s-1-(combination) and Anorexia

The S-1 +biweekly docetaxel (DOC) combination therapy was evaluated for advanced or recurrent gastric cancer patients. This combination therapy was evaluated in vitro using the nude rat-gastric cancer xenograft system. S-1 alone or DOC alone showed antitumor activity, and the antitumor activity was synergistic when two drugs were combined. In clinical settings, the schedule was S-1 80 mg/m2 (day 1-14, orally) and DOC (day 1 and day 15, intravenously) followed by a 2-week rest. In phase I study, the dose of DOC was evaluated, and a recommended dose for phase II was determined as 35 mg/m2. The entry for phase II study was completed, and the preliminary results of 33 patients showed the response rate of 21.2%. The incidence of more than grade 3 adverse effects was 29%(neutropenia, leukocytopenia, anorexia and mucositis). The S-1 +biweekly DOC combination therapy can be a candidate for outpatient chemotherapy for advanced or recurrent gastric cancer.

Topics: Animals; Anorexia; Antineoplastic Combined Chemotherapy Protocols; Clinical Trials, Phase I as Topic; Clinical Trials, Phase II as Topic; Docetaxel; Drug Combinations; Humans; Leukopenia; Neoplasm Transplantation; Neutropenia; Oxonic Acid; Quality of Life; Randomized Controlled Trials as Topic; Rats; Rats, Nude; Stomach Neoplasms; Stomatitis; Taxoids; Tegafur

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.

Topics: Administration, Oral; Anemia; Anorexia; Antineoplastic Combined Chemotherapy Protocols; Clinical Trials, Phase I as Topic; Clinical Trials, Phase II as Topic; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Combinations; Humans; Infusions, Intravenous; Maximum Tolerated Dose; Oxonic Acid; Paclitaxel; Stomach Neoplasms; Tegafur

Chemotherapy for colorectal cancer is now improving rapidly due to new drugs like oxaliplatin and molecular targeting drugs. The key drug, however, is still 5-fluorouracil (5-FU). S-1 is an oral 5-FU anti-tumor drug that combines three pharmacological agents: tegafur, 5-chloro-2,4-dihydroxypyridine, which inhibits dihydropyrimidine dehydrogenase activity, and potassium oxonate, which reduces gastrointestinal toxicity. The results of the phase II study suggested that S-1 as a single agent was active against metastatic colorectal cancer: CR rate was 36-40% and MST was about one-year. Toxicity was all tolerable. Clinical trials of S-1 with oxaliplatin or CPT-11 combination chemotherapy are ongoing in Japan. S-1 with molecular targeting drugs will also be studied. Therefore, S-1 is expected to play an important part in chemotherapy for colorectal cancer.

Topics: Administration, Oral; Anorexia; Antimetabolites, Antineoplastic; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Clinical Trials, Phase II as Topic; Colorectal Neoplasms; Drug Administration Schedule; Drug Combinations; Fluorouracil; Humans; Irinotecan; Leukopenia; Neutropenia; Oxonic Acid; Survival Rate; Tegafur

A combination therapy of irinotecan hydrochloride (CPT-11) with continuous intravenous infusions of (infusional) 5-fluorouracil (5-FU) and Leucovorin (LV) is often used to treat advanced colorectal cancer. However, recent concerns on safety and convenience have prompted the development of new oral fluoropyrimidine derivatives which improved regimens. Yamada et al conducted a phase I study to assess the maximum tolerated dose and recommended dose of S-1 combined with CPT-11. The study recommended that 150 mg/m2 of CPT-11 be given on day 1 and 80 mg/m2 of S-1 daily on days 1 to 14 every 3 weeks. Recently, several phase I/II studies assessed the efficacy and safety of the combined therapy with S-1 and CPT-11 in patients with advanced colorectal cancer. Some of the studies which were ongoing assessed a tri-weekly schedule regimen. Our results showed that S-1 plus CPT-11 was very effective, with a response rate of 63% and PFS of 8 months. Toxicity was generally mild and manageable on an outpatient basis. The current evidence showed that a combination of S-1 and CPT-11 was more convenient and easier to administer than a combination of CPT-11 plus infusional 5-FU and LV. It will be essential to prove that the combination of S-1 plus CPT-11 can replace the combination of infusional 5-FU and LV plus CPT-11 without negatively affecting efficacy and toxicity.

Topics: Adult; Aged; Anorexia; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Clinical Trials, Phase I as Topic; Clinical Trials, Phase II as Topic; Colorectal Neoplasms; Drug Administration Schedule; Drug Combinations; Female; Humans; Irinotecan; Leukopenia; Male; Middle Aged; Neutropenia; Oxonic Acid; Remission Induction; Survival Rate; Tegafur

The combination with cisplatin (CDDP) and 5-FU is considered the first choice chemotherapy for squamous cell carcinoma of the head and neck (HNSCC). S-1, a modulation of tegafur developed in Japan, is an active agent for HNSCC. Some clinical phase I/II studies about the combination with CDDP and S-1 have been reported. The combination showed a good response rate of 67.6% for advanced and recurrent HNSCC in our clinical phase I/II study. The regimens of S-1 combined with carboplatin or nedaplatin have also been reported. Regimens containing S-1 appear to have been effective for HNSCC. Multi-institutional phase II studies with a large sample size are needed in the future. The compliance for patients is better than a 5-FU injection because S-1 is orally administrated. The adverse effect, especially for bone mallow toxicity, is equal or upgraded compared with a 5-FU injection. The efficacy and adverse effects of CDDP plus S-1 should be studied in carefully designed phase II/III trials. S-1 will be one of the key drugs for HNSCC in the future.

Topics: Adult; Aged; Anemia; Anorexia; Antineoplastic Combined Chemotherapy Protocols; Bone Marrow; Carcinoma, Squamous Cell; Cisplatin; Clinical Trials, Phase I as Topic; Clinical Trials, Phase II as Topic; Drug Administration Schedule; Drug Combinations; Female; Head and Neck Neoplasms; Humans; Male; Middle Aged; Neoplasm Staging; Neutropenia; Oxonic Acid; Tegafur; Thrombocytopenia

Most cases of head and neck squamous cell carcinoma (HNSCC) are in the advanced stages, resulting in a poor prognosis. To improve the poor outcome, adjuvant chemotherapy is indispensable for advanced cases with a high relapse risk after standard definitive treatments including surgery and/or radiotherapy. To define an adequate administration schedule in adjuvant chemotherapy with S-1, a controlled randomized study in multi-institutes was done. The results showed the 2-week administration followed by 1-week rest was superior to the 4-week administration followed by the 2-week rest in terms of safety and efficacy. In the present paper, some problems of adjuvant chemotherapy were discussed, and the protocol was described in terms of a multi-institutional controlled randomized comparison study of S-1 versus UFT in an adjuvant chemotherapy setting for locally advanced HNSCC.

Topics: Anorexia; Antimetabolites, Antineoplastic; Carcinoma, Squamous Cell; Chemotherapy, Adjuvant; Drug Administration Schedule; Drug Combinations; Head and Neck Neoplasms; Humans; Leukopenia; Multicenter Studies as Topic; Oxonic Acid; Randomized Controlled Trials as Topic; Survival Rate; Tegafur

S-1 is a newly developed oral anti-tumor agent, which contains 5-chloro-2, 4-dihydroxypyridine and potassium oxonate to strengthen biological activities of 5-fluorouracil. Response rate of S-1 for advanced non-small cell lung cancer was reported to be 12.5-22%. Response rate of combination chemotherapy with S-1 plus cisplatin (CDDP) was reported to be 47%, and the median survival time was 11 months. Adverse events of the combination chemotherapy were milder than other combination chemotherapy described before. Therefore, S-1 plus CDDP combination chemotherapy is a future candidate for phase III clinical study.

Topics: Administration, Oral; Anemia; Anorexia; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Non-Small-Cell Lung; Cisplatin; Drug Administration Schedule; Drug Combinations; Female; Humans; Lung Neoplasms; Male; Neutropenia; Oxonic Acid; Remission Induction; Tegafur

A new oral type of 5-fluorouracil (5-FU) derivative possessed of both potent antitumor activity and less gastrointestinal (GI) toxicity was investigated and developed in the form of a combination of tegafur (FT), a masked form of 5-FU, and its two peculiar biochemical modulators. One is 5-chloro-2,4-dihydroxypyridine (CDHP), a new potent inhibitor of 5-FU degradation in vivo, and another is potassium oxonate (Oxo), a characteristic inhibitor of 5-FU phosphorylation, which distributes much higher in GI tract after p.o. administration. 5-FU levels in blood of rats following administration of FT, were markedly elevated and persisted for a long-time by co-oral CDHP corresponding to over 0.4 molar ratio to FT, like the case in continuous infusion of 5-FU, which resulted in an augmentation of antitumor efficacy in Yoshida sarcoma-bearing rats, although severe GI toxicity simultaneously occurred. To reduce 5-FU-induced toxicities such as diarrhea and body weight loss and to maintain the augmented antitumor activity, 0.5 to 2 molar Oxo was orally given to rats with one molar FT plus 0.4 molar CDHP. As a result, both severe GI injury and body weight loss were markedly inhibited by coadministration of 0.5 to 1.0 molar Oxo while high antitumor efficacy (about 90% inhibition of tumor growth) was maintained. However, such almost complete antitumor effect was reduced to about 50% inhibition of tumor growth by over 2 molar Oxo combined with one molar FT plus 0.4 molar CDHP. Based on these results, a novel 5-FU derivative, named S-1, was composed of one molar FT, 0.4 molar CDHP and one molar Oxo. S-1 showed an antitumor activity over 3-fold stronger than UFT (one molar FT plus 4 molar uracil) against Yoshida sarcoma and Sato lung carcinoma in rats and human colon carcinoma (KM12C) xenografted in nude rats when its minimum toxic dose was administered. Co-oral Oxo also significantly reduced the incidence of diarrhea and stomatitis induced by administration of FT-CDHP in beagle dogs. These results suggest that high antitumor activity and less GI toxicity of S-1 was brought about by the elevation in blood and tumor tissues and by selective decrease of 5-fluoronucleotides, an active metabolite of 5-FU, in GI tract.

Topics: Animals; Anorexia; Antimetabolites, Antineoplastic; Diarrhea; Dogs; Drug Combinations; Female; Fluorouracil; Immunologic Factors; Male; Mice; Mice, Nude; Oxonic Acid; Pyridines; Rats; Sarcoma, Yoshida; Tegafur; Vomiting

This study aimed to evaluate the feasibility, safety, and efficacy of postoperative adjuvant chemotherapy with docetaxel/cisplatin/S-1 (DCS) following S-1 therapy in patients with stage III gastric cancer after curative gastrectomy.. Patients with stage III gastric cancer who underwent D2 gastrectomy were enrolled. Adjuvant chemotherapy was initiated within 8 weeks of gastrectomy. The first cycle of chemotherapy consisted of S-1 monotherapy (day 1-14), followed by a 7-day rest period. Cycles 2 and 3 consisted of the following: S-1 (day 1-14) administration, followed by a 14-day rest period, and an intravenous infusion of cisplatin and docetaxel on days 1 and 15. After two cycles, S-1 was administered for up to 1 year.. Thirty patients were enrolled between 2014 and 2017. Febrile neutropenia of grade 3 or higher was the most common hematological toxicity with 4 patients (13.3%). Other hematological toxicities of grade 3 or higher were as follows: neutropenia in 3 (10.0%), leukopenia in 3 (10.0%), and anemia in 2 (6.7%) patients. Most frequent non-hematological toxicity of grade 3 was anorexia (n = 4, 13.3%) and general fatigue (n = 3, 10.0%); no grade 4 non-hematological toxicities were observed. Twenty-five patients (83.3%) completed two cycles of DCS treatment and 18 (60.0%) completed subsequent S-1 treatment for 1 year. The relative dose intensity of docetaxel and cisplatin was 0.86 and that of S-1 was 0.88.. The DCS regimen can be acceptable as an adjuvant chemotherapy and offers an effective postoperative treatment option for stage III gastric cancer patients.. UMIN000012785 .. 08/01/2014.

Topics: Adenocarcinoma; Aged; Anemia; Anorexia; Antineoplastic Combined Chemotherapy Protocols; Chemotherapy-Induced Febrile Neutropenia; Chemotherapy, Adjuvant; Cisplatin; Docetaxel; Drug Administration Schedule; Drug Combinations; Fatigue; Feasibility Studies; Female; Humans; Leukopenia; Male; Middle Aged; Neutropenia; Oxonic Acid; Patient Compliance; Stomach Neoplasms; Tegafur

A phase II study of S-1 plus leucovorin (LV) given in a 4-week schedule (2 weeks' administration followed by 2 weeks' rest) for patients with untreated metastatic colorectal cancer (mCRC) showed that the combination was effective, but grade 3 toxicities (diarrhea, stomatitis and anorexia) occurred at a relatively high rate. In this phase II study, we evaluated the efficacy and safety of a 2-week schedule of S-1 plus LV. Patients with mCRC received oral S-1 (40-60 mg) and LV (25 mg) twice daily for 1 week, followed by 1 week's rest. Treatment was repeated until disease progression or unacceptable toxicity. The primary endpoint was response rate. The pharmacokinetics of S-1 and LV in Chinese patients were evaluated on day 1 of the first cycle. Seventy-three patients were enrolled in Japan and China. Of 71 eligible patients, the response rate was 53.5%, and the disease control rate was 83.1%. Median progression-free survival and median overall survival were 6.5 and 24.3 months, respectively. The incidences of grade 3 toxicities were diarrhea 8.3%, stomatitis 8.3%, anorexia 2.8% and neutropenia 9.7%. There were no treatment-related deaths. The pharmacokinetics profiles of S-1 plus LV in Chinese patients were similar to those in Japanese patients. This 2-week schedule of S-1 plus LV showed good efficacy and better tolerability than the 4-week schedule. This therapy will be the base regimen for mCRC to be added by other cytotoxic or molecular-targeted drugs. The optimized treatment schedule for S-1 plus LV was 1 week on and 1 week off.

Topics: Adult; Aged; Aged, 80 and over; Anorexia; Antineoplastic Combined Chemotherapy Protocols; China; Colorectal Neoplasms; Diarrhea; Drug Administration Schedule; Drug Combinations; Female; Humans; Japan; Leucovorin; Male; Middle Aged; Neoplasm Metastasis; Neutropenia; Oxonic Acid; Stomatitis; Survival Analysis; Tegafur; Treatment Outcome

To determine the recommended dose (RD) for full-dose S-1 and low-dose gemcitabine combined with radiotherapy in patients with non-metastatic advanced pancreatic cancer.. Adult patients with non-metastatic advanced pancreatic cancer (Union for International Cancer Control T stage 3 or 4) were eligible. The weekly intravenous gemcitabine (level 0-1: 200 mg/ml,level 2: 300 mg/m on Days 1, 8, 15, 22, 29, 36) dose was escalated starting from level 1 in a 3+3 design along with full dose twice-daily oral S-1 (level 0: 60 mg/m2/day, level 1-2: 80 mg/ml/day), and was administered on the same days as radiotherapy (1.8 Gy x 28 days).. Eight patients were included in this study. A dose-limiting toxicity (DLT) (grade 4 neutropenia) was observed in one of the first three patients in level 1, and three additional patients received the level 1 dose without any severe adverse events. DLTs (grade 3/4 neutropenia) were then observed in the first two patients given level 2 dose. Therefore, level 1 was designated as the RD. Common grade 3/4 toxicities included neutropenia (62.5%), anorexia (37.5%), and pneumonitis (12.5%).. The combination of S-1 and gemcitabine with concurrent radiotherapy is a feasible regimen at the level 1 dose.

Topics: Aged; Anorexia; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Pancreatic Ductal; Chemoradiotherapy; Deoxycytidine; Drug Combinations; Female; Gemcitabine; Humans; Male; Middle Aged; Neoplasm Staging; Neutropenia; Oxonic Acid; Pancreatic Neoplasms; Radiation Pneumonitis; Tegafur; Treatment Outcome

The prognosis for locally advanced gastric cancer is poor despite advances in adjuvant chemotherapy. We did the Stomach cancer Adjuvant Multi-Institutional group Trial (SAMIT) to assess the superiority of sequential treatment (paclitaxel then tegafur and uracil [UFT] or paclitaxel then S-1) compared with monotherapy (UFT or S-1) and also the non-inferiority of UFT compared with S-1.. We did this randomised phase 3 trial with a two-by-two factorial design at 230 hospitals in Japan. We enrolled patients aged 20-80 years with T4a or T4b gastric cancer, who had had D2 dissection and a ECOG performance score of 0-1. Patients were randomly assigned to one of four treatment groups with minimisation for tumour size, lymph node metastasis, and study site. Patients received UFT only (267 mg/m(2) per day), S-1 only (80 mg/m(2) per day) for 14 days, with a 7-day rest period or three courses of intermittent weekly paclitaxel (80 mg/m(2)) followed by either UFT, or S-1. Treatment lasted 48 weeks in monotherapy groups and 49 weeks in the sequential treatment groups. The primary endpoint was disease-free survival assessed by intention to treat. We assessed whether UFT was non-inferior to S-1 with a non-inferiority margin of 1·33. This trial was registered at UMIN Clinical Trials Registry, number C000000082.. We randomly assigned 1495 patients between Aug 3, 2004, and Sept 29, 2009. 374 patients were assigned to receive UFT alone, 374 to receive S-1 alone, 374 to received paclitaxel then UFT, and 373 to receive paclitaxel then S-1. We included 1433 patients in the primary analysis after at least 3 years of follow-up (359, 364, 355, and 355 in each group respectively). Protocol treatment was completed by 215 (60%) patients in the UFT group, 224 (62%) in the S-1 group, 242 (68%) in the paclitaxel then UFT group, and 250 (70%) in the paclitaxel then S-1 group. 3-year disease-free survival for monotherapy was 54·0% (95% CI 50·2-57·6) and that of sequential treatment was 57·2% (53·4-60·8; hazard ratio [HR] 0·92, 95% CI 0·80-1·07, p=0·273). 3-year disease-free survival for the UFT group was 53·0% (95% CI 49·2-56·6) and that of the S-1 group was 58·2% (54·4-61·8; HR 0·81, 95% CI 0·70-0·93, p=0·0048; pnon-inferiority=0·151). The most common grade 3-4 haematological adverse event was neutropenia (41 [11%] of 359 patients in the UFT group, 48 [13%] of 363 in the S-1 group, 46 [13%] of 355 in the paclitaxel then UFT group, and 83 [23%] of 356 in the paclitaxel then S-1 group). The most common grade 3-4 non-haematological adverse event was anorexia (21 [6%], 24 [7%], seven [2%], and 18 [5%], respectively).. Sequential treatment did not improve disease-free survival, and UFT was not non-inferior to S-1 (and S-1 was superior to UFT), therefore S-1 monotherapy should remain the standard treatment for locally advanced gastric cancer in Japan.. Epidemiological and Clinical Research Information Network.

Topics: Adenocarcinoma; Aged; Anorexia; Antineoplastic Combined Chemotherapy Protocols; Chemotherapy, Adjuvant; Disease-Free Survival; Drug Combinations; Female; Humans; Intention to Treat Analysis; Male; Middle Aged; Neoplasm Staging; Neutropenia; Oxonic Acid; Paclitaxel; Stomach Neoplasms; Survival Rate; Tegafur; Uracil

In our previous randomized controlled trial, the addition of S-1 to gemcitabine for advanced pancreatic cancer did not prolong overall survival (OS) significantly, despite its higher response rate and longer progression-free survival (PFS). Leucovorin is known to enhance efficacy of S-1, and we conducted this phase I trial of combination therapy of gemcitabine, S-1 and leucovorin (GSL).. Patients with advanced pancreatic cancer who had received no prior chemotherapy were eligible for this study. Gemcitabine was administered at an escalating dose of 600, 800 and 1,000 mg/m(2) over 30 min on day 1, and oral S-1 at a dose of 40 mg/m(2) twice daily and oral leucovorin at a dose of 25 mg twice daily on days 1-7, every 2 weeks. A standard "3 + 3" phase I dose escalation design was utilized.. Fifteen patients were enrolled across three dose levels. Three patients developed DLTs: two patients in level 1 (grade 3 anorexia in 1 and grade 3 anorexia, stomatitis and diarrhea in 1) and one patient in level 2 (grade 3 deep vein thrombosis). No DLT was observed in level 3. Response rate and the disease control rate were 33 and 93 %, respectively. The median PFS and OS were 5.4 and 16.6 months. Ten of 12 patients (83 %) with elevated CA19-9 at baseline had a ≥ 50 % decline.. RD of gemcitabine in GSL was determined as 1,000 mg/m(2). GSL was well tolerable and showed promising results in advanced pancreatic cancer.

Topics: Aged; Anorexia; Antineoplastic Combined Chemotherapy Protocols; Deoxycytidine; Diarrhea; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Combinations; Female; Gemcitabine; Humans; Leucovorin; Male; Middle Aged; Oxonic Acid; Pancreatic Neoplasms; Stomatitis; Survival Analysis; Tegafur; Treatment Outcome; Venous Thrombosis

This study aimed to compare the efficacy and toxicity of weekly paclitaxel plus S-1 with weekly paclitaxel plus 5-fluorouracil in treating advanced gastric cancer as first line regimen. The primary end-point was disease control rate (DCR).. Patients with advanced or recurrent gastric cancer were randomly assigned to an experimental arm or a control arm. The experimental arm's dosage schedule was paclitaxel 60 mg/m2 (intravenous infusion) on days 1, 8 and 15 and S-1 80-120 mg/d (oral administration) on days 1-14. Control arm patients were given the same paclitaxel, combined with 5-fluorouracil 500 mg/m2 (continuous intravenous infusion) on days 1-5; and leucovorin 20 mg/m2 (intravenous infusion) on days 1-5. All schedules were repeated every 28 d.. A total of 240 patients were enrolled and equally randomised into two arms. The overall response rate and DCR of the experimental arm was non-inferior to that of the control arm both in the per-protocol set and the full analysis set. The secondary end-point median progression-free survival (PFS) of the experimental and control arms was 153 and 129 d, with the hazard ratio of 0.641 (95% CI: 0.473-0.868, P = 0.004). The hazard ratio of the time to treatment failure of the two arms was 1.449 (95% CI: 0.705-2.980, P = 0.229). The six-month PFS rates of both arms were similar (31.3% versus 31.8%, P = 0.94). Cox regression analysis indicated that only treatment regimen and age were independent predictive factors for PFS. The most common adverse events were haematological and gastrointestinal. The rates of grade 3-4 adverse events were not significantly different between the two study arms and were mostly lower than 5%.. Weekly paclitaxel combined with S-1 is an active and well-tolerated regimen, supporting the view that S-1 can be an alternative for infusional 5-fluorouracil for advanced gastric cancer.

Topics: Administration, Oral; Adolescent; Adult; Aged; Anorexia; Antineoplastic Combined Chemotherapy Protocols; Drug Administration Schedule; Drug Combinations; Female; Fluorouracil; Humans; Infusions, Intravenous; Kaplan-Meier Estimate; Leucovorin; Leukopenia; Male; Middle Aged; Multivariate Analysis; Nausea; Oxonic Acid; Paclitaxel; Stomach Neoplasms; Tegafur; Treatment Outcome; Young Adult

This study investigated the maximum tolerated dose (MTD) of S-1 with concurrent radiotherapy in patients with head and neck cancer, based on the frequency of dose-limiting toxicities (DLT). S-1 was administered orally at escalating doses from 40 mg/m(2) b.i.d. on the days of delivering radiotherapy, which was given at a total dose of 64-70 Gy in 32-35 fractions over 6-7 weeks. A total of 12 patients (3 patients at 40 mg/m(2), 6 patients at 60 mg/m(2), and 3 patients at 80 mg/m(2)) were enrolled in this trial. At the dose of 80 mg/m(2), two of the three patients developed DLT (Grade 3 anorexia and rhabdomyolysis) due to S-1, so the MTD was determined to be 80 mg/m(2). Among the 12 enrolled patients, 9 (75%) showed a complete response and 3 (25%) showed a partial response. The overall response rate was 100%. The recommended dose of S-1 with concurrent radiotherapy is 60 mg/m(2).

Topics: Administration, Oral; Aged; Aged, 80 and over; Anorexia; Antimetabolites, Antineoplastic; Carcinoma, Squamous Cell; Combined Modality Therapy; Dose-Response Relationship, Drug; Drug Combinations; Female; Head and Neck Neoplasms; Humans; Male; Maximum Tolerated Dose; Middle Aged; Oxonic Acid; Rhabdomyolysis; Tegafur; Treatment Outcome

To establish a safe, long-term regimen of docetaxel (DOC) and cisplatin (CDDP) in an outpatient setting for gastric cancer refractory to S-1 adjuvant chemotherapy, a dose-escalating phase I study was conducted. Cohorts of patients were treated with escalating doses of DOC (starting at 20 mg/m² per week with 5 mg/m² increments) and a fixed dose of CDDP (25 mg/m²). Drugs were administered on days 1, 8, and 15. A cycle of this treatment was 28 days. In total, 52 courses were performed, and the mean number of courses was 5.3. Two of the four patients at dose level 3 showed dose-limiting toxicities (grade 4 neutropenia, and grade 3 anorexia and dehydration). The recommended dose (RD) of DOC was therefore defined as 25 mg/m². There is a need for a phase II clinical trial using this regimen in patients with S-1-refractory stage II/III gastric cancer.

Topics: Aged; Anorexia; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Chemotherapy, Adjuvant; Cisplatin; Cohort Studies; Dehydration; Docetaxel; Dose-Response Relationship, Drug; Drug Combinations; Drug Resistance, Neoplasm; Female; Follow-Up Studies; Humans; Male; Middle Aged; Neoplasm Staging; Neutropenia; Oxonic Acid; Stomach Neoplasms; Taxoids; Tegafur

S-1 is an oral fluoropyrimidine derivative that has demonstrated favorable antitumor activity in patients with metastatic pancreatic cancer. The aim of this study was to evaluate safety and efficacy of S-1 and concurrent radiotherapy in patients with unresectable locally advanced pancreatic cancer.. Patients with histopathologically proven, unresectable, locally advanced pancreatic cancer were eligible. Radiotherapy was delivered in 1.8 Gy daily fractions to a total dose of 50.4 Gy over 5.5 weeks. S-1 was administered orally twice a day at a dose of 80 mg/m(2)/day from day 1 to 14 and 22 to 35. Two weeks after the completion of chemoradiotherapy, maintenance chemotherapy with S-1 was administered for 28 days every 6 weeks until progression.. Thirty-four patients were enrolled in this study. The most common Grade 3 toxicities during chemoradiotherapy were anorexia (24%) and nausea (12%). The overall response rate was 41% (95% confidence interval, 25%-58%) and overall disease control rate (partial response plus stable disease) was 97%. More than 50% decrease in serum CA 19-9 was seen in 27 of 29 evaluable patients (93%). The median progression-free survival was 8.7 months. The median overall survival and 1-year survival rate were 16.8 months and 70.6%, respectively.. Oral S-1 and concurrent radiotherapy exerted a promising antitumor activity with acceptable toxicity in patients with locally advanced pancreatic cancer. This combination therapy seems to be an attractive alternative to conventional chemoradiotherapy using 5-fluorouracil infusion.

Topics: Adult; Aged; Anorexia; Antimetabolites, Antineoplastic; CA-19-9 Antigen; Combined Modality Therapy; Deoxycytidine; Disease Progression; Drug Administration Schedule; Drug Combinations; Female; Gemcitabine; Humans; Male; Middle Aged; Nausea; Oxonic Acid; Pancreatic Neoplasms; Prospective Studies; Radiotherapy Dosage; Tegafur

The aim of this multicenter Phase II study was to assess the efficacy and toxicity of gemcitabine and S-1 combination therapy for metastatic pancreatic cancer.. Chemotherapy-naïve patients with histologically or cytologically proven metastatic pancreatic adenocarcinoma were eligible for this study. Gemcitabine was administered at a dose of 1000 mg/m(2) over 30 min on days 1 and 8, and oral S-1 at a dose of 40 mg/m(2) twice daily from days 1 to 14, repeated every 3 weeks.. A total of 55 patients were included and the efficacy and toxicity were analyzed in 54 patients who received at least one dose of gemcitabine and S-1 combination therapy. Although no complete response was seen, a partial response was achieved in 24 patients, resulting in an overall response rate of 44.4% (95% confidence interval: 30.9-58.6%). The median progression-free survival was 5.9 months (95% confidence interval: 4.1-6.9 months) and the median overall survival was 10.1 months (95% confidence interval: 8.5-10.8 months) with a 1-year survival rate of 33.0%. The major Grade 3-4 toxicities were neutropenia (80%), leucopenia (59%), thrombocytopenia (22%), anorexia (17%) and rash (7%). Hematological toxicity was mostly transient and there was only one episode of febrile neutropenia ≥Grade 3.. Gemcitabine and S-1 combination therapy produced a high response rate with good survival in patients with metastatic pancreatic cancer. A randomized Phase III study to confirm the efficacy of gemcitabine and S-1 combination therapy is ongoing.

Topics: Adenocarcinoma; Adult; Aged; Anorexia; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Adenosquamous; Deoxycytidine; Disease-Free Survival; Drug Combinations; Drug Eruptions; Female; Gemcitabine; Humans; Kaplan-Meier Estimate; Leukopenia; Male; Middle Aged; Neoplasm Metastasis; Neutropenia; Oxonic Acid; Pancreatic Neoplasms; Tegafur; Thrombocytopenia; Treatment Outcome

This prospective multicenter phase II study was carried out to investigate the efficacy, safety and pharmacokinetics of S-1 monotherapy in elderly patients over 75 years of age, with unresectable advanced or recurrent gastric cancer.. Patients had measurable or evaluable lesions according to the Japanese Classification of Gastric Carcinoma. S-1 (25-60 mg determined by the body surface area and creatinine clearance) was given orally, twice daily. A course of treatment consisted of 4-week administration followed by a 2-week rest period, and the patients received repeated courses.. Thirty-three patients were enrolled. Pharmacokinetics of S-1 was studied in six patients, and the maximum plasma concentrations of respective metabolites after S-1 administration were found to be similar to those reported for younger cancer patients. The overall response rate in 33 patients was 21.2% (95% CI, 10.7-37.8%), and median progression-free survival was 3.9 months, with a median overall survival of 15.7 months. Frequently noted adverse events include leukopenia, neutropenia, anemia, anorexia, and fatigue. As for serious adverse events, relatively higher frequencies of anemia (9%) and anorexia (12%) of grade 3 severity were found, but there were no grade 4 episodes.. The results suggest that S-1 monotherapy is safe and useful for elderly patients with unresectable advanced or recurrent gastric cancer when the dose is selected with caution, taking into account renal function.

Topics: Aged; Aged, 80 and over; Anorexia; Antimetabolites, Antineoplastic; Drug Combinations; Fatigue; Female; Humans; Leukopenia; Male; Metabolic Clearance Rate; Neutropenia; Oxonic Acid; Prospective Studies; Stomach Neoplasms; Survival Analysis; Tegafur; Treatment Outcome

This study was conducted to evaluate the efficacy and safety of S-1, an oral fluoropyrimidine derivative, in Japanese patients with castration-resistant prostate cancer (CRPC). The primary endpoint was prostate-specific antigen (PSA) response.. In this open-label phase II study, S-1 was started at a dose of 80, 100 or 120 mg daily based on body surface area (BSA) for 28 days, followed by 14 days of rest. Patients with histological proof of prostate cancer refractory to hormonal therapies were eligible. Patients who received prior chemotherapy were excluded. All patients provided written informed consent. To observe 20% confirmed PSA response, 33 assessable patients were needed. Treatment was continued until disease progression or the development of intolerable toxicity.. A total of 35 eligible patients were enrolled. The median number of treatment cycles was 3. PSA response was observed in 8 patients (22.9%, 90% CI 11.9-37.5), including 3 in which (8.6%) the PSA level normalized. The median overall survival was 25.4 months. The most common treatment-related grade 3 toxicity was anorexia (14.3%). There was no death during the study.. S-1 monotherapy is active against castration-resistant prostate cancer and has acceptable toxicity.

Topics: Adult; Aged; Alanine Transaminase; Androgen Antagonists; Anorexia; Antimetabolites, Antineoplastic; Aspartate Aminotransferases; Bilirubin; Body Surface Area; Dose-Response Relationship, Drug; Drug Combinations; Drug Tolerance; Humans; Lymphatic Metastasis; Male; Middle Aged; Orchiectomy; Oxonic Acid; Prostate-Specific Antigen; Prostatic Neoplasms; Safety; Tegafur; Treatment Outcome

Although S-1 is effective against advanced gastric cancer (AGC), its efficacy in elderly patients has not yet been investigated sufficiently. We assessed the efficacy and safety of S-1 monotherapy in elderly patients with AGC.. We conducted a retrospective review of the data of 153 patients with unresectable/recurrent gastric adenocarcinoma who received S-1 monotherapy as first-line chemotherapy at our institution. S-1 was administered orally twice daily at the dose of 40 mg/m², on days 1-28, every 6 weeks. We categorized the patients into three groups, the young (≤65 years old), the middle-aged (66-75 years old), and the elderly (≥76 years old); and the drug toxicity, objective responses, progression-free survivals, and overall survivals were compared among the three groups.. The incidence of leukopenia of grade 3 or greater in the three groups was 7%, 5%, and 13%, and that of anemia was 9%, 18%, and 27%, respectively. In regard to nonhematological toxicities, the incidence of nausea of grade 3 or greater was 3%, 5%, and 13%; that of fatigue was 5%, 11%, and 20%; and that of anorexia was 5%, 6%, and 27%, respectively. As for the treatment efficacy, the objective response rates, median progressionfree survivals, and overall survivals in the young, middle-aged, and elderly groups were 53%, 46%, and 33%; 7.8, 5.6, and 3.9 months; and 16.9, 17.1; and 7.7 months, respectively.. Although S-1 monotherapy showed moderate efficacy in elderly (≥76 years) patients with AGC, patients in this age group showed higher incidences of severe toxicities than the younger patients.

Topics: Adenocarcinoma; Administration, Oral; Age Factors; Aged; Aged, 80 and over; Anemia; Anorexia; Antimetabolites, Antineoplastic; Chemotherapy, Adjuvant; Drug Administration Schedule; Drug Combinations; Fatigue; Female; Humans; Leukopenia; Male; Middle Aged; Nausea; Neoplasm Recurrence, Local; Oxonic Acid; Retrospective Studies; Stomach Neoplasms; Survival Analysis; Tegafur; Treatment Outcome

To define the maximum-tolerated dose (MTD) of S-1, given daily for 2 weeks followed by a 1-week rest, with a fixed dose of cisplatin on the initial day, and to determine the activity and safety of this regimen at the recommended dose (RD) when used as first line treatment of advanced gastric cancer (AGC).. Cisplatin was fixed at a dose of 60 mg/m2 on day 1 (D1) and the starting dose of S-1 was 60 mg/m2/day (30 mg/m2 bid) (level I) on D1 to D14, every 3 weeks. The dose of S-1 was increased by 5 mg/m2 bid up to 100 mg/m2/day (level V) unless the MTD was achieved.. Sixty-two eligible patients were enrolled. MTD was set at level V with two of three patients developing grade 3 diarrhea or febrile neutropenia. The RD was determined at level IV (90 mg/m2/day). After the first 20 patients were enrolled in phase II, the protocol was amended; the S-1 dose was reduced to 80 mg/m2/day (N=23) because of poor bone marrow recovery. The objective response was observed in 20 of 42 evaluable patients (48%). SD was achieved in 15 (36%). The median PFS was 5.3 months (95% CI, 4.6-6.0 months) with a median OS of 10.0 months (95% CI, 5.1-14.8 months). Grade 3-4 toxicities included neutropenia (33%), anemia (31%), and anorexia (24%).. The 3-week combination of cisplatin plus S-1 is active against AGC with favorable toxicitiy profiles. The phase II schedule or doses may need further refinements.

Topics: Adult; Aged; Anemia; Anorexia; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Diarrhea; Drug Administration Schedule; Drug Combinations; Female; Fever; Humans; Male; Maximum Tolerated Dose; Middle Aged; Neoplasm Metastasis; Neoplasm Recurrence, Local; Neutropenia; Oxonic Acid; Stomach Neoplasms; Tegafur

A pre-clinical study demonstrated that paclitaxel induced thymidine phosphorylase in the tumor tissues. The combination of paclitaxel and doxifluridine is expected to exert extra anti-tumor effects. We evaluated the efficacy of this combination in patients with unresectable or recurrent gastric cancer who had been previously treated with S-1.. Registration was started to enroll 35 patients with advanced/recurrent gastric cancer, who were selected among those with measurable lesions fitting to response evaluation criteria in solid tumors, and with resistant to S-1 treatment. This regimen is consisted of paclitaxel, 80 mg/m(2), iv on days 1 and 8; and doxifluridine, 600 mg/m(2), po on days 1-14. The treatment was repeated every three weeks. Primary endpoint was response rate (RR); and secondary endpoints were overall survival (OS), progression free survival (PFS) and onset rate of adverse events.. From September 2003 to March 2005, 35 patients were registered: including 28 men; 7 women; median age of 66 years (range, 49-75 years); and performance status (PS) levels were, zero with 21 and one with 14 patients. In 33 eligible patients, except two, clinical usefulness was evaluated resulting in RR of 18.2% (partial response, 6; stable disease, 15; progressive disease, 10; and not evaluable, 2 patients). Median survival time was 321 days and median PFS was 119 days. Severe adverse events were found in three patients to discontinue the present treatment.. The combination of paclitaxel and doxifluridine might be a treatment of choice as a second line chemotherapy for patient undergone S-1 treatment.

Topics: Adenocarcinoma; Aged; Anemia; Anorexia; Antineoplastic Combined Chemotherapy Protocols; Disease-Free Survival; Drug Combinations; Drug Resistance, Neoplasm; Female; Floxuridine; Humans; Liver Neoplasms; Lung Neoplasms; Lymphatic Metastasis; Male; Middle Aged; Neoplasm Recurrence, Local; Neutropenia; Oxonic Acid; Paclitaxel; Peritoneal Neoplasms; Stomach Neoplasms; Survival Rate; Tegafur; Thrombocytopenia

This Phase II study assessed the activity and safety of biweekly paclitaxel and oral S-1 as treatment for unresectable and recurrent gastric cancer. The maximum tolerated dose for this regimen had been established previously in a Phase I study performed in Japanese patients.. Chemotherapy was performed using two anticancer agents, S-1 and paclitaxel. Oral S-1 (80 mg/m(2)) was administered twice a day after meals for two consecutive weeks from Day 1 to 14, followed by a 2 week recovery period; paclitaxel (120 mg/m(2)) was administered intravenously, biweekly, on Days 1 and 15. The patient received cycles of this regimen every 4 weeks (q 28-day cycles). The primary end point was the response rate according to the Response Evaluation Criteria in Solid Tumors.. A total of 39 patients (median age, 65 years) were enrolled; 13 other patients were screened, but found to be ineligible. All patients had unresectable and recurrent gastric cancer. The most common treatment-related Grade 3/4 adverse events were neutropenia (37.5%), appetite loss, diarrhea, decreased sodium (each 5%), and anemia, increased alanine aminotransferase, general fatigue, and dizziness (each 2.5%). Almost all the patients experienced alopecia. Intent-to-treat analysis showed a response rate of 43.6%. With a median follow-up of 14 months (range 8-21 months), median survival was 256 days and the median time to progression was 4 months.. A combination regimen of biweekly paclitaxel and oral S-1 was well tolerated and showed promising activity against unresectable and recurrent gastric cancer.

Topics: Adenocarcinoma; Aged; Alopecia; Anorexia; Antineoplastic Combined Chemotherapy Protocols; Disease Progression; Disease-Free Survival; Drug Combinations; Female; Gastrointestinal Diseases; Humans; Hyponatremia; Kaplan-Meier Estimate; Male; Middle Aged; Neutropenia; Oxonic Acid; Paclitaxel; Stomach Neoplasms; Survival Analysis; Tegafur

A combination of irinotecan with continuous intravenous infusions of 5-fluorouracil (5-FU) and leucovorin (LV) is often used to treat advanced colorectal cancer. However, recent concerns about safety and convenience have prompted the development of new oral fluoropyrimidine derivatives and improved regimens. This phase II study evaluated the efficacy and safety of the oral fluoropyrimidine S-1 plus irinotecan in patients with previously untreated advanced or recurrent colorectal cancer.. Forty eligible patients with histologically confirmed colorectal adenocarcinoma received this treatment. S-1 was administered orally on days 1 to 14 of a 21-day cycle. Patients were assigned on the basis of body surface area (BSA) to receive one of the following oral doses twice daily: 40 mg (BSA < 1.25 m(2)), 50 mg (BSA > or = 1.25 to < 1.50 m(2)), or 60 mg (BSA > or = 1.50 m(2)). Irinotecan (150 mg/m(2)) was administered by intravenous infusion on day 1.. A total of 327 courses of treatment were administered to 40 patients. Five patients had complete responses, and 20 had partial responses. The overall response rate was 62.5% (95% confidential interval, 47.5%-77.5%). Median progression-free survival was 8.0 months (95% confidential interval, 5.2-11.4 months). The rates of grade 3 or 4 toxicity were as follows: neutropenia, 15%; anemia, 7.5%; anorexia, 12.5%; and diarrhea, 7.5%.. Combined treatment with S-1 and irinotecan is an effective, well tolerated, and convenient regimen in patients with advanced colorectal cancer. Our findings suggest that combined treatment with S-1 and irinotecan is a promising regimen, offering benefits in terms of safety and survival as compared with conventional regimens in patients with advanced colorectal cancer.

Topics: Adenocarcinoma; Adult; Aged; Anemia; Anorexia; Antimetabolites, Antineoplastic; Antineoplastic Agents, Phytogenic; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Colorectal Neoplasms; Diarrhea; Disease-Free Survival; Drug Combinations; Female; Humans; Irinotecan; Male; Middle Aged; Neoplasm Staging; Oxonic Acid; Survivors; Tegafur; Treatment Outcome

We developed a combination chemotherapy, comprising weekly dosing of iv cisplatin (days 1 and 8) combined with a fixed dose (70 mg/m2/day) of S-1 (days 1-14) for patients with metastatic gastric cancer. The treatment was repeated every 3 weeks. Twenty patients were studied. Dose-limiting toxicities of grade 3 diarrhea and stomatitis were observed in one patient at the dose of cisplatin 20 mg/m2. Grade 2 gastrointestinal adverse reactions, such as nausea and anorexia, were seen in approximately half of patients at this dose level within the first two treatment cycles. This was the maximum acceptable level. The overall response rate in 18 patients evaluated was 61%. The median survival was 11 months, despite including 11 pre-treated patients. S-1 given with weekly cisplatin was a feasible and promising combination regimen for an outpatient setting.

Topics: Administration, Oral; Adult; Aged; Anorexia; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Diarrhea; Drug Administration Schedule; Drug Combinations; Female; Humans; Infusions, Intravenous; Male; Maximum Tolerated Dose; Middle Aged; Oxonic Acid; Stomach Neoplasms; Stomatitis; Survival Rate; Tegafur

In the present article, we have summarized the phase I/II clinical trials on combination therapy of S-1 and docetaxel. With result of the phase I study, patients were treated with intravenous infusion of 40 mg/m2 docetaxel on day 1 and oral S-1 80 mg/m2/day on days 1 to 14 every 3 weeks. Forty eight patients received a total of 272 treatment cycles. No complete responses (CRs) and 27 partial responses (PRs) were observed for an overall response rate (CR+PR) of 56.2% (95% CI, 38-66%). Eighteen patients (37.5%) had stable disease (SD), and 3 patients (6.2%) had progressive disease (PD) as best response. The tumor control rate (CR+PR+SD) was 93.8% (95% CI, 83-98%). The median overall survival was 14.3 months (95% CI: 10.7-20.3 months) and the median time to tumor progression was 7.3 months (95% CI: 4.2-10.7 months). The most common grade 3-4 hematologic toxicities were neutropenia 58.3%, leukopenia 41.7%, febrile neutropenia 8.3%, and anemia 8.3%. The most common grade 3 nonhematologic toxicities were anorexia 14.6%, stomatitis 8.3%, nausea 6.3%, diarrhea 4.2%, constipation 4.2%, and vomiting 2.1%. No grade 4 nonhematologic toxicities were reported, and all treatment-related toxicities were resolved. The mechanisms underlying these synergistic effects of S-1 and docetaxel were examined by expression and activity analyses of 5-FU metabolic enzymes. The expressions of thymidylate synthase (TS) and dihydropyrimidine dehydrogenase (DPD) were decreased and that of orotate phosphorybosyl transferase (OPRT) was increased in mRNA, protein level and activity assay after the treatment with docetaxel and 5-FU in the TMK-1 gastric cancer cell. These findings strongly indicate that the combination chemotherapy of docetaxel and S-1 is effective against gastric carcinomas and therefore is a good candidate as a standard chemotherapeutic strategy in treating these tumors.

Topics: Adult; Aged; Anorexia; Antineoplastic Combined Chemotherapy Protocols; Docetaxel; Drug Administration Schedule; Drug Combinations; Humans; Infusions, Intravenous; Leukopenia; Middle Aged; Neoplasm Recurrence, Local; Neutropenia; Oxonic Acid; Stomach Neoplasms; Survival Rate; Taxoids; Tegafur

The purpose of this study was to evaluate the efficacy and safety of a novel oral anticancer fluoropyrimidine derivative, S-1, in patients receiving initial chemotherapy for unresectable, advanced non-small-cell lung cancer (NSCLC). Between June 1996 and July 1998, 62 patients with NSCLC who received no previous chemotherapy for advanced disease were enrolled in this study. Fifty nine patients (22 in stage IIIB and 37 in stage IV) were eligible for the evaluation of efficacy and safety. S-1 was orally administered twice daily after meals. Three doses of S-1 were prescribed according to body surface area (BSA), so that they would be approximately equivalent to 80 mg/m2/day. One cycle of S-1 consisted of consecutive administration for 28 days followed by a 2-week rest, and the cycle was repeated up to 4 times. The partial response (PR) rate of the eligible patients was 22.0% (13/59) (95% confidence interval: 12.3-34.7%). Grade 4 neutropenia was observed in one of the 59 patients (1.7%). There were no irreversible, severe or unexpected toxicities. The median survival time (MST) of all of the patients was 10.2 months (95% confidence interval: 7.7-14.5 months), and the one-year survival rate was 41.1%. S-1 was considered to be an active single agent against NSCLC.

Topics: Administration, Oral; Adult; Aged; Anorexia; Antimetabolites, Antineoplastic; Carcinoma, Non-Small-Cell Lung; Drug Administration Schedule; Drug Combinations; Female; Humans; Lung Neoplasms; Male; Middle Aged; Neutropenia; Oxonic Acid; Quality of Life; Remission Induction; Tegafur

We investigated preoperative chemotherapy with S-1 and low-dose cisplatin for the untreated stage II-IV oral squamous cell carcinoma patients. The chemotherapy consisted of S-1 80 mg/m2/day (day 1-14) and CDDP 5 mg/m2/day (day 1-5 and day 8-12) intravenous drip (less than 1 hour). In the second phase clinical trial of 44 patients, the clinical response rate was 63.7% and the histological response rate by the Oboshi-Shimosato's evaluation was 61.4%. The main adverse events were myelosuppression and gastrointestinal disturbance such as nausea 36.4%, anorexia 27.3%, neutropenia 25% and leukopenia 25%. Grade 3 and 4 adverse events were neutropenia 11.4%, leukopenia 9.1%, thrombocytopenia 4.5% and oligochromemia 4.5%. The two-year overall survival rate was 92.6%. The advantages of this chemotherapy are high response rate, low adverse effects and not to prevent planned therapies such as surgery and radiation. These facts suggest that this chemotherapy is suitable for preoperative chemotherapy.

Topics: Administration, Oral; Adult; Aged; Aged, 80 and over; Anorexia; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Squamous Cell; Cisplatin; Combined Modality Therapy; Drug Administration Schedule; Drug Combinations; Humans; Infusions, Intravenous; Leukopenia; Male; Middle Aged; Mouth Neoplasms; Nausea; Neutropenia; Oxonic Acid; Preoperative Care; Survival Rate; Tegafur

Early and late phase II studies of S-1 were conducted for the treatment of metastatic pancreatic cancer. In both trials, S-1 was administered at a dose of 80 mg/m2/day. One course consisted of consecutive administration of S-1 for 28 days, followed by 14 days of rest. This regimen was repeated every 6 weeks until the occurrence of progressive disease or unacceptable toxicities. The early phase II study demonstrated a response rate of 21.1% with a median survival time of 5.6 months in 19 patients. The major drug-related adverse events were gastrointestinal toxicities like nausea, and anorexia, though most of them were tolerable and reversible. Other treatment-related adverse events, like ileus, colitis, and abdominal distension, were less frequent. The late phase II study confirmed favorable responces with a mild toxicity profile in 40 evaluable patients. S-1 is active and well tolerated in patients with metastatic pancreatic cancer. Randomized trials are warranted to determine the effectiveness of S-1 for the treatment of pancreatic cancer.

Topics: Administration, Oral; Aged; Anorexia; Antimetabolites, Antineoplastic; Drug Administration Schedule; Drug Combinations; Female; Humans; Liver Neoplasms; Lung Neoplasms; Lymph Nodes; Lymphatic Metastasis; Male; Middle Aged; Nausea; Oxonic Acid; Pancreatic Neoplasms; Tegafur

The incidence and mortality of pancreatic cancer has increased very rapidly in Japan. The five-year survival rate is still poor at less than 10%, because it is commonly considered to be linked to a high incidence of distant metastasis even at the initial diagnosis as well as to the tumor's resistance to anticancer agents. Although gemcitabine has been the most widely used chemotherapeutic agent in patients with advanced pancreatic cancer (APC), gemcitabine monotherapy has obvious limitations. Therefore, various combinations with other agents have been investigated to improving the survival of patients with APC. Under these circumstances, we conducted a phase I /II trial of gemcitabine with S-1, an oral fluorouracil derivative, to determine the maximum tolerated dose and to evaluate the activity and toxicity of such a combination in patients with APC. S-1 was administered orally twice daily each day for 14 days and gemcitabine on days 8 and 15 of each cycle, and this cycle was repeated every 21 days. As a result, S-1 30 mg/m2 orally twice daily and gemcitabine 1,000 mg/m2 were selected as the recommended dose. The toxicities observed were mainly hematological ones with mild non-hematological toxicities. An encouragingly high response rate was observed. This result is very promising, but the survival benefit in comparison with gemcitabine monotherapy needs to be confirmed in a future randomized clinical trial.

Topics: Adenocarcinoma; Administration, Oral; Adult; Aged; Anorexia; Antineoplastic Combined Chemotherapy Protocols; Deoxycytidine; Drug Administration Schedule; Drug Combinations; Gemcitabine; Humans; Maximum Tolerated Dose; Middle Aged; Nausea; Oxonic Acid; Pancreatic Neoplasms; Survival Rate; Tegafur; Thrombocytopenia

The therapy 5-FU and CDDP with radiation is thought to be the standard therapy for esophageal cancer patients by now. However, the therapy is associated with a comparatively high incidence of gastrointestinal disorders and requires hospitalization. We have proposed a new regimen of Docetaxel and TS-1 with radiation for maintaining of QOL and improving outcome. Step 1 of the clinical phase I/ II study was conducted for 10 cases from May 2004 to March 2006. Treatment could be accomplished in all cases, and no treatment-related deaths or adverse events of grade 4 were observed in any case. As for hematotoxicity, one case had leucopenia of grade 3 and neutropenia of grade 2. As for non-hematotoxic adverse events, anorexia of grade 3 was recognized in one case of level 3. The response rate evaluated by RECIST was 66% (CR in 2 cases, PR in 4 cases), and the rate based on the Guide Lines for the Clinical and Pathologic Studies on Carcinoma of Esophagus by the Japanese Society for Esophageal Cancer was 70% (CR in 3 cases, PR in 4 cases). We assumed that the recommended dosage of TXT was 30 mg/m(2) and that of TS-1 was 60 mg/m(2) with radiotherapy of 60 Gy. This combination therapy may be recommended because of fewer adverse events and a higher responsive rate than the standard therapies. We intend to continue this study to step 2 and 3, and to reveal the response rate and adverse events for more esophageal cancer patients.

Topics: Aged; Anorexia; Antineoplastic Combined Chemotherapy Protocols; Combined Modality Therapy; Docetaxel; Drug Administration Schedule; Drug Combinations; Esophageal Neoplasms; Humans; Leukopenia; Male; Maximum Tolerated Dose; Middle Aged; Oxonic Acid; Radiotherapy Dosage; Radiotherapy, Adjuvant; Taxoids; Tegafur

The triple combination of 5-fluorouracil (5-FU), vitamin A and radiation (FAR therapy) has been effectively used to treat head and neck cancer. The biological anti-tumor effect of 5-FU depends on the activity of its metabolizing enzyme, dihydropyrimidine dehydrogenase (DPD). TS-1 is a novel oral DPD inhibitory fluoropyrimidine (DIF). To improve the anti-tumor effect of FAR therapy, we have applied TS-1 in place of 5-FU injection in the combination of Vitamin A and radiation (TAR therapy). In this study, we have examined the appropriate duration of TS-1 medication and the clinical efficacy and safety of TAR therapy. TS-1 was administered orally at a dose of 65 mg/m2 twice a day. Vitamin A (Retinol Palmitate: 50,000 U/day) was administered intra-musculary on each day of radiation. Radiation was given (1.5-2 Gy/day: 5 days/week) for 30-40 Gy. The levels were divided according to the length of TS-1 application as follows: level 1, 2 weeks; level 2, 3 weeks; level 4, 4 weeks. Grade 4 toxicity of anorexia was observed in one case of level 3. We decided that level 2 (3 weeks of TS-1 administration) was the appropriate length of TS-1 application. TAR therapy is a useful concurrent chemo-radiotherapy which might improve the response rate and QOL of patients with HNSCC.

Topics: Adult; Aged; Anorexia; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Squamous Cell; Drug Administration Schedule; Drug Combinations; Fluorouracil; Head and Neck Neoplasms; Humans; Maximum Tolerated Dose; Middle Aged; Oxonic Acid; Pyridines; Quality of Life; Radiotherapy Dosage; Tegafur; Vitamin A

A late phase II clinical study of S-1 against advanced or refractory breast cancer was done by 37 institutes in Japan. S-1 was administered twice daily at 80, 100 or 120 mg/body/day consecutively for 28 days followed by 14 days of rest (1 course). Eighty-three patients were enrolled and 81 were eligible for the study. The response ratio was 42.0% with 6 CR and 28 PR and its 95% confidence interval for the response was 31.1 to 53.5%. The median survival period was 910 days (95% confidence interval was 493-1, 083 days). The observed major adverse reactions (> or = grade 2) were as follows: hematological toxicities: leukopenia 21.0% (17/81), neutropenia 28.4% (23/81), erythropenia 4.9% (4/81); gastrointestinal toxicities: anorexia 9.9% (8/81), nausea and vomiting 12.3% (10/81), diarrhea 8.6% (7/81), stomatitis 1.2% (1/81), and fatigue 8.6% (7/81). The severe adverse reactions (> or = grade 3) were as follows; hematological toxicities: neutropenia 8.6% (7/81), anorexia 4.9% (4/81), fatigue 3.7% (3/81), nausea and vomiting 1.2% (1/81), diarrhea 1.2% (1/81), stomatitis 1.2% (1/81). Grade 4 adverse reactions (neutropenia and fatigue) were observed only in 1 patient. The ratio without hospitalization was 87.7%. These results strongly suggest the superior efficacy and safety of S-1 against patients suffering from advanced, refractory breast cancer. Therefore, S-1 may be a new therapeutic agent to prolong the survival period of breast cancer patients due to its high antitumor activity and low toxicity.

Topics: Adult; Aged; Anorexia; Antimetabolites, Antineoplastic; Breast Neoplasms; Diarrhea; Drug Administration Schedule; Drug Combinations; Female; Humans; Leukopenia; Middle Aged; Nausea; Neoplasm Recurrence, Local; Neutropenia; Oxonic Acid; Pyridines; Tegafur; Vomiting, Anticipatory

The efficacy and safety of the oral fluoropyrimidine TS-1, which contains a dihydropyrimidine dehydrogenase (DPD) inhibitor, were examined in fifty-five patients with gastric cancer. The patients were divided into 28 with measurable cancer lesions (TUM group) and 27 without them (ADJ group). The total number of courses was 164 (mean: 5.9 courses) in the TUM group and 146 (mean; 5.4 courses) in the ADJ group. The response rate in the TUM group, excluding three patients who could not be evaluated because of incomplete administration, was 40% (CR: 4, PR: 6, NC: 6, PD: 9). Among responders, the mean number of courses to response was 2.2 and the median survival time (MST) was 21.7 months. In terms of safety, adverse reactions appeared in forty-five patients (82%) and the incidence was higher in the ADJ group. Major toxicities were leukopenia (38%), anorexia (27%), increased total bilirubin concentration (25%) and diarrhea (24%). Adverse reaction of grade 3 was found in only three patients (5.5%) and there were no drug-related deaths. In conclusion, TS-1 is safe and effective if attention is given to biweekly examinations for the development of adverse reactions.

Topics: Administration, Oral; Adult; Aged; Anorexia; Antimetabolites, Antineoplastic; Bilirubin; Drug Administration Schedule; Drug Combinations; Female; Humans; Leukopenia; Male; Middle Aged; Neoplasm Recurrence, Local; Oxonic Acid; Postoperative Period; Pyridines; Stomach Neoplasms; Tegafur

In developing new anticancer agents, the most important thing is the balancing of antitumor activity and toxicity. To achieve high activity and low toxicity, S-1 was designed, in which tegafur, prodrug of 5-FU, was combined with two classes of modulators. CDHP, inhibitor of 5-FU degradation in liver and Oxo, inhibitor of 5-FU phosphoribosylation in digestive tract, respectively. This cooperative study with 15 nation-wide institutes was conducted to evaluate the antitumor activity and toxicity of S-1 in patients with advanced head and neck cancer from Jan. 1994 to March 1996 in Japan. Out of 26 patients, CR was achieved in 1 and PR in 11 with a response rate of 46.2%, while adverse events of grade 3 were as follows: hemoglobinemia (7.7%), leukocytopenia, neutropenia, stomatitis and anorexia (3.8%), each. Neither grade 4 adverse event nor treatment-related deaths were observed. Based on these findings, it was concluded that S-1 is a useful anticancer agent with the low grade toxicities for treatment of the patients with advanced head and neck cancer, and the effects of CDHP and Oxo found in preclinical studies might be also reflected in these results.

Topics: Administration, Oral; Adult; Aged; Anorexia; Antimetabolites, Antineoplastic; Carcinoma, Squamous Cell; Drug Administration Schedule; Drug Combinations; Female; Head and Neck Neoplasms; Humans; Leukopenia; Lymphatic Metastasis; Male; Middle Aged; Neutropenia; Oxonic Acid; Pyridines; Stomatitis; Tegafur

S-1 monotherapy with concurrent radiotherapy (RT) is a standard of care for patients with locally advanced pancreatic cancer (LAPC). Although renal dysfunction increases S-1 monotherapy toxicity, its effect in S-1 with concurrent RT remains unknown. We evaluated the effect of renal function on the safety of S-1 with RT for LAPC.. We performed an integrated exploratory post hoc analysis of data from 2 prospective studies (JCOG1106 and LAPC-S1RT), where patients with LAPC received RT (50.4 Gy/28 fraction for 5.5 weeks) and concurrent S-1 (40 mg/m2 per dose, twice daily on the day of irradiation). We split the patients into high creatinine clearance (CCr; ≥80 mL/min) and low CCr (<80 mL/min) groups and compared the findings to determine treatment safety.. The high and low CCr groups showed a median of 97.5 (range, 80.0-194.6) and 64.4 (range, 50.0-78.3) mL/min, respectively. The low CCr group presented more adverse reactions (ARs) of grade 3 or higher and gastrointestinal ARs of grade 2 or higher than the high CCr group (30.8% vs 15.8% and 51.9% vs 36.8%).. The incidence of ARs associated with concurrent S-1 and RT increases in patients with low CCr; therefore, ARs should be duly considered in such patients.

Topics: Aged; Anorexia; Antimetabolites, Antineoplastic; Chemoradiotherapy; Clinical Trials as Topic; Drug Combinations; Female; Humans; Kaplan-Meier Estimate; Kidney; Kidney Function Tests; Male; Middle Aged; Nausea; Outcome Assessment, Health Care; Oxonic Acid; Pancreatic Neoplasms; Radiotherapy; Tegafur; Vomiting

The prognosis for locally advanced gastric cancer (AGC) remains unsatisfactory, even with S-1 adjuvant chemotherapy. We investigated the efficacy of neoadjuvant chemotherapy consisting of docetaxel, cisplatin and S-1 (DCS).. We retrospectively reviewed 59 patients who underwent neoadjuvant DCS therapy for clinical stage III tumors or serosa-positive tumors between January 2009 and December 2013 at Niigata Cancer Center Hospital. The patients received S-1 (40 mg/m(2) bid) on days 1-14, and docetaxel (35 mg/m(2)) and cisplatin (35 mg/m(2)) on days 1 and 15 every 4 weeks.. Forty-three patients (72.9 %) received two courses of DCS therapy, while 16 patients (27.1 %) received one course of treatment. The clinical response rate of the primary tumor was 74.6 %, and the disease control rate was 100 %. A pathological response, defined as one-third or more of the affected tumor, was observed in 71.2 % of patients. The common grade 3/4 adverse events from chemotherapy were leucopenia (16.9 %), neutropenia (44.1 %), febrile neutropenia (8.5 %), anemia (10.2 %), anorexia (8.5 %) and nausea (6.8 %). Postoperative complications occurred in 11 patients (18.6 %). There was no treatment-related mortality or reoperation. The 3- and 5-year overall survival rates were 88 and 68.6 %, respectively. Clinical responders had a significantly higher survival rate than non-responders. Multivariate analysis identified clinical response as the only independent prognostic factor.. Neoadjuvant DCS therapy demonstrated a very high clinical and pathological response rate with acceptable toxicities. Therefore, this therapy may improve the prognosis of locally AGC.

Topics: Adult; Aged; Aged, 80 and over; Anemia; Anorexia; Antineoplastic Combined Chemotherapy Protocols; Chemotherapy, Adjuvant; Cisplatin; Docetaxel; Drug Combinations; Febrile Neutropenia; Female; Gastrectomy; Humans; Male; Middle Aged; Nausea; Neoadjuvant Therapy; Neoplasm Staging; Oxonic Acid; Prognosis; Retrospective Studies; Stomach Neoplasms; Survival Rate; Taxoids; Tegafur

A 78-year-old woman was admitted to our hospital complaining of anorexia and purpura of the extremities. She presented with prominent peripheral eosinophilia and disseminated intravascular coagulation (DIC). Despite receiving intensive therapy for DIC, her illness worsened. Esophagogastroduodenoscopy revealed advanced gastric cancer (AGC), and a bone marrow biopsy led to a diagnosis of disseminated carcinomatosis of the bone marrow caused by AGC. We initiated combination chemotherapy with S-1 and cisplatin, which lead to a significant improvement of the DIC and eosinophilia, and the patient was finally discharged. The primary symptoms of DIC and eosinophilia were both considered to be caused by AGC, and we successfully treated the patient's critical condition.

Topics: Aged; Anorexia; Antineoplastic Combined Chemotherapy Protocols; Biopsy; Bone Marrow; Bone Marrow Neoplasms; Cisplatin; Disseminated Intravascular Coagulation; Drug Combinations; Eosinophilia; Female; Humans; Oxonic Acid; Purpura; Stomach Neoplasms; Tegafur; Treatment Outcome

This paper presents a man in his 80's with pancreatic cancer(cStage IV). He suffered from nausea duringS -1 therapy, and therefore, prochlorperazine maleate at a daily dose of 15 mgwas administered. However, refractory nausea was diagnosed because it did not improve, and mirtazapine at a daily dose of 7. 5 mgbefore bedtime was started. Nausea was improved in the next morning, and the patient ate almost all of his breakfast. After that, no nausea appeared, and his food intake was robust. Mirtazapine is a new antidepressant called noradrenergic and specific serotonergic antidepressant(NaSSA)and blocks 5-HT3 receptors to improve nausea. Mirtazapine is usually started at a daily dose of 15 mg, but this dose induces somnolence. Therefore, mirtazapine was administered at a low daily dose of 7. 5 mgin the present case. No somnolence or disturbance of daily life was seen, and administration was safely continued. We conclude that low-dose mirtazapine is one effective option for refractory nausea duringS -1 therapy.

Topics: Aged, 80 and over; Anorexia; Antimetabolites, Antineoplastic; Drug Combinations; Histamine H1 Antagonists; Humans; Male; Mianserin; Mirtazapine; Nausea; Neoplasm Staging; Oxonic Acid; Pancreatic Neoplasms; Tegafur

To improve the prognosis of locally advanced gastric cancer, clinical trials of neoadjuvant chemotherapy (NAC) are being performed. Although neoadjuvant chemoradiotherapy (NACRT) generally achieves superior local tumor control to NAC, its efficacy for locally advanced gastric cancers remains unclear. Therefore, a prospective trial was conducted to explore the feasibility and safety of NACRT with oral S-1 in a series of cases.. Patients who had Japanese Gastric Cancer Association (JGCA) cStage IIIB gastric cancer were enrolled onto this study and received oral S-1 (65 mg/m(2)/day) administration and 50-Gy radiotherapy followed by radical surgery. The primary end points were completion of therapy and safety.. Between October 2005 and September 2008, 12 eligible patients were enrolled. Two could not complete the chemotherapy because of grade 3 toxicity. R0 resections were performed in 11 patients (91.7 %) (95 % confidence interval 61.5-99.8). Although operative morbidity was observed in two cases, there were no postoperative deaths. A pathologic response was observed in 10 patients (83.3 %). In five (62.5 %) of eight gastric cancers with invasion to adjacent structures, microscopic tumor deposits were not found in the affected organs. The 3-year survival rate was 58.3 % during a median follow-up period of 36 months.. Although this study is preliminary, the present regimen seems to be feasible and safe as a treatment for locally advanced gastric cancers featuring adjacent tissue invasion or JGCA bulky N2 disease. This treatment approach should now be tested using the new tumor, node, metastasis staging system in a large clinical trial.

Topics: Adenocarcinoma; Aged; Aged, 80 and over; Anorexia; Antimetabolites, Antineoplastic; Chemoradiotherapy, Adjuvant; Dose Fractionation, Radiation; Drug Combinations; Female; Gastrectomy; Humans; Kaplan-Meier Estimate; Lymph Node Excision; Lymphatic Metastasis; Male; Middle Aged; Nausea; Neoadjuvant Therapy; Neoplasm Grading; Neoplasm Staging; Oxonic Acid; Pilot Projects; Stomach Neoplasms; Tegafur

The combination of oxaliplatin and S-1 is effective in patients with advanced gastric cancer. The purpose of this study was to analyze the safety and compliance of this combination regimen as adjuvant chemotherapy in patients with gastric cancer.. Clinical data of 71 patients with gastric cancer treated with oxaliplatin plus S-1 as adjuvant chemotherapy in the Cancer Hospital, Chinese Academy of Medical Sciences (CAMS) from Jan 1(st), 2010 to Jan 1(st), 2012 were retrospectively reviewed. The types and incidence rate of adverse events related to chemotherapy and the results of follow up of the patients were analyzed.. Among the 71 cases, 17 were treated with oxaliplatin biweekly, while 54 with oxaliplatin triweekly. The most common adverse events were neutropenia (n = 49, 69.0%), nausea/vomiting (n = 51, 71.8%), and anorexia (n = 49, 69.0%). The most frequent grade 3-4 toxicities were neutropenia (n = 13, 18.3%), thrombocytopenia (n = 10, 14.1%), anorexia (n = 5, 7.0%) and nausea/vomiting (n = 4, 5.6%). Seven (87.5%) of the 8 patients previously treated with neoadjuvant chemotherapy experienced thrombocytopenia in the postoperative adjuvant chemotherapy, and four (50%) of the 8 patients experienced grade 3-4 thrombocytopenia. The rates of grade 3-4 adverse events in patients aged 65-years or older were similar to that in younger patients.. The combination of oxaliplatin and S-1 used as adjuvant chemotherapy is well tolerated by patients with gastric cancer. Neutropenia, thrombocytopenia, nausea/vomiting and anorexia are the major treatment-related adverse events. Patients who received neoadjuvant chemotherapy do not well tolerate this regimen as postoperative adjuvant chemotherapy. This combination regimen has a manageable tolerability profile in adjuvant setting in patients ≥ 65 years old.

Topics: Adenocarcinoma; Adult; Aged; Anorexia; Antineoplastic Combined Chemotherapy Protocols; Chemotherapy, Adjuvant; Drug Combinations; Female; Follow-Up Studies; Humans; Male; Middle Aged; Nausea; Neoadjuvant Therapy; Neoplasm Staging; Neutropenia; Organoplatinum Compounds; Oxaliplatin; Oxonic Acid; Retrospective Studies; Stomach Neoplasms; Survival Rate; Tegafur; Thrombocytopenia

Dihydropyrimidine dehydrogenase (DPD) is a reducing enzyme for fluoropyrimidine which is a widely-used anti-cancer agent, and its deficiency leads to serious toxicities. We report a rare patient with a DPD deficiency. A 39-year-old man was suspected to have a gastric cancer recurrence from the elevation of CEA. Although TS-1 was administered for five days, it was stopped due to the development of grade 2 anorexia and nausea. Although we administered UFT at his request after a one-month drug rest, grade 1 stomatorrhagia besides the former adverse events developed after five days. Therefore he discontinued it and was admitted to our hospital. After 19 days, he died from multiple brain hemorrhage despite the intensive therapies. We considered that the congenital DPD deficiency caused the development of these adverse events because the DPD value was less than 5 pmol/mg/min in mononuclear cells of peripheral blood.

Topics: Adult; Anorexia; Antimetabolites, Antineoplastic; Bone Neoplasms; Cerebral Hemorrhage; Dihydropyrimidine Dehydrogenase Deficiency; Drug Combinations; Fatal Outcome; Humans; Liver Neoplasms; Male; Nausea; Oxonic Acid; Stomach Neoplasms; Tegafur; Uracil

The aim of this survey was to confirm the safety and efficacy of S-1 for advanced gastric cancer after market release.. All patients had to be registered with the manufacturer for a post-marketing survey, according to the government recommendation. All patients were monitored for safety and survival.. During this survey, a total of 4,177 patients with advanced gastric cancer were registered. The incidences of all adverse events and of grade 3 or worse events in the 3,808 patients evaluable for safety were 74% and 25%, respectively. In patients with lower creatinine clearance at baseline, the incidences of adverse reactions were higher for all grades combined, as well as for grade 3 or worse. There were 90 (2.4%) early deaths (within 30 days of the initiation of the treatment) and 5 (0.1%) deaths possibly related to the treatment. The median survival time and the 1-year survival rate for all patients evaluable for efficacy (n=3,801) were 8.3 months (95% CI: 8.0-8.6 months) and 33.3% (95% CI: 31.8-34.9%), respectively.. This nationwide survey confirmed that the safety and efficacy profiles of S-1 were similar to those seen in the registration study.

Topics: Aged; Anorexia; Antimetabolites, Antineoplastic; Drug Administration Schedule; Drug Combinations; Drug Monitoring; Female; Humans; Japan; Leukopenia; Male; Middle Aged; Neutropenia; Oxonic Acid; Product Surveillance, Postmarketing; Registries; Stomach Neoplasms; Survival Rate; Tegafur

We report a case of non-curatively resected gastric cancer successfully treated with TS-1 and irinotecan (CPT-11) combination therapy, resulting in long-term survival of 17 months. A 56-year-old woman underwent noncurative resection with total gastrectomy for advanced gastric cancer with severe lymph node metastasis on June 3, 2004. Postoperatively, She received TS-1 and CPT-11 combination therapy (TS-1 80 mg/m(2) day 1-21, CPT-11 80 mg/m(2) day 1, 15, every 5 weeks). However, due to grade 4 neutropenia, and grade 3 nausea and anorexia in the first course, both doses were reduced. Since then, no grade 3 or severer adverse reactions have been observed. After 5 courses, partial response to lymph node metastasis was obtained, and her quality of life was improved. Thus, TS-1 and CPT-11 combination therapy has been effective for 17 months, suggesting that it is promising for long-term administration and survival to continue it perseveringly.

Topics: Anorexia; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Combined Modality Therapy; Drug Administration Schedule; Drug Combinations; Female; Gastrectomy; Humans; Irinotecan; Lymph Nodes; Lymphatic Metastasis; Middle Aged; Nausea; Neutropenia; Oxonic Acid; Quality of Life; Stomach Neoplasms; Survivors; Tegafur

We report two metastatic pancreatic cancer patients who showed marked tumor shrinkage following administration of the oral fluorinated pyrimidine anticancer drug, S-1. In the early phase II trial of S-1 for metastatic pancreatic cancer, both patients showed a partial response (Japan Society for Cancer Therapy Criteria): the reduction ratio of the tumor volume was 81.4% in the patient with liver metastasis (Case 1) and 86.9% in the patient with lung metastasis (Case 2). Case 1 showed grade 3 anorexia and decrease of the serum hemoglobin as severe adverse effects, but the other adverse reactions were mild. Both patients could be treated as outpatients. S-1 showed a promising antitumor effect and tolerability in patients with metastatic pancreatic cancer, and it was also considered to be beneficial for patients in terms of convenience of administration, that is, by the oral route.

Topics: Adenocarcinoma; Aged; Anorexia; Antimetabolites, Antineoplastic; Clinical Trials, Phase II as Topic; Drug Administration Schedule; Drug Combinations; Female; Hemoglobins; Humans; Liver Neoplasms; Lung Neoplasms; Middle Aged; Oxonic Acid; Pancreatic Neoplasms; Tegafur

We used TS-1 as first-line therapy to treat 44 patients with far advanced or recurrent gastric cancer, and assessed the results and safety. One treatment cycle consisted of TS-1, 80 mg/m2/day, for 28 days followed by a 14-day rest period. The efficacy rate in the cases capable of being evaluated was 30.1% (11/36), and 25.0%, (7/28) when TS-1 was used as monotherapy. The efficacy rate was lower than in a phase II study, however, the median survival time (MST) of 10.7 months for the patients as a whole, the 1-year survival rate of 43.2%, and the 2-year survival rate of 20.5% were favorable. There were many NC cases in which long-term therapy was possible, and they contributed to the long-term survival. The incidence of adverse events was 84.1%, but the incidence of grade 3 or more events was low at 13.6%. Since TS-1 is highly efficacious and safe, as well as convenient because of being an oral preparation, it appears that it can be ranked as the drug of first choice for chemotherapy of far advanced or recurrent gastric cancer.

Topics: Adult; Aged; Aged, 80 and over; Anorexia; Antimetabolites, Antineoplastic; Drug Administration Schedule; Drug Combinations; Female; Humans; Male; Middle Aged; Neoplasm Recurrence, Local; Oxonic Acid; Pyridines; Stomach Neoplasms; Survival Rate; Tegafur; Treatment Outcome

We report two resected cases of advanced gastric cancer with peritoneal dissemination after successful treatment with TS-1 plus low-dose CDDP. Patient 1 presented with right hypochondralgia and underwent laparotomy with diagnosis of type 4 gastric cancer by gastrointestinal fiberscopy. However, the tumor was judged to be unresectable due to peritoneal dissemination, and chemotherapy was performed. At the completion of course 1, he underwent laparotomy again. Although the tumor involved the body of the pancreas and transverse colon, there was no peritoneal dissemination. Therefore, a total gastrectomy was performed with distal pancreatectomy, partial colectomy, cholecystectomy, and D2 lymph node dissection. Patient 2 presented with anorexia and was diagnosed with type 3 gastric cancer by gastrointestinal fiberscopy. CT revealed the tumor was unresectable due to peritoneal dissemination, and so chemotherapy was performed. He underwent laparotomy at the completion of course 3. There was no peritoneal dissemination, so a total gastrectomy was performed with cholecystectomy and D2 lymph node dissection. Both patients remain alive and in good condition without any signs of recurrence after surgery.

Topics: Aged; Anorexia; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Combinations; Gastrectomy; Humans; Male; Middle Aged; Oxonic Acid; Peritoneal Neoplasms; Pyridines; Stomach Neoplasms; Tegafur