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Corrado Gallo Stampino - One of the best experts on this subject based on the ideXlab platform.
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oral Doxifluridine in advanced hepatocellular carcinoma a phase ii study
Oncology, 2000Co-Authors: M Lencioni, E Pfanner, Alfredo Falcone, G Allegrini, Gianluca Masi, I Brunetti, Roberta Di Marsico, E Fontana, C Orlandini, Corrado Gallo StampinoAbstract:Hepatocellular carcinoma (HCC) remains one of the most common neoplasms in the world. Doxifluridine is an oral fluoropyrimidine derivative activated to 5-fluorouracil by uridine phosphorylase which is more expressed in malignant cells. Therefore, we conducted a phase II study to evaluate the activity of oral Doxifluridine in patients with advanced hepatocellular carcinoma. Twenty-five advanced hepatocellular carcinoma patients entered the study; Doxifluridine was given orally at the initial daily total dose of 2,250 mg for 4 consecutive days every week. All patients are evaluable for toxicity: these included mainly grade 1-2 (WHO) diarrhea, stomatitis, nausea and vomiting; 4 patients (16%) experienced grade 3-4 diarrhea. Twenty-four patients are evaluable for response and 1 complete and 3 partial responses have been observed (response rat 17%, 95% confidence interval: 5-37). Oral Doxifluridine at the dose and schedule we used, although having only modest activity in advanced HCC, may represent an alternative to other frequently used chemotherapeutic agents, because of its favorable toxicity profile and its simple route of administration.
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Oral Doxifluridine in Advanced Hepatocellular Carcinoma: A Phase II Study.
2000Co-Authors: M Lencioni, E Pfanner, Alfredo Falcone, G Allegrini, Gianluca Masi, I Brunetti, Roberta Di Marsico, E Fontana, C Orlandini, Corrado Gallo StampinoAbstract:Hepatocellular carcinoma (HCC) remains one of the most common neoplasms in the world. Doxifluridine is an oral fluoropyrimidine derivative activated to 5-fluorouracil by uridine phosphorylase which is more expressed in malignant cells. Therefore, we conducted a phase II study to evaluate the activity of oral Doxifluridine in patients with advanced hepatocellular carcinoma. Twenty-five advanced hepatocellular carcinoma patients entered the study; Doxifluridine was given orally at the initial daily total dose of 2,250 mg for 4 consecutive days every week. All patients are evaluable for toxicity: these included mainly grade 1-2 (WHO) diarrhea, stomatitis, nausea and vomiting; 4 patients (16%) experienced grade 3-4 diarrhea. Twenty-four patients are evaluable for response and 1 complete and 3 partial responses have been observed (response rat 17%, 95% confidence interval: 5-37). Oral Doxifluridine at the dose and schedule we used, although having only modest activity in advanced HCC, may represent an alternative to other frequently used chemotherapeutic agents, because of its favorable toxicity profile and its simple route of administration. Copyright 2000 S. Karger AG, Basel
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pharmacokinetics of oral Doxifluridine in patients with colorectal cancer
Tumori, 1999Co-Authors: Maria Giulia Zampino, Corrado Gallo Stampino, Marco Colleoni, E Bajetta, Alberto Guenzi, Filippo De BraudAbstract:AIMS AND BACKGROUND Doxifluridine is a new fluoropyrimidine that has excellent absorption by the gastrointestinal tract when given orally. The aim of the study was to determine the disposition of Doxifluridine and fluorouracil when the former is given orally for 5 days and to assess whether their pharmacokinetics are influenced by demographic or biologic parameters. METHODS AND STUDY DESIGN Twenty colorectal cancer patients received levo-leucovorin, 25 mg orally on days 1-5, followed 2 hrs later by Doxifluridine, 1200 mg/m2; the cycle was repeated every 10 days. Doxifluridine and fluorouracil levels were measured by reverse-phase high-performance liquid chromatography during the first cycle of therapy. The lowest dose given over the first 24 hrs was 1750 mg and the highest was 2500 mg. RESULTS The distribution of Doxifluridine parameters remained the same between days 1 and 5, with an AUC that ranged between 72.2 and 74.5 mmol h/l and a C max that remained in a narrow band of 67.1 to 68.3 mmol/l. In contrast, the variability of fluorouracil parameters increased from day 1 to day 5, with an AUC of respectively 5.46 and 7.52 mmol h/l and a C max that increased from 5.81 on day 1 to 7.34 mmol/l on day 5. A significant correlation between the AUC of Doxifluridine and fluorouracil was found on day 1 and on day 5 (P < 0.001). None of the demographic or biologic parameters considered was significantly related to pharmacokinetic parameters. Fluorouracil levels remained low in comparison with levels measured after classical fluorouracil therapy, although detectable for a longer time. CONCLUSIONS A large interpatient pharmacokinetic variability was observed without any significant correlation with the clinical parameters studied.
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phase ii study of oral Doxifluridine in elderly patients with advanced non small cell lung cancer
American Journal of Clinical Oncology, 1996Co-Authors: Elizabeth H Baldini, Corrado Gallo Stampino, C Tibaldi, E Pfanner, Sergio Ricci, Alfredo Falcone, A Ceribelli, R Sarcina, G Comella, Pierfranco ConteAbstract:Elderly patients with advanced non-small-cell lung cancer (NSCLC) are usually excluded from most clinical trials because of the toxicity associated with chemotherapy. About 50% of the new cases of lung cancer occur in patients older than 65 years. Doxifluridine is a fluoropyrimidine derivate which can be administered orally with very low toxicities. This phase II study evaluates the toxicity and activity of a home therapy with oral Doxifluridine in elderly advanced NSCLC patients. Thirty-three advanced NSCLC patients, aged 70 years or more, entered the study; median ECOG performance status was 1 (0-2) and 22 patients (66.6%) had metastatic disease. Doxifluridine was given orally in three divided doses, for a total daily dose of 2,250 mg, for 4 consecutive days every week. The treatment was well tolerated; five patients (15%) experienced a grade 3 diarrhea which required Doxifluridine dose reduction to 1,500 mg daily. Thirty-one patients are evaluable for response; four partial responses (12.9%) have been observed (95% confidence limit interval 3.6-29.8%); 17 patients (54.8%) had a stabilization of the disease. This study demonstrates that a home therapy with oral Doxifluridine in elderly NSCLC patients is feasible and well tolerated and should encourage further studies.
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Doxifluridine as palliative treatment in advanced gastric and pancreatic cancer patients
Oncology, 1996Co-Authors: Maria Di Bartolomeo, Corrado Gallo Stampino, E Bajetta, L Somma, C Carnaghi, Elena Bandieri, Michele Del Vecchio, Roberto BuzzoniAbstract:Background : The association of 5-fluorouracil (5-FU) and leucovorin is currently the most used combination in the treatment of advanced gastrointestinal neoplasms. Doxifluridine (d-
H Furukawa - One of the best experts on this subject based on the ideXlab platform.
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multi center phase ii study for combination therapy with paclitaxel Doxifluridine to treat advanced recurrent gastric cancer showing resistance to s 1 ogsg 0302
Japanese Journal of Clinical Oncology, 2008Co-Authors: Hiroya Takiuchi, Hiroshi Imamura, Motohiro Imano, Yutaka Kimura, H Furukawa, Hideyuki Ishida, Masahiro Goto, Haruhiko Imamoto, K Fujitani, Hiroyuki NaraharaAbstract:Background 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. Methods 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. Results 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. Conclusions The combination of paclitaxel and Doxifluridine might be a treatment of choice as a second line chemotherapy for patient undergone S-1 treatment.
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multi center phase ii study for combination therapy with paclitaxel Doxifluridine to treat advanced recurrent gastric cancer showing resistance to s 1 final results ogsg 0302
Journal of Clinical Oncology, 2007Co-Authors: Hiroya Takiuchi, Toshimasa Tsujinaka, Hiroshi Imamura, Motohiro Imano, Yutaka Kimura, Hiroo Ishida, Y Nakane, Hiroyuki Narahara, S Morimoto, H FurukawaAbstract:15025 Background: We report here results of phase II study for a combination therapy with paclitaxel/Doxifluridine to treat advanced/recurrent gastric cancer showing resistance to S-1. S-1 is an or...
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Multi-Center Phase II Study for Combination Therapy with Paclitaxel/Doxifluridine to Treat Advanced/Recurrent Gastric Cancer Showing Resistance to S-1 (OGSG 0302)
2007Co-Authors: Hiroya Takiuchi, Hiroshi Imamura, Motohiro Imano, Yutaka Kimura, H Furukawa, Hideyuki Ishida, Masahiro Goto, Haruhiko Imamoto, K Fujitani, Hiroyuki NaraharaAbstract:Background: A pre-clinical study demonstrated that paclitaxel induced thymidine phosphoryl-ase 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 unre-sectable or recurrent gastric cancer who had been previously treated with S-1. Methods: Registration was started to enroll 35 patients with advanced/recurrent gastric cancer, who were selected among those with measurable lesions fitting to response evalu-ation criteria in solid tumors, and with resistant to S-1 treatment. This regimen is consisted of paclitaxel, 80 mg/m2, iv on days 1 and 8; and Doxifluridine, 600 mg/m2, 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. Results: 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
Hiroya Takiuchi - One of the best experts on this subject based on the ideXlab platform.
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multi center phase ii study for combination therapy with paclitaxel Doxifluridine to treat advanced recurrent gastric cancer showing resistance to s 1 ogsg 0302
Japanese Journal of Clinical Oncology, 2008Co-Authors: Hiroya Takiuchi, Hiroshi Imamura, Motohiro Imano, Yutaka Kimura, H Furukawa, Hideyuki Ishida, Masahiro Goto, Haruhiko Imamoto, K Fujitani, Hiroyuki NaraharaAbstract:Background 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. Methods 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. Results 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. Conclusions The combination of paclitaxel and Doxifluridine might be a treatment of choice as a second line chemotherapy for patient undergone S-1 treatment.
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multi center phase ii study for combination therapy with paclitaxel Doxifluridine to treat advanced recurrent gastric cancer showing resistance to s 1 final results ogsg 0302
Journal of Clinical Oncology, 2007Co-Authors: Hiroya Takiuchi, Toshimasa Tsujinaka, Hiroshi Imamura, Motohiro Imano, Yutaka Kimura, Hiroo Ishida, Y Nakane, Hiroyuki Narahara, S Morimoto, H FurukawaAbstract:15025 Background: We report here results of phase II study for a combination therapy with paclitaxel/Doxifluridine to treat advanced/recurrent gastric cancer showing resistance to S-1. S-1 is an or...
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Multi-Center Phase II Study for Combination Therapy with Paclitaxel/Doxifluridine to Treat Advanced/Recurrent Gastric Cancer Showing Resistance to S-1 (OGSG 0302)
2007Co-Authors: Hiroya Takiuchi, Hiroshi Imamura, Motohiro Imano, Yutaka Kimura, H Furukawa, Hideyuki Ishida, Masahiro Goto, Haruhiko Imamoto, K Fujitani, Hiroyuki NaraharaAbstract:Background: A pre-clinical study demonstrated that paclitaxel induced thymidine phosphoryl-ase 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 unre-sectable or recurrent gastric cancer who had been previously treated with S-1. Methods: Registration was started to enroll 35 patients with advanced/recurrent gastric cancer, who were selected among those with measurable lesions fitting to response evalu-ation criteria in solid tumors, and with resistant to S-1 treatment. This regimen is consisted of paclitaxel, 80 mg/m2, iv on days 1 and 8; and Doxifluridine, 600 mg/m2, 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. Results: 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
Hiroyuki Narahara - One of the best experts on this subject based on the ideXlab platform.
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multi center phase ii study for combination therapy with paclitaxel Doxifluridine to treat advanced recurrent gastric cancer showing resistance to s 1 ogsg 0302
Japanese Journal of Clinical Oncology, 2008Co-Authors: Hiroya Takiuchi, Hiroshi Imamura, Motohiro Imano, Yutaka Kimura, H Furukawa, Hideyuki Ishida, Masahiro Goto, Haruhiko Imamoto, K Fujitani, Hiroyuki NaraharaAbstract:Background 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. Methods 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. Results 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. Conclusions The combination of paclitaxel and Doxifluridine might be a treatment of choice as a second line chemotherapy for patient undergone S-1 treatment.
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multi center phase ii study for combination therapy with paclitaxel Doxifluridine to treat advanced recurrent gastric cancer showing resistance to s 1 final results ogsg 0302
Journal of Clinical Oncology, 2007Co-Authors: Hiroya Takiuchi, Toshimasa Tsujinaka, Hiroshi Imamura, Motohiro Imano, Yutaka Kimura, Hiroo Ishida, Y Nakane, Hiroyuki Narahara, S Morimoto, H FurukawaAbstract:15025 Background: We report here results of phase II study for a combination therapy with paclitaxel/Doxifluridine to treat advanced/recurrent gastric cancer showing resistance to S-1. S-1 is an or...
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Multi-Center Phase II Study for Combination Therapy with Paclitaxel/Doxifluridine to Treat Advanced/Recurrent Gastric Cancer Showing Resistance to S-1 (OGSG 0302)
2007Co-Authors: Hiroya Takiuchi, Hiroshi Imamura, Motohiro Imano, Yutaka Kimura, H Furukawa, Hideyuki Ishida, Masahiro Goto, Haruhiko Imamoto, K Fujitani, Hiroyuki NaraharaAbstract:Background: A pre-clinical study demonstrated that paclitaxel induced thymidine phosphoryl-ase 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 unre-sectable or recurrent gastric cancer who had been previously treated with S-1. Methods: Registration was started to enroll 35 patients with advanced/recurrent gastric cancer, who were selected among those with measurable lesions fitting to response evalu-ation criteria in solid tumors, and with resistant to S-1 treatment. This regimen is consisted of paclitaxel, 80 mg/m2, iv on days 1 and 8; and Doxifluridine, 600 mg/m2, 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. Results: 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
Maria Grano - One of the best experts on this subject based on the ideXlab platform.
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in vitro toxicity of n3 methyl 5 deoxy 5 fluorouridine a novel metabolite of Doxifluridine a bioanalytical investigation
Journal of Pharmaceutical and Biomedical Analysis, 1998Co-Authors: Carlo G. Zambonin, Antonella Aresta, Maria GranoAbstract:Abstract The cytotoxicity of N 3 -methyl-5′-deoxy-5-fluorouridine ( N 3 -Me-5′-dFUR), a novel metabolite of the anticancer pro-drug 5′-deoxy-5-fluorouridine (5′-dFUR), has been evaluated by in vitro experiments with cultures of different cancer cell lines. The new metabolic product was found to be non-toxic in all the cell growth experiments performed. The absence of cytotoxicity could be explained by the observation that the metabolite was not recognized as a substrate by thymidine phosphorilase, the enzyme responsible for 5-fluorouracil (5-FU) release from Doxifluridine, as ascertained by high-performance liquid chromatography/ultraviolet (HPLC–UV) analysis of the incubation mixture. The biomethylation process leading to N 3 -Me-5′-dFUR could be considered as a possible detoxification pathway, altering the drug bioavailability, in competition with 5′-dFUR cleavage to the active 5-FU.
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In vitro toxicity of N3-methyl-5′-deoxy-5-fluorouridine, a novel metabolite of Doxifluridine: a bioanalytical investigation
Journal of pharmaceutical and biomedical analysis, 1998Co-Authors: Carlo G. Zambonin, Antonella Aresta, Maria GranoAbstract:Abstract The cytotoxicity of N 3 -methyl-5′-deoxy-5-fluorouridine ( N 3 -Me-5′-dFUR), a novel metabolite of the anticancer pro-drug 5′-deoxy-5-fluorouridine (5′-dFUR), has been evaluated by in vitro experiments with cultures of different cancer cell lines. The new metabolic product was found to be non-toxic in all the cell growth experiments performed. The absence of cytotoxicity could be explained by the observation that the metabolite was not recognized as a substrate by thymidine phosphorilase, the enzyme responsible for 5-fluorouracil (5-FU) release from Doxifluridine, as ascertained by high-performance liquid chromatography/ultraviolet (HPLC–UV) analysis of the incubation mixture. The biomethylation process leading to N 3 -Me-5′-dFUR could be considered as a possible detoxification pathway, altering the drug bioavailability, in competition with 5′-dFUR cleavage to the active 5-FU.