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At least 19 recordsLinked to original sources
PubMed1977

Chemoimmunotherapy of metastatic large bowel cancer: nonspecific stimulation with BCG and levamisole.

The administration of two chemoimmunotherapy programs to 103 consecutive patients with metastatic colorectal cancer resulted in improved survival for patients who achieved either objective tumor regressions or disease stabilization for more than 8 weeks. Objective tumor regression was observed in 47% of patients treated with the Ftorafur-methyl-CCNU-methotrexate-Bacillus Calmette-Guerin (FTOR-MeM-BCG) program and in 34% of patients treated with the 5-fluorouracil-methotrexate-Baker's antifol (FU-M-BAF) +/- Levamisole program. The combinated median duration of survival for patients who achieved objective tumor regression and disease stabilization with FTOR-MeM-BCG was 13 months compared with 6 months for patients who had progression of disease (p = 0.001). The corresponding values for patients treated with FU-M-BAF +/- levamisole were 11 months and seven months, respectively (p = 0.001). While the role of BCG immunotherapy in these results remains speculative, the administration of levamisole immunotherapy did not appear to have influenced results significantly. Patients who presented at diagnosis with Dukes A, B and C lesions, and therefore had longer disease-free intervals, responded more frequently to chemoimmunotherapy and survived longer than patients who presented at diagnosis with Dukes D lesions. Similarly, greater antitumor effect was observed in patients with lower pretreatment plasma CEA levels evaluation of these pretreatment characteristics may have insignificant implications for the design of future clinical trials.

BCG Vaccine↗
PubMed1979

Phase II evaluation of ftorafur in previously untreated colorectal cancer: a Southwest Oncology Group Study.

Eighty-four previously untreated patients with metastatic adenocarcinoma of the large intestine received intravenous ftorafur at a dosage of 2.25 g/m2/day for 5 consecutive days. Courses were repeated every three weeks. Regressions were noted in 9 of 84 treated patients (11%). Median survival for all patients was 32 weeks. Responders survived only 5 weeks longer than nonresponders; 36 vs. 31 weeks. Central nervous system toxicity was a limiting factor occurring in one-third of patients. Ftorafur in a daily X5 schedule appears not to make a significant contribution to the management of disseminated colorectal cancer.

Adenocarcinoma↗
PubMed1979

Ftorafur, adriamycin, cyclophosphamide and BCG in the treatment of metastatic breast cancer.

Ftorafur is a 5-fluorouracil analogue which is slowly metabolized to 5-FU, resulting in prolonged therapeutic levels of this latter drug. Ninety-one evaluable patients with metastatic breast cancer were treated with Ftorafur, Adriamycin, cyclophosphamide, and BCG (ACFTOR-BCG), in an attempt to increase the effectiveness of the program or decrease its myelosuppressive toxicity. The results of this trial were compared to those previously reported with the combination of 5-FU, Adriamycin, cyclophosphamide, and BCG (FAC-BCG). Overall objective response rates were 65% and 76% for ACFTOR-BCG and FAC-BCG, respectively. Durations of response were 12 months and 14 months for ACFTOR-BCG and FAC-BCG (p = 0.53). The median survival of responders was 22 and 23.9 months, respectively. Substantial toxicity was observed with Ftorafur: nausea and vomiting severe enough to cause weight loss was observed in a substantially higher fraction of the patients treated with this drug than with 5-FU. Other side-effects, which were not observed with the 5-FU combination, were somnolence, dizziness, personality changes, tremor, ataxia, and confusion. No differences in myelosuppressive toxicity were observed between the two combinations, and the incidence of infectious complications was identical. The combination of Ftorafur, Adriamycin, cyclophosphamide and BCG did not offer any advantages with respect to increased effectiveness or reduced toxicity over the FAC-BCG regimen in breast carcinoma.

Adult↗
PubMed1979

Phase I-II study of ftorafur and methyl-CCNU in advanced colorectal cancer.

The combination of Ftorafur (NSC-148958) and methyl-CCNU (NSC-95441) was evaluated in 36 patients with advanced colorectal cancer. The principle toxicities encountered were myelosuppression, gastrointestinal, and neurological. There were no complete responses and only 5/34 (14.7%) patients achieved a partial response. Methyl-CCNU and Ftorafur does not appear to be an effective combination in advanced adenocarcinoma of the colon and rectum.

Adenocarcinoma↗
PubMed1979

A phase II trial of ftorafur: adriamycin and mitomycin-C (FAM II) in advanced gastric adenocarcinoma.

Fifteen patients with advanced gastric cancer were treated with the combination of Ftorafur, Adriamycin and mitomycin-C (FAM II). Three patients showed partial responses, in five the disease remained stable for at least 3 months and seven showed progression while on treatment. All responding patients showed survival in excess of 12 months. Hematologic toxicity was of only moderate severity. Median white count nadir was 3500 cells/mm3 and median platelet nadir was 187,000 cells/mm3. Four patients had white count nadirs from 2000--2500 cells/mm3 and three had nadirs from 500--1500 cells/mm3; also there were four with platelet nadirs less than 100,000/mm3. However, no drug-related infections occurred and no platelet transfusions were required. The major non-hematologic toxicities of the regimen were nausea, vomiting, dizziness, vertigo, and rhinorrhea. These toxicities were limiting and resulted in termination of the trial because of poor patient acceptance and the failure of the combination to exhibit a therapeutic advantage over the similar combination (FAM) that employed weekly 5-fluorouracil in place of Ftorafur.

Adenocarcinoma↗
PubMed1979

Adriamycin, BCNU, ftorafur chemotherapy of pancreatic and biliary tract cancer.

Twenty-six evaluable patients with disseminated or locally unresectable pancreatic or biliary tract carcinoma received Ftorafur (4 g/m2 iv day 1 and 22 and 2 g/m2 iv day 4 and 26), Adriamycin (60 mg/m1 IV day 1 and 45 mg/m2 iv day 22) and BCNU (150 MG/M2 IV DAY 1) combination chemotherapy (FAB) repeated at 6--8 week intervals. Two (29%) complete and one (14%) partial remissions were observed in 7 patients with biliary carcinoma while 5 of 19 (26%) patients with pancreatic carcinoma achieved partial remissions. Median survival for responding patients was approximately 11 months (range 7--16+) with median survivals of about 6 months (p less than 0.05 and about 3 months (p less than 0.05) for patients with stable and progressive disease. Major drug toxicity was myelosuppression with median lowest granulocyte counts of 1,000/microliters and platelet counts of 88,000/microliters. Approximately 25% of patients required antibiotic therapy for fever of unknown origin or documented infections. Other tolerable drug toxicities included nausea, vomiting and mucositis. The FAB regimen appears quite promising in biliary tract cancer and has efficacy in pancreatic carcinoma that warrants further clinical trials. Because of myelotoxicity observed with this regimen we now recommend a BCNU starting dose of 100 mg/m2 instead of 150 mg/m2.

Adult↗
PubMed1977

GLC determination for ftorafur in biological fluids.

A GLC analysis for free ftorafur was developed to follow in drug disposition in body fluids of patients. The free drug was extracted from aqueous biological samples with chloroform, derivatized by methylation, and chromatographed on 1% HI-EFF 8BP using flame-ionization detection. The analysis is sensitive (0.25 microgram/ml of plasma) and specific for the intact molecule, and it does not interfere with subsequent fluorouracil analysis of the same sample.

Chromatography, Gas↗
PubMed1979

Chemoimmunotherapy with or without oophorectomy in premenopausal patients with advanced breast cancer.

Ninety-eight premenopausal patients with stage IV breast cancer were treated with chemoimmunotherapy alone, or with combination oophorectomy-chemoimmunotherapy either simultaneously (chemoimmunotherapy within four weeks of oophorectomy) or sequentially (delayed chemoimmunotherapy until evidence of progressive disease or no response to oophorectomy). The chemoimmunotherapy consisted of a three-drug combination of Adriamycin, cyclophosphamide, and 5-fluorouracil or Ftorafur; immunotherapy consisted of either oral levamisole, BCG by scarification, or a combination of both. Forty patients underwent simultaneous oophorectomy-chemoimmunotherapy, with a response rate of 85% and a median duration of response of 25 months. Response rate of 69% and a median duration of response of 16.6 months was observed with the 29 patients who received sequential oophorectomy-chemoimmunotherapy. Another 29 patients were treated with chemoimmunotherapy alone and achieved a response rate of 87% and a median duration of response of 11.8 months. Though there were no significant differences in the response rate, patients treated with chemoimmunotherapy alone had a significantly shorter median duration of response (P less than 0.05). This would suggest that oophorectomy in combination with chemoimmunotherapy is the most favorable treatment modality for premenopausal patients with advanced metastatic breast cancer.

BCG Vaccine↗
PubMed1979

Immunobiology and therapeutic manipulation of heterotransplanted Nb rat prostatic adenocarcinoma. Chemotherapy of autonomous tumor, 102 Pr, heterotransplanted into congenitally athymic (nude) mice and syngeneic Nb rats.

Nb rat prostatic adenocarcinomas, previously induced by the administration of testosterone and estrogen, have been serially studied as heterotransplants into congenitally athymic (nude) mice and into groups of Nb rats. This animal system has been used to evaluate the chemotherapeutic efficacy of 5-fluorouracil and Ftorafur. The use of both species was to determine if there would be any significant difference in relative tumor growth in nude mice which lack functional T cells as opposed to intact Nb rats. The autonomous tumor, 102 Pr, is the subject of the thesis presented herein. One donor Nb rat bearing 102 Pr prostatic adenocarcinoma served as the donor for this experiment. The nude mice and Nb rats received the transplant on the same date and were subjected to the chemotherapies outlined above and were treated after there was sufficient increase in tumor volume from the 2 mm3 wedge to assure growth and neovascularity (greater than 60 mm3). Statistically significant data was presented revealing 5-fluorouracil to be efficacious in the treatment of these tumors. Also presented is data revealing differences in growth versus time in the respective recipient animal hosts. It is suggested herein that this combination animal model system could be used for screening potential cytotoxic chemotherapeutic agents.

Adenocarcinoma↗
PubMed1979

Post-operative long-term adjuvant immunochemotherapy with mitomycin-C, PSK and FT-207 in gastric cancer patients.

Long-term adjuvant immunochemotherapy carried out on the gastrectomized patients with stomach cancer was reported. The protocol comprises the administration of large-dose of Mitomycin-C (20+10) mg just after gastrectomy and the long-term administration of PSK, FT-207 or (PSK+FT-207). Almost no side effects were observed. According to the studies on the immunological parameters, the increased reactions in PPD skin test and lymphocyte blastogenesis induced by PHA and PWM were observed remarkably in group (P+F) 3 or 6 months after gastrectomy. As for the survival rate, group (P+F) showed the most preferable results at one year in stage IV, at two years in stage III and at three years in all the stages, respectively after gastrectomy.

Adjuvants, Immunologic↗
PubMed2026

Adjuvant oxaliplatin with S-1 (SOX) versus S-1 for stage II-III gastric cancer (CAPITAL): A randomized, open-label, phase 3 trial.

BACKGROUND: Adjuvant chemotherapy following D2 gastrectomy constitutes the standard-of-care for resectable gastric or gastroesophageal junction (GEJ) carcinoma. The CAPITAL trial is a multicenter, randomized, phase 3 study, aiming to assess the efficacy and safety of adjuvant oxaliplatin plus S-1 (SOX) versus S-1 alone. METHODS: Patients with histologically confirmed pathological stage II-III gastric or GEJ adenocarcinoma after gastrectomy with D2 lymphadenectomy were randomly assigned (1:1) to receive either the SOX regimen (n = 362) or the S-1 regimen (n = 362). The primary endpoint was overall survival. This study is registered with ClinicalTrials.gov (NCT01795027). FINDINGS: The median follow-up was 74.0 months (interquartile range [IQR], 35.5-89.3). The 5-year overall survival rates were 70.9% (95% confidence interval [CI], 66.0-76.1) in the SOX group and 62.9% (95% CI, 57.8-68.5) in the S-1 group (hazard ratio [HR], 0.74; 95% CI, 0.58-0.95; p = 0.018). The 3- and 5-year disease-free survival rates were 71.2% (95% CI, 66.5-76.3) and 66.2% (95% CI, 61.2-71.6) in the SOX group, as compared with 65.1% (95% CI, 60.2-70.5) and 55.6% (95% CI, 50.4-61.3) in the S-1 group (HR, 0.76; 95% CI, 0.61-0.96). Treatment-related adverse events of grade 3-4 occurred in 87 (25%) of 349 patients in the SOX group and 45 (13%) of 347 patients in the S-1 group. The most common grade 3-4 adverse event was neutropenia, occurring in 44 (13%) of 349 patients in the SOX group and 23 (7%) of 347 patients in the S-1 group. CONCLUSIONS: The addition of adjuvant oxaliplatin to S-1 chemotherapy significantly improved overall survival and disease-free survival in patients with gastric cancer. FUNDING: This research was supported by the National Natural Science Foundation of China (82573092 and 82573387).

Humans↗
PubMed1979

Synthesis and biological activities of ftorafur metabolites. 3'- and 4'-hydroxyftorafur.

Four isomers of ftorafur were synthesized as authentic samples of possible ftorafur (FT) metabolites. 2,3-Dihydrofuran was treated with perbenzoic acid in MeOH to give 2-methoxy-3-hydroxytetrahydrofuran, which upon treatment with Ac2O/pyridine yielded the key intermediate 2-methoxy-3-acetoxytetrahydrofuran. The other intermediate, 2-ethoxy-4-acetoxytetrahydrofuran, was prepared by acid hydrolysis (HCl/50% EtOH) of 1,1-diethoxy-3,4-dihydroxybutane, followed by acetylation (Ac2O/pyridine). Treatment of 2,4-bis(trimethylsilyl)-5-fluorouracil with either 2-methoxy-3-acetoxytetrahydrofuran or 2-ethoxy-4-acetoxytetrahydrofuran in 1,2-dichloroethane at room temperature using SnCl4 as catalyst afforded cis- and trans-3'-OAc-FT or 4'-OAc-FT, respectively. However, trans-3'-OAc-FT and cis-4'-OAc-FT were the major condensation products. In each case, separation of these cis and trans isomers was achieved by silica gel column chromatography. Treatment of 3'- or 4'-OAc-FT with NH3/CH3OH at 5 degrees C overnight yielded the described hydroxylated FT. Both trans-3'-OH-FT and cis-4'-OH-FT showed no significant activity against L1210 up to 100 mg/kg. These two agents produced an inhibitory effect on HeLa cell growth equal to that of ftorafur, with ID50 = 200 MICROGRAMS/KG.

Animals↗
PubMed1978

Studies on antitumor agents, 2. Syntheses and antitumor activities of 1-(tetrahydro-2-furanyl)-5-fluorouracil and 1,3-bis(tetrahydro-2-furanyl)-5-fluorouracil.

Convenient and efficient methods were developed for preparing 1-(tetrahydro-2-furanyl)-5-fluorouracil (Thf-FU, 3) [trade name, Futraful (Ftorafur) or FT-207], which is used clinically as an antitumor agent, and 1,3-bis(tetrahydro-2-furanyl)-5-fluorouracil (Thf2-FU, 4). For the syntheses, 2,4-bis(trimethylsily)-5-fluorouracil (Me3Si-FU, 1) and 2-acetoxytetrahydrofuran (Thf-OAc, 2) were condensed in the presence of Friedel-Crafts catalysts, such as SnCl4 and BF3-Et2O in dichloromethane, or in the presence of NaI in acetonitrile to give Thf-Fu or Thf2-FU depending on the reaction conditions and workup procedure. A trace of 3-(tetrahydro-2-furanyl)-5-fluorouracil (3-Thf-FU, 5) was formed in these reactions. Thf2-FU was easily hydrolyzed to Thf-FU. 2-Methoxytetrahydrofuran can be used instead of Thf-OAc for preparation of Thf-FU under similar conditions. The optimal ratios of Me3Si-FU, Thf-OAc, and SnCl4 or NaI for preparation of Thf-FU and Thf2-FU were determined. In all cases, 2-2.5 equiv of Thf-OAc with respect to Me3Si-FU gave the best results. The yields of Thf-FU and more especially of Thf2-FU were greatly dependent on the relative amount of SnCl4, and 0.01-0.1 equiv of the catalyst with respect to Me3Si-FU gave the best results. Thf2-FU was found to be effective against murine solid tumors and it was less toxic than Thf-FU when given orally. The antitumor activity of 3-Thf-FU is also reported.

Animals↗