Phase I/II study of combination chemotherapy with gemcitabine and UFT for advanced pancreatic cancer in a multi-center trial

The aim of this phase I/II study was to evaluate the tolerability and efficacy of combination chemotherapy with gemcitabine (GEM) and UFT for advanced pancreatic cancer. In phase I study UFT was given orally every day for 14 days and GEM was infused on day 1 and 8 at three dose levels (800, 900, 1,000 mg/m(2)/week) every 21 days. GEM 1,000 mg/m(2) and UFT 400 mg/m(2) did not reach the maximum tolerated dose. We decided that the recommended dose (RD) was GEM 1,000 mg/m(2)and UFT 400 mg/m(2). In phase II study 27 patients were enrolled and received GEM and UFT at RD. The tumor response rate was 17.6%, and the median survival was 221 days, which was very similar to that of GEM monotherapy. Due to adverse events, especially liver dysfunction, protocol therapy was discontinued in 12 patients. This study could not revealed the superiority of the GEM monotherapy.     

A phase II study of epirubicin, cisplatin and uracil-tegafur for advanced gastric carcinoma

BACKGROUND: Due to its greater convenience, a combination of uracil and tegafur (referred to as UFT) taken orally is an attractive alternative to continuous intravenous (i.v.) 5-fluorouracil (5-FU) infusion. This phase II study assessed the response rate and toxicity profile of the combination of epirubicin, cisplatin and UFT in patients with metastatic adenocarcinoma of the stomach. METHODS: Epirubicin (50 mg/m(2)) and cisplatin (60 mg/m(2)) were administered i.v. to 35 patients with metastatic gastric carcinoma on day 1, and subsequently UFT (300 mg/m(2)/day) was administered orally in divided doses for 21 days. The treatment was repeated every 3 weeks. The response rate, time to disease progression, survival and toxic effects were analyzed. RESULTS: Thirty-two of the 35 enrolled patients were assessed subsequently for response. The median number of cycles was four. Thirteen patients (40.6%) showed partial responses, while none showed a complete response. The median time to progression of carcinoma was 20.4 weeks, and the median survival was 37 weeks. Grade 3 and 4 neutropenia was observed in 25% of patients. Grade 3 nausea and vomiting was observed in 28% of patients. No treatment-related death was observed. All patients received doses as planned, except for one who required a 75% dose reduction due to nephrotoxicity. Six of 132 cycles were delayed >7 days after four cycles. CONCLUSIONS: The combination of epirubicin, cisplatin and UFT showed anticancer activity against metastatic gastric adenocarcinoma, had a tolerable toxicity profile and showed excellent patient compliance.     

A phase I/II study of high-dose cyclophosphamide,cisplatin, and thioTEPA followed by autologous bone marrow and granulocyte colony-stimulating factor-primed peripheral-blood progenitor cells in patients with advanced malignancies

 The purpose of the present study was to determine the maximally tolerated dose of thioTEPA given with fixed high-dose cyclophosphamide (CPA) and cisplatin (cDDP) followed by autologous bone marrow (ABM) with or without granulocyte colonystimulating factor (G-CSF)-primed peripheral-blood progenitor cells (PBPCs) in patients with advanced malignancies. Patients were required to have histologically documented malignancies and adequate renal, hepatic, pulmonary, and cardiac function. CPA was given at 1,875 mg/m² per day as a 1-h i.v. infusion for 3 consecutive days, and cDDP was given at 55 mg/m² per day as a 24-h continuous i.v. infusion over 3 days concurrently with CPA. ThioTEPA was given once as a 1-h i.v. infusion (300–900 mg/m²) either following (the first 13 patients) or prior to CPA and cDDP. In all, 31 patients received PBPCs. A total of 46 patients were treated. There were 6 deaths among the 15 patients who did not receive PBPCs (13 received thioTEPA following CPA and cDDP). Among the other 31 patients who received PBPCs (all of whom also received thioTEPA prior to CPA and cDDP), there were 4 deaths, all involving patients with refractory ovarian carcinoma. The main toxicities were mucositis, esophagitis, hepatotoxicity, and nephrotoxicity. The median time required to achieve an absolute neutrophil count of 500 μl was 10 days (range, 9–12 days) for those who received PBPCs and 15 days (range, 15–34 days) for those who did not receive PBPCs. Altogether, 47% of the major organ toxicities (grades 3 and 4 renal, hepatic, and cardiac toxicities) occurred among the 15 patients who did not receive PBPCs, although these patients received thioTEPA at the lowest 2 dose levels. There were 3 complete responses and 22 partial responses among 35 evaluable patients (overall response rate, 71%), with the median duration of response being 3.5 months (range, 2–17 months). The maximally tolerated dose of thioTEPA was 600 mg/m² given as a 1-h i.v. infusion on the day prior to CPA and cDDP administration. The combination of high-dose CPA, cDDP, and thioTEPA is a well-tolerated regimen when thioTEPA is given prior to CPA and cDDP and when the combination also includes PBPCs in addition to ABM. This regimen is active in a variety of malignancies. Received: 15 February 1995/Accepted: 22 May 1995     

Phase I study of gemcitabine (GEM) and UFT combination chemotherapy for unresectable/recurrent pancreatic cancer

A phase I study of gemcitabine (GEM) and UFT combination chemotherapy was performed for unresectable pancreatic cancer. The regimen included UFT orally from day 1 through day 6 and from day 8 through 13, GEM intravenously on day 7 and 14, and 1 week rest as 1 course. Administration of more than 2 courses was attempted for each patient, with the same dosage levels at all 3 scheduled steps. Nine patients were enrolled in the study. Leukopenia and neutropenia of grade 3 occurred in 2 of 6 patients at level 2, and maximum tolerated dose (MTD) was considered to be 800 mg/m2 for GEM and 250 mg/m2 for UFT. Clinical effects of the patients included: 2 PR, 4 NC, and 3 PD, for a response rate of 22% (2/9 patients). Reduced CA19-9 level of less than half of that at starting time was observed in 4 of 9 (44%) patients. The recommended dose for the phase II study is GEM 800 mg/m2 and UFT 250 mg/m2 with consideration of application to outpatients and continuing courses.     

Epirubicin, cisplatin and oral UFT with leucovorin (''ECU''): a phase I-II study in patients with advanced upper gastrointestinal tract cancer.

Background: ECF (epirubicin, cisplatin, protracted venous fluorouracil) is superior to FAMTX in gastroesophageal cancer, but protracted fluorouracil adds to its morbidity and cost. In this dose-escalation pilot study, fluorouracil was replaced by oral UFT and leucovorin.Patients and methods: Thirty unpretreated patients with advanced upper gastrointestinal cancers received epirubicin 50 mg/m² and cisplatin 60 mg/m² i.v. on day 1, and leucovorin 45 mg p.o. on days 1, 8 and 15, of a 21-day cycle for up to 8 cycles. UFT was taken 12-hourly throughout, at escalating doses in four cohorts ranging from 150–325 mg/m² per day.Results: The maximum tolerable dose of UFT, recommended for further study, was 200 mg/m² per day. At higher doses, more than two-thirds patients required dose reductions, although mostly for persistent mild (CTC grade 2) nausea, diarrhoea or fatigue, rather than for severe acute toxicity. Myelotoxicity was mild. Twenty patients, including 15 with gastroesophageal cancer, had assessable disease. Among these there were nine WHO objective responses, all in gastroesophageal patients, including two radiological complete responses.Conclusions: ECU is well tolerated at the defined dose, with activity comparable to ECF in gastroesophageal cancer. UFT and other oral 5FU dosing strategies make promising components of combination chemotherapy, deserving further, randomised evaluation.     

Phase I trial of weekly irinotecan combined with UFT as second-line treatment for advanced colorectal cancer

The aim of this study was to determine the maximum-tolerated dose (MTD) and dose-limiting toxicity (DLT) of weekly Irinotecan (CPT-11) plus UFT, and to assess the antitumour activity of this combination as second-line chemotherapy in patients with advanced colorectal carcinoma, 31 patients with measurable advanced colorectal carcinoma were treated. Cohorts of 3 patients received increasing dose levels of the combination. Levels 1 to 4 included a fixed dose of oral (p.o.) UFT (250 mg/m²/day) for 21 days of a 28-day cycle combined with increasing intravenous (i.v.) doses of CPT-11 (80, 100, 110 and 120 mg/m²) on days 1, 8 and 15. Levels 5 and 6 included a higher fixed dose of oral UFT (300 mg/m²) combined with increasing i.v. doses of CPT-11 (100 and 110 mg/m²) on days 1, 8 and 15. 147 courses were administered. MTD were reached at level 4 (2 cases of grade 4 diarrhoea and 1 grade 3 asthenia), and level 6 (1 grade 4 diarrhoea, 1 grade 3 diarrhoea and 1 grade 3 febrile neutropenia). Responses in 30 evaluable patients were: 3 partial responses (10%), 15 stable disease (50%) and progressive disease in 12 patients (40%). Median time to progression was 4.5 months (95% Confidence Interval (CI): 3.4–6.6 months) and median survival was 11 months (95% CI: 7.9–14.1 months). The recommended doses for phase II trials are: (a) CPT-11 110 mg/m² i.v. on days 1, 8 and 15 every 28 days plus UFT 250 mg/m² p.o. on days 1 through to 21 or (b) CPT-11 100 mg/m² and UFT 300 mg/m².     

Phase II study of gemcitabine, UFT and leucovorin in patients with advanced pancreatic cancer

The combination of gemcitabine with protracted 5-fluorouracil (5-FU) in the treatment of metastatic pancreatic cancer has shown activity with tolerable toxicity. The administration of UFT may simulate the effects of a protracted infusion of 5-FU. Patients with previously untreated metastatic or unresectable measurable pancreatic adenocarcinoma received gemcitabine (800 mg/m2 i.v., administered as an 80-min infusion on days 1, 8 and 15), UFT (200 mg/m2/day, on days 1 to 21), and oral leucovorin (90 mg/day, on days 1 to 21). Thirty patients were enrolled in this study. Five patients had partial responses, with an overall response rate of 17% (5/30), using the intent-to-treat principle (95% confidence interval (CI), 3-30%). Nine out of 25 (36%) patients experienced clinical benefit responses (95% CI; 17-55%). The median time to progression was 3.0 months, and the median overall survival was 7.2 months. The principal adverse event was neutropenia. The combination of gemcitabine, UFT, plus oral leucovorin shows significant antitumor activity and a beneficial clinical effect with an acceptable level of toxicity.     

Phase II Study of Gemcitabine, UFT and Leucovorin in Patients with Advanced Pancreatic Cancer

The combination of gemcitabine with protracted 5-fluorouracil(5-FU) in the treatment of metastatic pancreatic cancer has shown activity with tolerable toxicity. The administration of UFT may simulate the effects of a protracted infusion of 5-FU. Patients with previously untreated metastatic or unresectable measurable pancreatic adenocarcinoma received gemcitabine (800 mg/m2 i.v., administered as an 80-min infusion on days 1, 8 and 15), UFT (200 mg/m2/day, on days 1 to 21), and oral leucovorin (90 mg/day, on days 1 to 21). Thirty patients were enrolled in this study. Five patients had partial responses, with an overall response rate of 17% (5/30), using the intent-to-treat principle (95% confidence interval (CI), 3-30%). Nine out of 25 (36%) patients experienced clinical benefit responses (95% CI; 17-55%). The median time to progression was 3.0 months, and the median overall survival was 7.2 months. The principal adverse event was neutropenia. The combination of gemcitabine, UFT, plus oral leucovorin shows significant antitumor activity and a beneficial clinical effect with an acceptable level of toxicity.     

High-dose oral tegafur-uracil maintenance therapy in patients with uterine cervical cancer

ObjectiveThe aim of this study was to determine the efficacy and toxicity of oral administration of tegafur-uracil (UFT) at a high dose, 600 mg/day, based on the tegafur dose, against uterine cervical cancer.MethodsThis study consisted of a retrospective analysis. From April 1986 to March 1997, 309 patients with uterine cervical cancer were registered. Oral UFT was administered to 162 patients for maintenance therapy after an initial treatment (the UFT group). The other 147 patients were not treated with UFT (the control group). The survival rate was calculated for both groups and statistically analyzed using the log-rank test. Adverse events were compared between the UFT and control groups.ResultsIn the UFT group, 103 patients (63.6%) received UFT for ≥90 days. The drug dose was 600 mg/day for 137 patients (84.6%) and 300 to 400 mg/day for the remainder. The overall survival rate was significantly higher in the UFT group than in the control group (p<0.05). The prognosis was particularly favorable in stage III cases, in cases of squamous cell carcinoma, and in cases that were treated by radiotherapy. The most frequent side effects were nausea/vomiting (12.2%), appetite loss (10.1%), and leukopenia/neutropenia (5.8%).ConclusionHigh-dose oral UFT maintenance treatment prolonged the disease-free survival and overall survival of patients with uterine cervical cancer, particularly of those with advanced disease.     

Efficacy and Safety of Raltitrexed Combinations with Uracil-Tegafur or Mitomycin C as Salvage Treatment in Advanced Colorectal Cancer Patients: A Multicenter Study of Anatolian Society of Medical Oncology (ASMO)

Background: There is no standard treatment for patients with colorectal cancer (CRC) progressing afteririnotecan and oxaliplatin treatment. Here we aimed to retrospectively evaluate the efficacy and tolerability ofraltitrexed in combination with oral 5-fluoropyrimidine (uracil tegafur-UFT) or mitomycin C as salvage therapyin mCRC patients. Materials and Methods: A total of 62 patients who had received raltitrexed combined withUFT or mitomycin C were identified between December 2008 and June 2013. They were given raltitrexed 2.6mg/m2 (max 5 mg) i.v. on day 1 in combination with either oral UFT 500 mg/day on days 1-14 every 3 weeks(group A) or mitomycin C 6 mg/m2 i.v. on day every 3 weeks (group B). Results: Forty-two patients (67.7%)were in group A and 20 (32.2%) in group B. In 15 patients (24%) grade 3/4 toxicity was observed, resultingin dose reduction, and in 13 patients (20.9%) dose delay was necessary. The median progression free survival(PFS) was 3 months (95%CI 2.65-3.34) and median overall survival (OS) was 6 months (95%CI 2.09-9.90) inthe whole group. Median PFS was 3 months (95%CI 2.60-3.39) in group A vs 3 months (95%CI 1.64-4.35) ingroup B (p=0.90). Median OS was 6 months (95%CI 2.47-9.53) in group A vs 12 months (95%CI 2.83-21.1) ingroup B (p=0.46). Conclusions: The combination of raltitrexed with UFT or mitomycin C seem to be a salvagetherapy option due to safety profile and moderate clinical activity in heavily-pretreated mCRC patients.     

UFTM联合治疗晚期胃癌140例分析

140 patients with advanced gastric cancer confirmed by pathology were treated by UFT (Uracil, FT-207) and mitomycin C (MMC) from Sept. 1985 to June 1987. All the patients received UFT #3 T. i. d. to a total dose of 30 g. Mitomycin C, 8-20 mg i. v. Q. wk was given to a total dose of 48-60 mg. Of the 140 patients, 65 had cancer of cardia, 36 cancer of gastric body, and 39 cancer of gastric antrum. There were 125 males and 15 females. The ages ranged from 30 to 80 years. In this series, CR was 10.0% and PR 44.3% with total remission rate of 54.3% (76/140). Thirty-four patients receiving UFT alone as control had a response rate of 26.5%. The response rate was higher in patients treated with UFTM than those with UFT alone. The median remission was 4 months. That main side effects were leukopenia and thrombocytopenia. The results showed that combination chemotherapy (UFTM) was valid in treating advanced gastric cancer.     

Expression of orotate phosphoribosyl transferase in human pancreatic cancer: implication for the efficacy of uracil and tegafur-based adjuvant chemotherapy

The enzyme orotate phosphoribosyl transferase (OPRT) is involved in the metabolism of the anticancer drug 5-fluorouracil (5-FU), and is a key enzyme for conversion of 5-FU to its active form in tumor tissue. Little is known regarding the significance of OPRT in human pancreatic cancer. The present study was designed to assess the association between the activity of OPRT in the tumor, and the clinicopathological status and prognosis of human resectable pancreatic cancer, especially regarding its relevance to the efficacy of adjuvant chemotherapy with uracil and tegafur (UFT), cyclophosphamide (CPA) and/or gemcitabine (GEM). The present study included 99 resectable pancreatic cancers, which were all invasive ductal tubular carcinomas. OPRT was immunostained with a rabbit anti-human OPRT polyclonal antibody. OPRT was positively stained in 54 (54.5%) of 99 pancreatic cancers. The post-surgical survival rate of the OPRT (+) pancreatic cancers was significantly higher than that of the OPRT (-) ones. In the OPRT (+) group, the survival rate of the patients, who received adjuvant chemotherapy (ACT) with UFT, CPA or GEM, was significantly higher than that of the patients without ACT; however, in the OPRT (-) group, there was no difference in the survival between the ACT (+) and (-) groups. Multivariate analyses demonstrated that for all patients, primary tumor, status of nodal involvement (pN), residual tumor, level of dissection and CPA were significant variables for the prognosis: in OPRT (+) groups, primary tumor, nodal involvement, GEM and CPA were significant variables. In contrast, in the OPRT (-) group, pN was the only significant variable. The present study is the first report on the significance of OPRT in human pancreatic cancer, and the results indicate that the expression of OPRT may be useful to predict the response to adjuvant chemotherapy in human pancreatic cancer.     

Cyclophosphamide augments the anti-tumor efficacy of uracil and tegafur by inhibiting dihydropyrimidine dehydrogenase

The present study assesses the effects of neo-adjuvant chemotherapy (NAC) with uracil and tegafur (UFT) alone vs UFT plus cyclophosphamide (CPA), on the activity of thymidylate synthase (TS) and dihydropyrimidine dehydrogenase (DPD) in breast cancer tissues. Breast cancer patients were randomly assigned to 3 groups; the control (no-treatment) group (n=13), the UFT (5-8 mg/kg/day) alone group (n=10) and the UFT plus CPA (1 mg/kg/one day interval) (UC) group (n=9), and they received NAC for 2-4 weeks. A total of 32 invasive ductal breast carcinomas were used to assay for TS and DPD activity. There were no statistically significant differences in tumor size or stage classification between the 3 groups. The DPD activity was inversely and significantly correlated with the tumor size and pT, but the TS activity was not correlated with these clinicopathological factors. The TS activity was decreased by NAC with UFT, and the addition of CPA resulted in an increased inhibition of TS activity. In contrast, DPD activity was increased by NAC with UFT administration, but its increased activity was significantly inhibited by the addition of CPA. Multiple regression analyses demonstrated that the total dose of UFT was a significant variable for inhibiting TS activity, and that CPA was a significant variable for inhibiting DPD activity. The DPD activity increased by UFT can be inhibited by CPA, and this may represent one of the possible mechanisms responsible for the anti-tumor activity of 5-FU or its derivatives as enhanced by CPA.     

Carboplatin and tegafur-uracil concomitant with standard radiotherapy in the management of locally advanced head and neck cancer

INTRODUCTION: We undertook a prospective study to determine the feasibility, toxicity, response and survival rate of simultaneous chemotherapy (CT) and radiotherapy (RT) for locally-advanced head and neck cancer. MATERIAL AND METHODS: Fifty eight patients were treated with carboplatin (i.e. 100 mg/m(2)) weekly, tegafur-uracil (UFT) (oral 400 mg/m(2)) daily and simultaneous treatment with a cobalt-60 source of radiation (total dose 65-70 Gy). RESULTS: Forty six patients (79%) received the total dose of RT while CT was delayed or reduced in 31 patients (53%). Grade 3-4 toxicity observed was mucositis in 27 (47%), leukopenia in 10 (17%), anaemia in 5 (9%), and diarrhoea in 4 (7%) patients. The objective response rate was 74%; 24 complete response (41%) and 19 partial response (33%). Overall, there are 11 patients (19%) disease-free, 7 (12%) alive with disease, 35 have died of progressive disease (60%) and 3 (5%) from other causes. There were 2 toxic deaths (3%). Median time to progression was 10 months and median survival was 18.4 months. CONCLUSIONS: The use of carboplatin and UFT concomitant with radiotherapy has, in our study, a slightly lower activity than other chemo-radiotherapy protocols, especially with respect to complete responses, but with no significant differences in overall survival or disease-free survival rates.     

Preoperative uracil, tegafur, and concomitant radiotherapy in operable rectal cancer: a phase II multicenter study with 3 years' follow-Up.

PURPOSE: To assess tolerance and efficacy of preoperative treatment with uracil/tegafur and radiotherapy (RT) followed by surgery and postoperative flurouracil (FU)/leucovorin (LV) in patients with rectal cancer. PATIENTS AND METHODS: Patients (n = 94) with potentially resectable tumors, ultrasound at stages T2N+ (n = 4), T3 (n = 77), T4 (n = 13) were treated with UFT (400 mg/m2/d, 5 days a week for 5 weeks) and concomitant RT to the pelvis (45 Gy; 1.8 Gy/d over 5 weeks). Patients underwent surgery 5 to 6 weeks later followed by four cycles of FU/LV. Primary end points included downstaging, pathologic responses, and sphincter-preserving surgery. Secondary end points were recurrence-free survival and overall survival. RESULTS: All patients received the full RT dose. Fifteen patients (16%) needed UFT dose reduction. Preoperative G3+ toxicities included diarrhea (14%), leukopenia (1%), thrombocytopenia (1%), and nausea (4%). The downstaging rate was 54%, pathologic complete response (pCR) was 9% and, in an additional 23%, there were only residual microscopic foci. When cellular viability criteria were taken into account, the pCR was 15%. From 43 patients with abdominoperineal resection indication, 11 (25%) had sphincter-preserving surgery performed. Postoperative scheduled chemotherapy dose was not administered to 24% of patients because of G3+ toxicity (diarrhea, 8%; mucositis, 9%; and leukopenia, 7%). Patients with downstaging had significantly higher survival and recurrence-free survival rates than those without. At 3 years, actuarial patterns of failure were pelvic, 5% and distant, 11%. OS was 75%. CONCLUSION: UFT combined with RT is safe and effective. In resectable rectal cancer, if preoperative treatment is considered, this approach can be an option.     

Docetaxel (Taxotere), cisplatin, UFT, and leucovorin combination chemotherapy in advanced gastric cancer

We conducted this study to ascertain the efficacy and toxicity of docetaxel and cisplatin combined with oral UFT and leucovorin as a first-line treatment for patients with advanced gastric cancer. In all, 52 patients received courses of docetaxel 60 mg m(-2) intravenously (i.v.) for 1 h and then cisplatin 75 mg m(-2) i.v. for 2 h on day 1. Oral UFT at 400-600 mg day(-1), as determined by body surface area, and leucovorin at 75 mg day(-1) were administered for 21 consecutive days from day 1, and this was followed by a 7-day drug-free interval. A total of 225 courses were administered, and the median number of courses per patient was four. Four complete responses (7.7%) and 22 partial responses (42.3%) were achieved, giving an overall response rate of 50% (95% Confidence Interval: 36.4-63.6%). The major toxicity was neutropenia, which reached grade 3/4 in 36 patients (69.3%). Grade 3/4 nausea and vomiting was observed in 12 patients (23.1%). Median time to progression was 22 weeks (4 to 156+ weeks), median survival duration was 48 weeks (4 to 156+ weeks), and median response duration was 24 weeks (6-152 weeks). We conclude that docetaxel, cisplatin, oral UFT, and leucovorin combination chemotherapy is effective and tolerable for the treatment of advanced gastric cancer.     

Combination chemotherapy with UFT, etoposide, CDDP, adriamycin (FEPA) in advanced gastric cancer

Fifteen patients with inoperable advanced gastric cancer were treated with UFT.etoposide.CDDP.adriamycin (FEPA). Six were males and 9 were females with an average age of 58 (range 40 to 80 years). Nine patients were in P.S. 2 and 6 in P.S. 3. FEPA regimen was performed every 4 weeks as follows: UFT 400 mg/m2 (p.o.) every day, etoposide 50 mg/m2 (i.v.), CDDP 25 mg/m2 (i.v.) and adriamycin 10 mg/m2 (i.v.) on days 1, 8, 15 and 22. Among 15 patients, 6 partial remissions and 4 minor responses were obtained. Gastrectomy was performed in 2 of 6 PR patients after FEPA chemotherapy. The overall response rate was 40.0%. As for side effects, mild myelosuppression was the most frequent (66.7%), followed by alopecia and nausea. We concluded that combination chemotherapy of FEPA is useful for inoperable advanced gastric cancer.     

A randomized phase II trial of adjuvant chemotherapy with uracil/tegafur and gemcitabine versus gemcitabine alone in patients with resected pancreatic cancer

BACKGROUND: There have been few randomized studies of adjuvant chemotherapy using gemcitabine (GEM) in patients with resected pancreatic cancer. METHODS: Patients with invasive ductal pancreatic cancer who underwent radical surgery were enrolled and assigned to receive uracil/tegafur (UFT) and GEM together (GU) or GEM alone (G). GEM was administrated at a dosage of 1 g/m(2) intravenously weekly 3 of 4 weeks and UFT at a dosage of 200 mg/day orally continuously. Eligibility included resection status 0 or 1, and no previous chemo- or/and radiation therapy. The primary endpoint was disease-free survival (DFS), and secondary endpoints included overall survival (OS) and toxicity. RESULTS: Between 2002 and 2005, 100 patients were randomized into the 2 arms of the trial (50 patients to GU and 50 to G). One patient in the G group was found to be ineligible. Baseline characteristics were well balanced between the 2 groups. With a median observation period of 21 months, the 1- and 3-year DFS rates were 50.0% and 17.7% in the GU group and 49.0% and 21.6% in the G group, respectively. The median OS was 21.2 months in the GU group and 29.8 months in the G group. Toxicity was minor and acceptable, less than grade 4 in both groups. CONCLUSIONS: Postoperative GEM-based adjuvant chemotherapy was safe and well tolerated. However, addition of UFT with GEM did not improve DFS as compared with GEM alone. Further clinical trial resources for adjuvant chemotherapy should address other combinations and novel agents.     

A case of advanced pancreatic cancer treated with chemoradiation

A 56-year-old man is presented with diarrhea, which he had experienced since February 2004. He was diagnosed as having advanced pancreatic cancer by enhanced abdominal CT scan in May 2004. He was diagnosed with unresectable pancreatic cancer, and treated with a combination of radiation (3 Gy/day) and injections of gemcitabine (GEM) 1,200 mg/week (800 mg/m2, BSA 1.6). Abdominal CT scan revealed a minor response (tumor diameter 5.7 x 4.8 --> 5.2 x 4.4). Accordingly, the improvement of performance status and reduction in serum levels of arcinoembryonic/carbohydrate antigen 19-9 (CA19-9) were observed. In July 2004, chemotherapy and radiotherapy were switched to GEM+UFT (UFT 360 mg/day, a total of 4,320 mg, GEM 1,200 mg according to the body mass, a total of 2,400 mg). The patient's performance state was stable for 6 months but serum levels of CA19-9 increased from March 2005, and he complained of diarrhea and back-pain. Therefore, the combination chemotherapy with GEM and cisplatin (CDDP) was started in April 2005, but there was no clinical effect. GEM and TS-1 are currently being administered. Pancreatic cancer is one of the worst prognoses of any malignant disease. Although the prognosis of unresectable pancreatic cancer is very poor, we presented a case where performance status and survival benefits were obtained by undergoing chemoradiation with GEM and combination chemotherapy with UFT and GEM.     

Clinical usefulness of UFT and cyclophosphamide as salvage chemotherapy for patients with metastatic breast cancer

A combination of UFT and cyclophosphamide (CPA) was orally administered to 12 women with previously-treated advanced or recurrent breast cancer. The daily dose of UFT was 400 to 600 mg for tegafur and 100 mg for CPA. Treatment was given orally for 2 weeks followed by 1 week of no treatment, or for 5 days followed by 2 days of no treatment. The response to treatment was CR in 2 patients, PR in 2, and long NC in 2. The response rate was 33.3%, and the clinical benefit 50%. Adverse reactions comprised grade 3 diarrhea requiring admission in 1 patient, over grade 1 leukopenia in 5 patients, and thrombocytopenia in 2 patients. These reactions could be controlled. The combination of UFT and CPA can be given on an outpatient basis and is considered a useful regimen for the management of previously-treated advanced or recurrent breast cancer.