the two-course end, and we judged it as CR. Furthermore, we were certain that we obtained CR after the three course end. The adverse event was only neutropenia of grade 1. The fourth course was not administered, but recurrence has not been observed. Abdominal CT showed no recurrence on March 3, 2005 since the combination chemotherapy ended 6 months ago.     

A case of nonresected gastric cancer with peritoneal dissemination maintained on TS-1, cisplatin (CDDP) and docetaxel combination chemotherapy with good QOL

A 64-year-old woman was admitted to the hospital for abdominal fullness and constipation. In the pelvic cavity, an abdominal CT scan revealed massive ascites showing malignancy on histological examination. Upper GI endoscopy revealed type 3 gastric cancer from the anglus to the cardia. A barium-enema showed a stenotic lesion at the sigmoid colon due to peritoneal dissemination. An abnormally high CA125(1,400 mg/ml) level was detected in serum. We performed systemic chemotherapy of TS-1, CDDP and peritoneal infusion of docetaxel on the nonresected gastric cancer with peritoneal dissemination. After 2 cycles, cytology of ascites revealed no malignancy, and the serum CA125 value regained its normal level. After 3 cycles, the killer cell effect was recognized by laparoscopic examination and the stenotic change of sigmoid colon had almost disappeared. The patient clinically achieved good QOL by this method, which was very effective for nonresected gastric cancer with peritoneal dissemination.     

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.     

Oral fluoropyrimidine anticancer drug TS-1 for gastric cancer patients with peritoneal dissemination

The survival of gastric cancer patients with peritoneal dissemination is dismal and surgical intervention is rarely indicated. The usefulness of TS-1, a novel oral anticancer drug, composed of tegafur, gimestat and otastat potassium at a molar ratio of 1:0.4:1, and the role of surgical intervention for this condition was studied. Among gastric cancer patients with peritoneal dissemination, 18 treated during September 1999 to March 2001, and 16 before March 1999, were classified into the TS-1 group and control group, respectively, and survival was compared. TS-1 was administered orally twice daily, at a dose of 80 mg/m2/day, for 28 days followed by 14 days without treatment. This cycle was repeated. There was no difference in clinicopathologic factors, including surgical intervention, between the two groups. Eleven patients of the control group had chemotherapy using fluoropyrimidine. Grade 3-4 adverse reactions caused by TS-1 occurred in 1 patient. Survival was better in the TS-1 group than control group (p=0.0008), with median survival of 257 vs. 118 days. The median discharged period of patients of the TS-1 group with a performance status 0-2 on the Zubor scale was 211 days. TS-1 was effective to prolong the survival of gastric cancer patients with peritoneal dissemination. In this series of cases, surgical intervention to establish the route of oral administration was essential for this treatment.     

Neoadjuvant chemotherapy for gastric cancer with peritoneal dissemination

An early detection and treatment of gastric cancer with peritoneal dissemination are rather difficult so that a clinical trial has been neglected. Therefore, we introduced a pre-operative peritoneal lavage diagnosis for gastric cancer patients with serosa-invaded tumors. Neoadjuvant chemotherapy was introduced to patients with positive cytology and with no non-curative factors except peritoneum. The neoadjuvant chemotherapy followed by surgery was done safely. The patients with the disappearance of CY and P factors due to neoadjuvant chemotherapy had a better prognosis than those with positive results of CY or R However, many of the patients with negative results from peritoneum eventually suffered a peritoneal recurrence. We started another protocol study with S-1 and an intra-peritoneal chemotherapy using docetaxel. The efficacy in the protocol result will be expected.     

A case of recurrent gastric cancer with peritoneal dissemination successfully treated over 1 year 8 months with combined chemotherapy of paclitaxel and TS-1

We report a case of gastric cancer with peritoneal recurrence that responded to chemotherapy with paclitaxel and TS-1. A 62-year-old woman, who underwent total gastrectomy for advanced gastric cancer 2 years and 6 months ago, was admitted to our hospital with a chief complaint of abdominal distention and intestinal obstruction due to a large amount of ascites. Cytology of ascites revealed peritoneal dissemination, and chemotherapy with bi-weekly paclitaxel (90 mg/body) was begun. Clinical symptoms, including ascites and intestinal obstruction, were improved only after the second administration of paclitaxel. As she was able to take food orally, she was placed on combined chemotherapy consisting of tri-weekly paclitaxel (9 0 mg/body-120 mg/body: day 1) and TS-1 (80 mg/day: day 1-14) and 1 or 2 weeks rest. The patient had no signs or symptoms of peritoneal metastasis or toxicity except for general fatigue and watery eyes 1 year and 8 months after the diagnosis of peritoneal metastasis. Paclitaxel and TS-1 therapy was thought to be an effective chemotherapy against recurrent gastric cancer with peritoneal dissemination.     

A case of advanced gastric cancer with peritoneal dissemination effectively treated by combined chemotherapy of paclitaxel (TXL) and TS-1

The patient was a 49-year-old woman. Chemotherapy was conducted combining paclitaxel (TXL) and TS-1 under the diagnosis of non-resectable advanced gastric cancer with peritoneal dissemination. The administration schedule was as follows: 60 mg/m2 of TXL on days 1, 8 and 15 intravenously and 120 mg/day of TS-1/on days 1 5, 8-12, and 15-19 orally. One cycle lasted for 5 weeks. Grade 1 peripheral neuropathy was noted, but no other serious adverse reaction occurred. Ascites fluid was reduced after completion of the 1st cycle, and the therapeutic efficacy was rated as PR. Abdominal fullness was relieved shortly after starting the treatment, making it possible to conduct treatment on an ambulatory basis in the 2nd and subsequent cycles. At present, 6 months after starting chemotherapy, there is no evidence of relapse or adverse reactions that require intervention. Chemotherapy is being continued on an ambulatory basis. Combination of TXL and TS-1 is expected to show good therapeutic efficacy and improve patients' QOL in patients with gastric cancer associated with peritoneal dissemination.     

Intraperitoneal chemotherapy in gastric cancer patients with peritoneal dissemination

Peritoneal dissemination is one of the non-curative factors in gastric cancer and colon cancer. Although many treatments have been conducted for peritoneal dissemination, no standard chemotherapy has yet been established. For sometime we had used continuous hyperthermic peritoneal perfusion (CHPP)for peritoneal dissemination in gastric cancer and colon cancer. CHPP has a marked survival benefit for scirrhous type gastric cancer patients without liver metastasis. Patients with prophylactic CHPP have significantly better prognoses than those without prophylactic CHPP, and therapeutic CHPP has a survival benefit for gastric cancer patients with slight to moderate peritoneal dissemination (P 1-2). But CHPP has no significant prognostic benefit for gastric cancer patients with severe peritoneal dissemination (P 3). Therefore, a new cancer treatment is needed for those patients. On the other hand, many kinds of anticancer agents, including cisplatin, via intraperitoneal (ip) administration have been tried thus far for peritoneal dissemination therapy. Especially, intraperitoneal taxane anticancer agent is very effective for the treatment and local control of severe peritoneal dissemination in gastric cancer. A phase I/II study of taxane anticancer agents via ip administration should be tried in gastric cancer patients with peritoneal dissemination.     

Long survival and effective treatment of unresectable gastric cancer by TS-1 based chemotherapy with a sequential combination

We report a case of peritoneal cancer dissemination and cytological appearance of cancer cells with Type 4 gastric cancer. Treatment with unichemotherapy and combination chemotherapy with TS-1 proved successful. The patient was a 58-year-old female,who complained of abdominal pain. She was diagnosed as unresectable Type 4 gastric cancer, T 3 NxH 0 P 1 CY 1 M 0, Stage IV (cytology: Class V). Thirteen days after surgery, chemotherapy with TS-1 (80 mg/body/day, 4 weeks) at 2-week intervals in 1 course was performed. However, due to side effects with marrow restraint of grade 1, we changed to the following chemotherapy regimen: TS-1 (80 mg/body/day, 2 weeks) at 4-week intervals as 1 course (23 courses in total). After 16 courses, a partial response (PR) was noted. As additional therapy to recover tumor marker (CA19-9) after 21 courses, combination chemotherapy with TS-1 (80 mg/body/day, 2 weeks) and CDDP (25 mg/body/day, day 1, 8, 15 drip infusion) was performed as one course. This chemotherapy was then performed in 3 courses and tumor markers did not deteriorate, so we changed docetaxel (DOC) (50 mg/body/day(day 1)) to CDDP, and tumor markers returned to the normal value. No recurrence and no side effects appeared (hematological or non-hematological) during this combination chemotherapy.     

The clinical effect of TS-1 in advanced and recurrent gastric cancer with peritoneal dissemination

Eighteen patients with far advanced and recurrent gastric cancer with peritoneal dissemination were treated with a novel oral anticancer drug, TS-1, and assessed according to clinical effect. TS-1 was administered at a dose of 80-120 mg/day. One course consisted of consecutive administration of TS-1 for 28 days followed by 14 days rest. The 1- and 2-year survival rates and median survival time after administration of TS-1 were 63.2%, 23.7% and 437 days, respectively. Eight patients (44.4%) survived for 1 year or more. Adverse reactions consisted of reduction in hemoglobin level and hyperbilirubinemia at grades 3 and 4, which were observed in 3 patients and 1 patient, respectively. TS-1 is a promising drug for gastric cancer with peritoneal dissemination.     

A case of gastric cancer with peritoneal dissemination who achieved five-year survival by successive treatments with TS-1 alone and in combination with other drugs

The patient was a 65-year-old male with gastric cancer. Peritoneal disseminations were detected during distal gastrectomy. CDDP and mitomycin C were administered into the peritoneal cavity. Administration of TS-1 was begun and continued without adverse effects. After 33 months, a high dose of CDDP was administered twice in combination with TS-1, because elevation of serum CEA levels and paraortic lymphnode swelling were observed for the first time. A partial response was obtained, but an elevation of CEA was seen again in three months. We then tried weekly administration of paclitaxel, and a complete response was achieved in three months. After three months'rest from chemotherapy, a third regrowth of the tumor was observed. Paclitaxel was ineffective, and so we opted for weekly administration of low-dose CDDP combined with TS-1, which led to the third recovery. Biweekly administration of CPT-11 combined with TS-1 followed the low-dose CDDP and was successfully continued five years after the surgery. The treatment course in this patient was fully suggestive for patients with advanced or recurrent gastric cancer because the use of newly available chemotherapeutic agents in turn was effective at each recurrence of the tumor and achieved five-year survival with minimal hospitalization.     

A case of gastric cancer with peritoneal dissemination responding to combination chemotherapy with oral fluoropyrimidine and weekly paclitaxel

We report a case in which combination chemotherapy with oral fluoropyrimidine and weekly paclitaxel was effective for gastric cancer with peritoneal dissemination. A 44-year-old woman suffering from advanced gastric cancer with peritoneal dissemination underwent total gastrectomy. After surgery, combination chemotherapy with doxifluridine plus weekly paclitaxel was administered on an outpatient basis, and was effective without any sign of relapse of the disease for a year. However, she complained of dull abdominal pain, and ascites was observed 13 months after surgery. She received combination chemotherapy with S-1 plus weekly paclitaxel. The ascites decreased after 3 courses of the chemotherapy. No major adverse effect was observed except for grade 1 anemia and grade 2 hair loss. She has been well with the chemotherapy on an outpatient basis 18 months after surgery.     

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 of remnant gastric cancer with multiple bone metastasis and peritoneal dissemination; efficacy of combination therapy of docetaxel and TS-1

A 69-year-old female underwent radical surgery for advanced gastric cancer (Stage IIIA) 7 years ago. She was diagnosed as remnant gastric cancer with multiple bone metastasis and peritoneal dissemination. Treatment with docetaxel and TS-1 was started with the following regimen: daily oral administration of 100 mg/body TS-1 for 14 days, followed by a 7 day rest and infusion of 40 mg/m2 docetaxel on day 1. Two months after the initial administration of docetaxel/TS-1, the sites of the remnant gastric cancer and bone metastasis were reduced in size, and the ALP returned to almost the normal level. The site of peritoneal dissemination had disappeared. Currently (nine months after diagnosis), she is undergoing therapy with TS-1. The combination of docetaxel and TS-1 can be a new tool for the management of gastric cancer with bone metastasis.     

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 of advanced colon cancer with peritoneal dissemination completely responding to TS-1

A 55-year-old man was referred to us after transverse colostomy for intestinal obstruction caused by descending colon cancer with peritoneal dissemination. The colon lesion was palpated as a well-defined hard mass in the left lower abdomen and the disseminated lesion as a hard mass with an unclear border in the right lower abdomen. CEA level was 917 ng/ml at admission. Left hemicolectomy was performed for tumor reduction and TS-1 of 120 mg/day was started 6 days after surgery (4 weeks administration followed by a 2-week rest period). Administration discontinued due to nausea 4 weeks after commencement of the therapy, and restarted as a 2-week administration followed by a 2-week rest period. There has been no adverse reaction since then. Twenty-seven weeks after surgery, CEA level was reduced to 47 ng/ml and peritoneal dissemination was found to have disappeared upon physical examination and computed tomograph. TS-1 is expected to be an effective agent for the treatment of colon cancer with peritoneal dissemination.     

Safety and efficacy of chemotherapy using TS-1 followed by paclitaxel for advanced or recurrent gastric cancer with peritoneal dissemination

There has been no standard treatment for gastric cancer with peritoneal dissemination. We have used TS-1 followed by paclitaxel for advanced or recurrent gastric cancer patients with peritoneal dissemination since January 2002. Twenty-three patients were enrolled to our prospective study and 19 of 23 patients completed the protocol. There were less severe adverse events concerning paclitaxel despite of the second line therapy of TS-1, and 80 percent of all therapeutic courses was at an outpatient clinic. The median time to progression was 199 days. The median survival time was 363 days in all the enrolled patients, and was 436 days in 19 patients who completed the protocol. Chemotherapy using TS-1 followed by paclitaxel is considered to be safe and effective for gastric cancer with peritoneal dissemination.