A case of advanced gastric cancer resistant to S-1 successfully treated with weekly administration of paclitaxel

A 62-year-old female was diagnosed with type 2 advanced gastric cancer in May 2003. Pathological examination showed a poorly differentiated carcinoma. Computed tomography (CT) revealed paraaortic lymph node metastasis, duodenal metastasis and ascites due to peritoneal dissemination. Chemotherapy with CDDP+S-1 was started and continued. After the chemotherapy, there were progressive diseases. Therefore, paclitaxel (PTX) was administered at a dose of 80 mg/m2/day for 3 weeks followed by a week rest. Clinical symptoms were relieved, and CT scan revealed metastatic lymph nodes were reduced after 4 cycles. After 13 cycles, MRI revealed a solitary brain mass was detected. She was resected for a right temporal-occipital brain metastatic tumor, and local cerebral irradiation was performed. After this operation, she was diagnosed with brain metastasis from advanced gastric cancer. The procedure was interrupted for about 6 months. After rehabilitation, PTX treatment was restarted as 14th cycle. She has survived without recurrence more than 30 cycles after the resection. A weekly administration of PTX may be a promising regimen as second-line chemotherapy for S-1 resistant recurrent gastric cancer.     

A case of recurrent esophageal cancer successfully treated with weekly paclitaxel in combination with radiotherapy

A 48-year-old man underwent subtotal esophagectomy for pStage III (pT 3 pN 3) thoracic esophageal carcinoma on June 20, 2002, in combination with chemotherapy (5-FU 500 mg/day day 1-14, CDDP 10 mg/day day 1-14, VDS 3 mg on days 1 and 8) before and after the operation. Recurrence was seen 7 months after the operation in right pleura and lower mediastinum. Chemo (same regimen)-radiotherapy (50 Gy) was then performed but without effect. Thereafter, lung and upper mediastinal metastases were found, and weekly administration of paclitaxel (70 mg/m2, day 1, 8, 15, q 4w) was initiated in combination with radiotherapy (40 Gy). Two cycles of treatment resulted in PR, and CR was achieved after the 8th cycle was completed. Although treatment was terminated after the 12 th cycle due to development of peripheral neuropathy (grade 2), CR was still maintained 8 months after the completion of treatment. These results suggested the effectiveness of the treatment in cases that show resistance to conventional 5-FU-based chemotherapy.     

A case of non-curatively resected scirrhous gastric cancer successfully treated over 2 years with weekly administration of paclitaxel

We report a patient with far-advanced gastric cancer treated by weekly administration of paclitaxel (TXL) over 2 years. The patient was a 66-year-old female with peritoneal metastasis and remarkable lymph node metastasis of scirrhous gastric cancer. She underwent a non-curative resection with total gastrectomy and splenectomy in May 2002. Postoperative chemotherapy with TS-1 (80 mg/body) was performed. Due to grade 4 neutropenia and grade 2 anorexia, this treatment could not be continued. Three months after surgery, the tumor marker (CA19-9) had elevated to an abnormal level. Alternatively, TXL was administered at a weekly dose of 70 mg/m2 for 3 weeks followed by 6 weeks rest from September 2002. The tumor marker (CA19-9) gradually decreased to the normal level. Because of the long rest interval, 10 courses of treatment could be continued, and the patient has been alive over 2 years with the cancer controlled. There have been few effective chemotherapies for gastric cancer with peritoneal metastasis. Weekly paclitaxel therapy is considered to be effective for the treatment of advanced scirrhous gastric cancer with peritoneal metastasis.     

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 case of advanced gastric cancer successfully treated with S-1 and paclitaxel followed by curative resection

A 59-year-old man diagnosed with Stage IV advanced gastric cancer due to pancreatic invasion(T4)and splenic hilum lymph node metastasis(N3)was initially treated with neoadjuvant chemotherapy using S-1 and CDDP. However, it was discontinued because the tumor marker increased after 1 course. Instead of S-1 and CDDP, S-1 and paclitaxel were then administered. After 4 courses, CT scan revealed reduced tumor size and the disappearance of splenic hilum lymph node swelling that indicated PR of the chemotherapy. Moreover, serum CEA was remarkably decreased to 77 ng/mL from 1,092 ng/mL. He could undergo subtotal gastrectomy(Billroth II)with lymph node dissection(D2)and cholecystectomy. Histopathological examination revealed Stage II (pT2(SS), pN1, CY0, ly1, v2)advanced gastric cancer that showed good effect of S-1 and paclitaxel. At this writing (October 2007), the patient has remained free of disease for more than 1 year and 6 months with good nutrition. Neoadjuvant chemotherapy using S-1 and paclitaxel for advanced gastric cancer seems to have been effective.     

A case of recurrent gastric cancer successfully treated with TS-1

A patient with recurrent gastric cancer which infiltrated the pelvic muscle after the treatment of paraaortic lymph node and ovarian metastases was successfully managed by a novel oral anticancer drug, TS-1. TS-1 was administered at a dose of 80 mg/day. One course consisted of two repetitions of consecutive administration of TS-1 for 14 days and withdrawal of TS-1 for 14 days. Adverse reactions were mild and the patient did not request hospitalization after two courses had been completed. Subjective symptoms such as difficulty in walking improved after one week and a partial response was obtained after 2 weeks of treatment. At the end of 4 courses we could remove an indwelling pyelocatheter for the ureter stricture. As of 14 months after the beginning of administration of TS-1, the patient is being treated as an outpatient and has attained a better QOL than before.     

Two cases of recurrent breast cancer successfully treated with paclitaxel weekly therapy

The patients were a 57-year-old and a 38-year-old woman who had supraclavicular lymph node and multiple lung metastases from breast cancer. They were given 3 and 4 courses of paclitaxel (TXL) weekly therapy (80 mg/m2, day 1, 8, 15, repeated every 4 weeks). One patient had received docetaxel (TXT) and CEF therapy previously. There were no severe adverse effects except leukopenia, neutropenia and alopecia. The weekly TXL therapy brought complete remission against the supraclavicular lymph node and multiple lung metastases. The durations of the response to this weekly therapy were 15 and 5 months, respectively, and their effects have continued to the present. We believe that the weekly TXL therapy is a well-tolerated, feasible and safe administration schedule on an outpatient basis, and improves the patient's quality of life. Furthermore, we suggest the possibility of TXL being effective against both TXT and anthracycline-resistant breast cancer.     

Case of advanced gastric cancer successfully treated with chemotherapy of weekly paclitaxel

We report a case of gastric cancer with ascites treated with chemotherapy. The patient is a 67-year-old male. Combination chemotherapy of S-1 and CDDP was given as the first-line treatment. However, the symptoms did not improve with that regimen, so we decided to change the chemotherapy to paclitaxel as second-line treatment. After 4 cycles, CT scan revealed decreasing ascites and endoscopy a reduction of the primary tumor. The patient has maintained a condition of decreasing ascites with improvement of QOL for 8 months. This regimen is considered effective treatment for unresectable gastric cancer.     

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.     

单周方案紫杉醇单药治疗在晚期胃癌应用的进展

晚期胃癌给予化疗加支持治疗，患者的生存率和生活质量都较单独给予支持治疗高。目前，在晚期胃癌治疗中，紫杉醇类的药物是最有前途的细胞毒药物之一。紫杉醇的单药使用，特别是低剂量每周的单药治疗，显示出了令人振奋的作用，且毒副反应较低，起效快，迅速缓解症状，对于一些老年、生存状况差、不适于进行联合化疗，甚至失去常规化疗指征的晚期胃癌患者，不失为一种可供选择的治疗方法。本文着重介绍小剂量每周紫杉醇单药治疗晚期胃癌的一些临床报道。     

A case of effective weekly paclitaxel administration for advanced gastric cancer

A 74-year-old man was admitted to our hospital with severe anemia. Endoscopic examination revealed a type 3 advanced gastric cancer. Abdominal computed tomography revealed massive lymph node metastasis(N3). We performed distal gastrectomy(noncurative resection)because anemia had progressed. After operation, we administered S-1/CDDP combination chemotherapy. Although he received two courses of S-1/CDDP, renal dysfunction was found. Afterwards a rise in tumor marker(CEA)occurred, so we changed to chemotherapy with weekly paclitaxel. Abdominal computed tomography then revealed a complete response(CR)after the chemotherapy was completed. At present, 7 years after the operation, the patient remains free of a rise in tumor markers and presents no evidence of a recurrence.     

A case of effective weekly paclitaxel administration for metastatic gastric cancer

We report a case of effective weekly paclitaxel (TXL) administration for metastatic gastric cancer. TXL (80 mg/m2) was infused over 1 hour after short premedication on an outpatient basis. Administration was continued for 3 weeks followed by 1 week rest. A 74-year-old man was diagnosed with recurrence 49 months after surgery for gastric cancer. He was treated with 5-fluorouracil and cisplatin, and thrombocytopenia (grade 3) and creatinin elevation (grade 1) were observed and assessed as progressive disease 2 months after the treatment. We attempted weekly TXL administration and after 5 courses assessed the patient as having a partial response. The treatment is ongoing. The toxic event was leukopenia (grade 2), with no episode of thrombocytopenia. The patient did not complain of nausea or vomiting, and his quality of life was fair during the treatment. Weekly TXL administration is a useful treatment for metastatic gastric cancer.     

A case of effective weekly paclitaxel administration for metastatic gastric cancer

We report a case of long-term effectiveness of weekly paclitaxel (TXL) administration for metastatic gastric cancer. TXL (80 mg/m2) was infused over 1 hour after short premedication on an outpatient basis. Administration was continued for 3 weeks followed by 1 week rest. A 61-year-old man was diagnosed as having gastric cancer with multiple liver metastases. He was treated with FP therapy and irinotecan/cisplatin administration and both therapies were assessed to result in progressive disease. We attempted weekly TXL administration and assessed a long period of no change after 6 courses. The treatment is ongoing. The toxic events were peripheral neuropathy and alopecia (grade 2), with no episodes of leukopenia, nausea and vomiting. The patient's quality of life was fair during the treatment. Weekly TXL administration is a useful treatment for metastatic gastric cancer.     

A case of multiple liver metastases of gastric cancer successfully treated by combination chemotherapy of S-1 and paclitaxel

A 54-year-old man underwent distal gastrectomy for early gastric cancer in September 2002. CT performed 6 months after the operation revealed liver metastases, and they were resected. Hepatic arterial infusion therapy of 5-FU was performed; however, multiple liver metastases appeared in October 2003. We added arterial infusion of CDDP to 5-FU, but liver metastases increased. We then applied a combination chemotherapy of S-1 and paclitaxel from February 2004. Subsequently, stable disease continued, and after 67 courses of S-1 plus paclitaxel, we changed the administration to S-1 alone from August 2009. After that, liver metastases did not increase, so we discontinued chemotherapy on August 2010, followed by observation. Progression of liver metastases has not been to date.     

A case of recurrent gastric cancer successfully treated with S-1 plus CDDP (divided into small dosages)

A 75-year-old man was found to have a type 2 gastric cancer on the pyloric side. In February 2006, he underwent gastrectomy, followed by oral medication with 300 mg/day of UFT on an ambulatory basis. In June 2006, the lymph nodes in the hepatoduodenal ligament became swollen. The patient was started on S-1 monotherapy(S-1 was given orally 80 mg/body/ day for the first 4 weeks of a 6 week cycle). S-1 was given for 6 courses over 9 months. In March 2007, further swelling of the lymph nodes in the hepatoduodenal ligament(PD)and a CEA level increase were noted, and therapy of S-1 combined with CDDP(divided into small dosages)was started in April 2007. Since then until July 2009, 16 courses of S-1 combined with CDDP therapy were completed. During this period(for 2 years and 3 months), the lymph nodes in the hepatoduodenal ligament remained generally unchanged(SD)in imaging observations. However, no new lesions were discovered, The CEA level was reduced and the patient remained free of clinical symptoms. While there are no adverse effects and he could receive continued care on an ambulatory basis. In September 2009, obstructive jaundice was found, and it was treated by biliary stenting. He suffered repeated bouts of cholangitis, which contributed to the exacerbation of his systemic condition. The patient succumbed in January 2010. S-1 monotherapy was found to be ineffective but a combination therapy of S-1 plus CDDP(divided into small dosages)was effective in dealing with a recurrence of the gastric cancer. A case was presented in which such treatment allowed a patient with recurrent gastric cancer to survive for 3 years and 11 months following surgery.     

A case of recurrent gastric cancer successfully treated with radiation therapy

We report a case of recurrent gastric cancer that was effectively controlled with radiation therapy. A 63-year-old man underwent total gastrectomy, cholecystectomy and D2 dissection in February 2006 for early gastric cancer in the upper third area that was diagnosed with papillary adenocarcinoma and Stage IA (T1 (SM), N0, H0, P0, CY0, M0). He underwent lateral segmentectomy of the liver for liver metastasis of S2/3. He suffered from No. 12 lymph node(LN)metastasis in February 2009, so CPT-11, next to S-1, was administered. Portal tumor thrombosis (PTT) and liver S8 metastasis were observed in September 2009. First, chemoradiotherapy (CRT) ( S-1 80 mg/body+total of 65 Gy per 26 Fr) for #12 LN and PTT was performed and, in turn, stereotactic radiation therapy (SRT: total of 52.8 Gy per 4 Fr) was performed. A complete response in all of tumors was noted and he was presently alive with no sign of recurrence after 19 months after CRT and SRT. Grade 3 or 4 adverse events were not recognized. It is thought that radiation therapy is one of effective treatments for localized metastasis from gastric cancer.     

S-1 combined with weekly paclitaxel in patients with advanced gastric cancer

S-1 Combined with Weekly Paclitaxel in Patients with Advanced Gastric Cancer: Masahiro Gotoh, Shin-ichiro Kawabe and Hiroya Takiuchi (Dept. of Gastroenterology, Osaka Medical College) Summary Both paclitaxel and S-1 have been identified as an effective agent for the treatment of gastric cancer. Furthermore, weekly paclitaxel was found to have a better toxicity profile and to be as effective as an equivalently dosed conventional schedule of delivery every 3 weeks. Osaka Gastrointestinal Cancer Chemotherapy Study Group (OGSG) conducted the phase I/II study of weekly paclitaxel combined with S-1. S-1 was given orally at a fixed dosage of 40 mg/m2 bid for 14 consecutive days, followed by a week rest. Paclitaxel was scheduled to be given intravenously on days 1 and 8. The MTD of paclitaxel was presumed to be 60 mg/m2 because 50.0% of patients (2/4) developed DLTs (mainly grade 3 anorexia). Therefore, the RD of paclitaxel was estimated to be 50 mg/m2. This combination treatment was demonstrated to exhibit a tolerable toxicity profile with a high antitumor activity of 48% (14/29) and MST of 417 days. This regimen is investigated in a randomized phase II trial and may yet become a test arm in future phase III trials.     

A case of advanced breast cancer successfully treated with multi-disciplinary therapy and S-1 administration

We report a case of advanced breast cancer (T4b, N3c, M1) achieving a significant improvement on QOL by multi-disciplinary therapy and S-1 administration. The patient was a 59-year-old woman who had ulcerative breast lump with bleeding. A core needle biopsy for breast tumor led to a diagnosis of an invasive ductal carcinoma negative for estrogen receptor, progesterone receptor, and HER2/neu protein expression. The aspiration biopsy cytology was performed from skin lesion, the diagnosis was class V. She received 6 cycles of tri-weekly CEF (C: 500 mg, E: 60 mg, F: 500 mg/m2) therapy. The effect of the breast tumor was partial response, and the bleeding from the breast lump was improved. But the response from metastatic skin tumor was less satisfactory. We performed a radiation therapy (20 Gy) to metastatic skin tumor, and the lesion disappeared after the radiation therapy. Then, we tried docetaxel, but the side effect appeared. So, we started administering S-1 after docetaxel. One year later, she was estimated to be in the long stable disease. Multi-disciplinary therapy can improve a patient QOL and the clinical outcomes in Stage IV advanced breast cancer.     

A case of extraovarian primary peritoneal carcinoma successfully treated with weekly paclitaxel

We report the use of paclitaxel in the successful treatment of a 74-year-old patient with extraovarian primary peritoneal carcinoma and acute renal failure caused by intraperitoneal cisplatin. The histological diagnosis was papillary serous adenocarcinoma. Paclitaxel was given intravenously at 70 mg/m2 in a 1-hour infusion weekly for 6 consecutive weeks followed by 2-weeks rest (one cycle). Toxicities including neutropenia and neurotoxicity were mild. She showed a clinical response after three cycles, and then underwent secondary cytoreductive surgery after which she received one additional cycle of therapy. She enjoyed a favorable quality of life without evidence of disease for 16 months after the completion of this therapy. Weekly 1-hour paclitaxel (70 mg/m2) was well tolerated, yet was effective for extraovarian primary peritoneal carcinoma.     

A case of advanced gastric cancer successfully treated with docetaxel and S-1 combined therapy

A 46-year-old woman with lower abdominal distension was diagnosed as gastric cancer in our hospital. She had multiple metastases of lungs, lymph nodes, bilateral ovaries, and uterus. After she underwent sub-total gastrectomy, bilateral oophorectomy, and total hysterectomy, she received adjuvant chemotherapy followed by docetaxel and S-1. After 6 courses of chemotherapy, PET/CT revealed no recurrences (complete response), and she was therefore administered S-1 for only 6 months. She has remained without recurrence 15 months after the operation.