Phase I/II trial of combination therapy with S-1 and weekly paclitaxel in patients with unresectable or recurrent gastric cancer.

PURPOSE: We aimed to examine the safety and antitumor effects of a combination of S-1 and paclitaxel in patients with unresectable or recurrent gastric cancer in a phase I/II setting. PATIENTS AND METHODS: The study was designed as a phase I/II clinical trial. In phase I portion, the dose of paclitaxel was escalated to estimate the maximum-tolerated dose (MTD) and recommended dose (RD) of paclitaxel with fixed dose of S-1. S-1 (daily dose, 80 mg/m(2)) was given orally on days 1-21 every 35-day cycle (rest on days 22-35). Paclitaxel was administered intravenously on days 1, 8 and 15, at an initial dose of 40 mg/m(2), stepping up to 70 mg/m(2) in 10-mg/m(2) increment. Dose-limiting toxicity (DLT) was defined as grade 4 hematological toxicity, grade 3 or higher nonhematological toxicity, and treatment discontinuation due to adverse reactions during the first course of treatment. In phase II portion, the efficacy and toxicity at the RD of paclitaxel with S-1 were assessed. RESULTS: The MTD of paclitaxel was estimated to be 60 mg/m(2), because >33.3% of patients (2/3) developed DLTs. DLT included postponement of treatment due to grade 2 neutropenia, and grade 3 stomatitis, anorexia, and nausea. Therefore, the RD of paclitaxel was estimated to be 50 mg/m(2). In the phase II portion, 22 patients were evaluated with 50 mg/m(2) paclitaxel and 80 mg/m(2) S-1 in a 35-day cycle. The response rate was 54.5% (95% CI, 32.2-75.6%). The median survival time was 283 days (95% CI, 218-508 days). The median number of treatment courses was 4 (range 1-10), indicating that this regimen could be given repeatedly. CONCLUSIONS: This phase I/II trial of combination therapy with S-1 and paclitaxel in patients with unresectable or recurrent gastric cancer showed that this regimen has substantial antitumor activity and can be given safely.

Liver perfusion chemotherapy with 5-Fluorouracil followed by systemic gemcitabine administration for resected pancreatic cancer: preliminary results of a prospective phase 2 study.

OBJECTIVES: Liver perfusion chemotherapy (LPC) for pancreatic cancer has been rarely undertaken in a postoperative adjuvant setting. We evaluated the feasibility and antitumor efficacy of LPC with 5-fluorouracil (5-FU) followed by gemcitabine treatment. METHODS: This prospective study enrolled 27 patients who underwent pancreatic resection and subsequent LPC + gemcitabine treatment during a 3-year period. The liver was infused with 5-FU (125 mg/body per day per route) via both routes of hepatic artery and portal vein for more than 21 days. After that, gemcitabine (1000 mg/m) was administered biweekly. RESULTS: Portal vein thrombosis developed in 1 patient, but 89% patients tolerated LPC for more than 21 days with no life-threatening complication. Systemic administration of gemcitabine was accomplished in 93%; however, 1 patient died of serious capillary leak syndrome. No grade 4 toxicity was recorded, except for that patient. Median survival time and disease-free survival were 27.5 and 24.5 months, respectively. Hepatic relapse was observed in 25.9% (n = 7). Survival was in favor of paraaortic node-negative cases (n = 20) with a 2-year survival of 68.7%. CONCLUSIONS: Liver perfusion chemotherapy was feasible with acceptable toxicity. Systemic use of gemcitabine also seems to be safe for the most part. This adjuvant chemotherapy shows promising survival benefit and seems to be indicative to paraaortic node-negative tumors.

[A case of rectal cancer with multiple liver and peritoneal metastases that responded dramatically to low-dose 5-FU plus LV and CDDP combination chemotherapy].

We have experienced successful treatment of a multiple hepatic metastasis of rectal cancer with combination chemotherapy. The patient is a 57-year-old male with bowel obstruction accompanied by rectal cancer (SE, N3, P1, H3, M (-) stage IV) who underwent a Hartmann operation with D3 lymph node dissection on July 6, 2000. The histopathological findings revealed a well-differentiated adenocarcinoma (se, INFbeta, n3, ly2, v2, p1). From the 11th postoperative day, combination chemotherapy using 5-FU 750 mg/day and LV 300 mg/day was performed once a week. When he underwent 5 combination chemotherapy treatments, adverse effects of grade 3 occurred, and the serum CEA level rose rapidly. We changed his regimen at that time. He underwent 2 courses of combination chemotherapy with 5-FU 500 mg/day and CDDP 10 mg/day for 5 days. Additional courses of combination chemotherapy with 5-FU 500 mg/day, LV 25 mg/day and CDDP 10 mg/day were performed weekly in the outpatient department. The treatment was effective, and a complete response (CR) was noted 4 months after the chemotherapy. The same combination chemotherapy was performed biweekly for one year after CR. The patient has been receiving a subsequent single administration of UFT and has remained in remission for 3 years and 7 months after surgery.

[Role of postoperative adjuvant chemotherapy with gemcitabine for pancreatic cancer: feasibility and anti-tumor effect].

BACKGROUND: The feasibility and anti-tumor activity of gemcitabine in postoperative adjuvant chemotherapy were evaluated retrospectively. PATIENTS AND METHODS: Sixteen patients with advanced pancreatic cancer, who had a pancreatic resection with curative intent over the three years up to February 2003, were enrolled in this study. Aggressive surgery with dissection of para-aortic nodes and nerves around the superior mesenteric and celiac artery was carried out. After the operation, all patients have been given biweekly administration of 1,000 mg/m2 gemcitabine for more than 12 courses. RESULTS: The chemotherapy was well tolerated with only mild symptomatic and hematologic toxicities. Grade 3 adverse effects were observed in only 3 patients (19%); nausea and vomiting in 1 patient and leucocytopenia in 2 patients. The disease-specific cumulative survival rates were 81% at 1 year and 47% at 2 years, with a median survival of 20.4 months. The median disease-free interval was 16.8 months in all patients. CONCLUSIONS: Adjuvant systemic chemotherapy utilizing gemcitabine was feasible with acceptable adverse effects. Gemcitabine is a promising agent for the treatment of resectable advanced pancreatic cancer, and a randomized control trial is warranted for gemcitabine-based chemotherapy.