Experience of weekly paclitaxel combined with orally administered doxifluridine therapy for advanced and recurrent gastric cancer-preliminary study

We designed a new regimen to evaluate the efficacy and feasibility of weekly paclitaxel combined with orally administered 5'-DFUR therapy against advanced and recurrent gastric cancer. Nine patients were enrolled. Weekly paclitaxel administration (PTX 60 mg/m2, 2 consecutive weeks, 1-week break) and oral administration of 5'-DFUR (460 mg/m2, 14 consecutive days) were performed on an ambulatory basis. This was repeated every 3 weeks until disease progression and/or severe toxic events occurred. The overall response rate was 44.4% with 22.2% complete response and 22.2% partial response in addition to 44.4% no changes beyond 3 months. In NC criteria, 3 patients showed clinical improvements, such as decreasing tumor markers, releasing from the ileus, and improvement of liver dysfunction. These results suggested that clinical benefits in 89% of patients. On the other hand, toxic events were restricted to grade 3 with 11.1% general fatigue and 11.1% appetite loss. Therefore, the weekly administration of PTX in conjunction with daily oral administration of 5'-DFUR therapy seems to be extremely useful, with excellent anti-tumor effect and tolerable adverse reactions for the treatment of recurrent gastric cancer on an ambulatory basis.     

A case of advanced gastric cancer with malignant ascites responding to weekly paclitaxel therapy

A 54-year-old woman with scirrhous gastric cancer in the upper third area was admitted to our hospital. She was diagnosed with advanced gastric cancer that was inoperable due to peritoneal metastasis, so weekly paclitaxel (PTX) therapy was carried out. After 2 courses, malignant ascites completely disappeared and bilateral hydronephrosis improved. After 4 courses, no ascites or hydronephrosis were seen. Only neutropenia (grade 2) and alopecia (grade 1) were observed as adverse events during the therapy, but no major adverse events were noted. We also investigated the concentration of paclitaxel in ascites. Two hours after intravenous injection of PTX, the concentration of PTX in ascites rose over the reported cytotoxic dose of PTX, and this available concentration was maintained after 48 hours. Weekly paclitaxel therapy is suggested to be one of the safe and useful treatments for advanced gastric cancer with malignant ascites.     

A case of advanced gastric cancer successfully treated with neoadjuvant chemotherapy of combined weekly paclitaxel and doxifluridine (5'-DFUR)

We report a case of advanced gastric cancer with metastasis to the paraaortic lymph nodes that showed a remarkable response to treatment with a combination of weekly paclitaxel and doxifluridine (5'-DFUR). The patient was a 72-year-old man. Oral chemotherapy of TS-1 was discontinued due to drug induced eruption. Alternatively, we administered weekly paclitaxel/5'-DFUR combination therapy. Paclitaxel was infused at a dose of 100-130 mg after short premedication and continued for 2-3 weeks with a 1 week rest. 5'-DFUR was administered orally at a dose of 800 mg/day for 14-21 consecutive days. After 4 courses of this therapy, the primary carcinoma and lymph nodes decreased in size (PR). Consequently, the patient underwent a total gastrectomy with paraaortic lymph node dissection, which resulted in a curative resection of the cancer cells macroscopically. Except for afebrile neutropenia (grade 4), no major adverse reactions were observed. Histological examination revealed that the cancer cells were degenerated to a moderate extent. Weekly paclitaxel/5'-DFUR combination may be a promising regimen for patients with advanced gastric cancer as preoperative chemotherapy.     

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.     

Evaluation of weekly paclitaxel and doxifluridine (5'-DFUR) combination therapy in patients with advanced or recurrent breast cancer

To evaluate the feasibility and efficacy of weekly paclitaxel and 5'-DFUR combination therapy in advanced or recurrent breast cancer, 13 patients were enrolled in this pilot study. 5'-DFUR was administered orally at a dose of 800 mg/day for 14 consecutive days, and paclitaxel was administered by 1 hour infusion at a dose of 80 mg/m2 after short premedication on day 1 and 8. This was repeated every 3 weeks, until disease progression or severe side effects precluded further treatment. Antiemetic agents and G-CSF were also administered, as needed. Nine patients had not received prior therapy, and four patients had received prior anthracycline containing therapy, two of whom were concomitantly receiving docetaxel treatment. Median administration time was 14 weeks, and median time to progression was 16.6 weeks. The overall response rate was 46.2% with 7.7% complete response and 38.5% partial response, and the response rate was consistent regardless of metastatic sites. Two patients achieved stable disease for at least 6 months and the clinical benefit was 61.5%. Responses were observed in 25% of the patients with prior anthracycline therapy. Grade 3/4 side effects involved leukopenia in 15.4%, peripheral neuropathy in 7.7%, malaise in 23.1% and nausea in 7.7%. There were no complaints of severe diarrhea. Although one patient withdrew from this study because of a hypersensitive reaction, this regimen was generally well tolerated and QOL was high enough so that it was possible to continue the regimen. Weekly paclitaxel and 5'-DFUR combination therapy seems to be feasible and effective in patients with advanced or recurrent breast cancer.     

A phase I study of doxifluridine combined with weekly paclitaxel for metastatic gastric cancer

Purpose Based on the synergistic effect in preclinical studies, a phase I clinical trial for the combination of paclitaxel and doxifluridine (an intermetabolite of capecitabine) was performed to determine the recommended dose for the treatment of patients with metastatic gastric cancer.Methods The dose of paclitaxel was increased from 60 mg/m² at level 1 to 90 mg/m² at level 5. It was administered as a 1-h infusion on days 1 and 8. The dose of doxifluridine was fixed at 600 mg/m² per day up to level 3, and escalated to 800 mg/m² per day at levels 4 and 5. It was administered orally for 2 weeks. The treatment was repeated every 3 weeks.Results A total of 28 patients were enrolled. No dose-limiting toxicity (DLT) was observed at levels 1 and 2 (paclitaxel 70 mg/m²). A DLT of grade 4 neutropenia lasting for more than 4 days was observed in one patient at level 3 (paclitaxel 80 mg/m²). In addition, the first five of six patients in this group experienced grade 3 neutropenia during the first treatment cycle. A further six patients were added in order to confirm the safety of this dosage level, and no more DLTs except for grade 3 nausea in one patient were observed in the second cohort. No DLT was seen in three patients at level 4 (paclitaxel 80 mg/m²). DLTs (grade 3 neuropathy in one patient and a treatment delay of the second cycle for more than 1 week due to grade 3 neutropenia in another) were observed in two out of six patients at level 5 (paclitaxel 90 mg/m²), and this dose level was determined as the maximum tolerated dose. The tumor response rate was 42% (95% confidence interval 20–67%) in 19 patients with measurable lesions.Conclusions The recommended dose was determined as 80 mg/m² of paclitaxel (days 1 and 8) and 800 mg/m² of doxifluridine (days 1–14) every 3 weeks. The results of this phase I study are encouraging and a phase II trial is thus warranted.     

A phase I study of combination chemotherapy using TS-1 and weekly paclitaxel for advanced gastric cancer

The safety of chemotherapy combining TS-1 and weekly paclitaxel for the treatment of unresectable and recurrent gastric cancer was evaluated in this study. Paclitaxel was administered by intravenous drip infusion at a starting dose (level 1) of 50 mg/m2 on days 1, 8, and 15. TS-1 was administered orally at a dose of 40 mg/m2twice a day for 2 weeks (days 1-14) followed by 2 weeks rest. A total of 9 patients were enrolled in this study. Two out of 6 patients treated with level 1 suffered from leukocytopenia and neutropenia, which were determined as dose-limiting toxicity (DLT). Three patients were treated with level 2, in which the dose of paclitaxel was increased up to 60 mg/m2. One of 3 patients suffered from grade 3 diarrhea and one patient from grade 4 leukocytopenia, eutrocytopenia, anemia, and stomatitis, which were determined as DLT. According to these results,level 1 of this regimen was recommended as a safe treatment for gastric cancer patients. A phase II study will be performed to evaluate the efficacy of the combination chemotherapy.     

A case of advanced gastric cancer treated with weekly paclitaxel with measurement of paclitaxel concentrations in blood and ascites

We measured paclitaxel (PTX) concentrations in blood and ascites in a patient with advanced gastric cancer treated with weekly paclitaxel (80 mg/m2). After 180 minutes from infusion of PTX, the concentration of PTX in ascites was 13 ng/ml, which was more than the reported cytotoxic dose of PTX (8.5 ng/ml). The concentration of PTX in ascites was retained, and rose rather slowly during a 24-hour period. The patient died soon after the measurement, meaning this measurement was taken at a time when the antitumor effect was ineffective and under poor general conditions. The result suggested, however, that the desired concentration of PTX in ascites can be obtained with a smaller dose of PTX in a regimen of weekly PTX.     

A case of recurrent gastric cancer effectively treated by combination chemotherapy of weekly paclitaxel and 5'- DFUR after showing resistance to weekly paclitaxel

The patient was a 35-year-old woman with lung, bone and lymphnode metastases of gastric cancer after a total gastrectomy two years earlier. For the first-line treatment, we performed TS-1+CDDP therapy but it showed no effect. Then, weekly paclitaxel was administered as second-line, but again without effect. Therefore, combination chemotherapy of weekly paclitaxel and 5'-DFUR was performed as third-line therapy. 5'-DFUR was given orally at a dose of 600 mg/day for consecutive daily administration, and paclitaxel was administered at a dose of 70 mg/m(2) on day 1, 8 and 15. This regimen was repeated every 4 weeks. No serious adverse reaction was observed. The condition of the patient had improved after 1 course, making it possible to conduct treatment on an ambulatory basis in the 2 courses and subsequent cycles. After 3 courses, the size of the lung metastasis was remarkably decreased. This case suggests that combination chemotherapy of weekly paclitaxel and 5'-DFUR might be a promising regimen for recurrent gastric cancer even for patients who show no effect with only paclitaxel administration.     

Combined chemotherapy with weekly Paclitaxel and doxifluridine for advanced and recurrent gastric cancers

We conducted combined therapy of weekly paclitaxel and doxifluridine (5'-DFUR) for 23 cases of advanced and recurrent gastric carcinomas to investigate their efficacy and safety. Subjects included 7 unresectable cases, 5 noncurative resection cases, and 11 recurrent cases. Twenty of the 23 subjects had a history of prior treatment with another anticancer drug. The treatment regime consisted of one course comprising 70 mg/m(2)of paclitaxel weekly for three consecutive weeks followed by one week rest, combined with 800 mg/day of 5'-DFUR orally. Results revealed a response rate of 17.6% (3/17), with 2 cases of CR, 1 case of PR, 10 cases of NC, and 4 cases of PD. One of the CR cases was an unresectable case involving a primary tumor, liver metastasis, and abdominal lymph node metastasis, while the other was a recurrent case involving abdominal lymph node metastasis. The median survival period was 387 days. The one-and two-year survival rates were 52% and 24%, respectively. In terms of adverse effects, there were only single cases of grade 3 leukopenia and grade 3 neutropenia, with no cases of grade 4 hemotoxicity. Both patients could be treated as outpatients. Combination therapy of weekly paclitaxel and 5'-DFUR can be an effective and safe therapy for advanced and recurrent gastric carcinomas.     

A case of advanced gastric cancer effectively treated with combination of weekly paclitaxel and hepatic arterial infusion of 5-FU/LV

The patient was a 66-year-old woman who underwent upper gastrointestinal endoscopy as part of a detailed examination because of loss of appetite and anemia, and type 2 gastric cancer was detected on the greater curvature in the pyloric area. Abdominal ultrasonography and CT revealed lymph node enlargement around the pyloric area and multiple liver metastases in both lobes of the liver. Curative resection was judged to be impossible, and oral S-1 therapy was started. However, no efficacy was observed even after the completion of three courses, and especially because of the rapid increase in the size of the liver metastases, treatment was switched to combination therapy consisting of a continuous hepatic artery infusion of 5-FU+Leucovorin (day 1-7) and weekly PTX for 3 consecutive weeks (day 8, 15, 22) followed by a 1-week rest. The tumor marker levels decreased rapidly, and at the end of 4 courses marked regression of the primary tumor and lymph node metastases as well as of the metastatic foci in the liver was observed. Adverse events have been mild, and at present, 6 months after the switch in treatment, good QOL has been maintained, and treatment is continuing. This method appears to be an effective treatment strategy for unresectable advanced gastric cancer complicated by liver metastasis.     

A case of recurrent gastric cancer with peritoneal dissemination responding to doxifluridine/paclitaxel combination chemotherapy as third-line treatment

A 50-year-old man had undergone total gastrectomy and splenectomy for advanced gastric cancer in October 2000, and was then treated with postoperative adjuvant chemotherapy for 2 years. In June 2005, we made a diagnosis of recurrent gastric cancer with peritoneal dissemination. Although the chemotherapy with TS-1/CPT-11 was started, it was discontinued after 2 courses because of subileus. Despite a change to second-line chemotherapy with CPT-11/CDDP, progressive disease due to a large amount of ascites was confirmed after 3 courses. Therefore, chemotherapy with doxifluridine (5'-DFUR)/paclitaxel (PTX) was selected as third-line treatment. After completion of 3 courses, abdominal computed tomography revealed a marked decrease of ascites. After 8 courses we discontinued 5'-DFUR/PTX chemotherapy, so the increase of ascites was remarkable. All response time was 197 days. The patient had good quality of life. 5'-DFUR/PTX combination chemotherapy can be expected to improve patient quality of life and show good therapeutic efficacy against recurrent gastric cancer with peritoneal dissemination.     

A case of gastric cancer with abdominal wall invasion treated by weekly low-dose paclitaxel therapy

Here we report a case of gastric cancer with diffuse abdominal wall invasion treated with weekly low-dose paclitaxel therapy. A 62-year-old male visited our hospital because of abdominal distention, prepubic tumor,and testicular hydrocele. Computed tomography revealed diffuse swelling of the abdominal wall and hydronephrosis of the right kidney. Upper gastrointestinal endoscopy demonstrated type 3' advanced gastric cancer. Pathological diagnosis of both gastric tumor and abdominal wall biopsy specimens was poorly-differentiated adenocarcinoma containing signet ring cell carcinoma. Low-dose paclitaxel (90 mg/body) was given once a week for 3 weeks. Abdominal wall swelling like cuirass disappeared after 2 courses of low-dose paclitaxel therapy. Nine repeated courses of this regimen have been given until now; the relapse of the abdominal wall invasion has not become apparent, and primary gastric lesion has been a stable disease. Diffuse abdominal wall invasion of gastric cancer like cuirass without ascites is a rare condition, and low-dose paclitaxel was very effective for this condition.     

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 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 metastatic gastric cancer responding to weekly administration of paclitaxel as a second-line therapy

We report a 65-year-old man who underwent distal gastrectomy for advanced and metastatic gastric cancer in June 2000. TS-1 was administered for remnant metastatic lesions as first-line chemotherapy, but a recurrence was found in June 2001. Paclitaxel 80 mg/m2 was then administered weekly in a 1-h infusion on day 1, 8, and 15 as one cycle. After two cycles of paclitaxel administration, the patient was relieved from abdominal pain, and a barium enema revealed marked improvement of the colonic stenosis due to the peritoneal metastasis. There have been few effective chemotherapeutic agents against peritoneal metastasis from gastric cancer to date; however, a weekly paclitaxel regimen is considered to be one of the promising regimens for metastatic and recurrent gastric cancer.     

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.     

紫杉醇联合FUDR治疗晚期胃癌的临床观察

为了观察紫杉醇(PTX)联合脱氧氟尿苷(FUDR)/亚叶酸钙(CF)方案治疗晚期胃癌近期疗效及其不良反应,将58例晚期胃癌患者,采用PTX135mg/m2,静脉滴入3h,d1,CF100mg/m2,静脉滴入2h,d1～d5,FUDR425mg/m2,静脉滴入2h,d1,再续滴入FUDR350mg/(m2.d),微量化疗泵24h持续滴入(civ)d1～d5,21d为1个周期,至少完成2个周期。58例晚期胃癌患者,CR3例(5.2%),PR30例(51.7%),SD13例(22.4%),PD12例(20.7%),总有效率(CR PR)达56.9%。主要不良反应为骨髓抑制、脱发和肌肉酸痛,无化疗相关死亡。初步研究结果提示,PTX联合FUDR/CF方案一线治疗晚期胃癌具有较好的疗效和安全性。