Randomized phase II study of daily and alternate-day administration of S-1 for advanced gastric cancer (JFMC43-1003).

Purpose: Although S-1 based chemotherapy for patients with advanced gastric cancer has generally been accepted in Japan, discontinuations of treatment have been reported due to grade 3 or more adverse events. The present randomized phase II study was conducted to test whether alternate-day administration of S-1 would be comparably efficient and reduce adverse events compared with conventional daily administration in the first-line chemotherapy for advanced gastric cancer.

Methods: 132 patients with advanced gastric cancer were randomly assigned to 1:2 ratios to receive treatment with daily at a standard dose of 80 mg/m/day or alternate-day administration group received S-1 on 4 days a week.

Efficacy of a continuous venous infusion of fluorouracil and daily divided dose cisplatin as adjuvant therapy in resectable colorectal cancer: a prospective randomized trial.

Purpose: Daily divided dose cisplatin (DDD-P) is used as an efficient modulator of fluorouracil (5-FU), as is leucovorin (LV). We performed a randomized trial to compare the efficacy 5-FU plus DDD-P (DDD-FP) therapy with 5-FU alone in resected colorectal cancer as the adjuvant therapy.

Methods: One hundred and eighty-eight stage II or III colorectal cancer patients were enrolled.

[The fourth report from Sapporo Tsukisamu Hospital - chemotherapy and its regimen as second choice for patients with early gastric cancer].

Surgical treatments for early gastric cancer, such as endoscopic procedures, are currently performed as standard therapy. However, when surgery is not possible due to physical or mental conditions, effective chemotherapy with minimum side effects is a second choice, although a suitable regimen has yet to be recommended. We thus retrospectively evaluated the Int FP regimen for 10 early gastric cancer patients.

[The third report from Sapporo Tsukisamu Hospital--chemotherapy for patients with advanced gastric cancer (peritoneal dissemination, peritonitis carcinomatosa)].

Recently, it became possible to reduce the size of tumors in patients with advanced or relapsed gastric cancer by chemotherapy with the combination of several kinds of anti-cancer drugs which are all effective and allowed for use with gastric cancer patients. However, chemotherapy alone can not cure patients with advanced gastric cancer that was shown to improve median survival time (MST), compared with patients provided with the best supportive care (BSC). According to reports from Europe, US and Japan,the MST of patients with advanced gastric cancer and those with peritoneal expansion treated by chemotherapy is almost 7-12 months and 5-6 months,respectively, both of which are short and unsatisfactory.

[The second report from Sapporo Tsukisamu hospital--chemotherapy for patients with advanced colorectal cancer].

The remedy,especially recent chemotherapy,against colorectal cancer is improving median survival time (MST) of patients with Stage IV advanced colorectal cancer. According to other reports,however,it seems to be difficult to improve it longer than 20 months. In May 2002, we devised a new regimen by intermittent dosage of 5-FU (-->S-1), CDDP and paclitaxel utilizing the difference of cell cycle between normal and cancer cells, and thirteen patients with advanced colorectal cancer (Stage IV) were treated with this regimen.

[The first report from Sapporo Tsukisamu Hospital--chemotherapy and chemoradiotherapy for patients with advanced pancreatic cancer].

The remedy, especially chemotherapy, for advanced pancreatic cancer is hardly ever successful in terms of efficacy rate and survival period, because it is virtually unable to contribute to the improvement of median survival time (MST). Thus,we devised a new intermittent dosage regimen utilizing the cell cycle difference of normal GI tract, bone marrow cell and pancreatic cancer cell, making use of 5-FU (-->S-1), CDDP and paclitaxel in March 2002. Ten patients with advanced pancreatic cancer (4 in Stage IVa and 6 in Stage IVb) were treated with this new regimen.

[Long-term repeatable chemotherapy for patients with advanced pancreatic cancer].

At present, the advanced pancreatic cancer is known to be one of the most resistant malignancies on chemotherapy. To improve the efficacy of chemotherapy, we shifted the aim of chemotherapy from a tumor regression to long-term survival, and sought for a repeatable regimen with little toxicity. Some of the novel (repeatable) regimens used a combination of 5-FU/S-1, CDDP and paclitaxel performed for 10 patients with advanced pancreatic cancer (4 cases of Stage IVa and 6 cases of Stage IVb).

[Pharmacokinetics of S-1].

S-1 is an attractive oral fluorouracil antitumor drug, which is being called "a self-rescuing drug". This novel oral fluoropyrimidine is combined with three pharmacological agents: tegafur (FT) which is a prodrug of 5-fluorouracil (5-FU), 5-chloro-2,4-dihydroxypyridine (CDHP) which inhibits dihydropyrimidine dehydrogenase (DPD) activity, and potassium oxonate (Oxo) which reduces gastrointestinal toxicity. Phase I and an early phase II clinical trials were performed about ten years ago, and these results had already been introduced to the Journal "Clinical Cancer Research Vol.

Combination phase I trial of a novel oral fluorouracil derivative S-1 with low-dose cisplatin for unresectable and recurrent gastric cancer (JFMC27-9902).

Purpose: The Japanese Foundation for Multidisciplinary Treatment of Cancer conducted a Phase I study of a novel oral fluorouracil derivative, S-1, combined with a low dose of cisplatin in unresectable and recurrent gastric cancer.

Experimental Design: S-1 was administered orally at 80-120 mg/body/day, depending on body surface area. One course consisted of consecutive administration for 28 days followed by a rest of 14 days.