Effects of the new nitrosourea derivative, fotemustine, on the glutathione reductase activity in rat tissues in vivo and in isolated rat hepatocytes

Boutin, Jean A.; Norbeck, Kajsa; Moldéus, Peter; Genton, Annie; Paraire, Marie; Bizzari, Jean-Pierre; Lavielle, Gilbert; Cudennec, Claude A.

doi:10.1016/0277-5379(89)90078-3

Cited by 17 publications

(8 citation statements)

References 16 publications

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“…Overall, FEAM conditioning was well tolerated. Mucositis reached G3/G4 severity in only 30% of cases (median duration 7 days, range [4][5][6][7][8][9][10][11][12][13][14], while G2/G3 chemotherapy-induced nausea and vomiting was documented in 47% of patients, without any G4 episodes. Similarly, 17 and 7% of patients experienced G2 and G3 diarrhea, while no G4 events were observed.…”

Section: Patient Characteristicsmentioning

confidence: 99%

“…11,12 In addition, as FTM does not significantly alter glutathione reductase activity, a more favorable pulmonary toxicity profile for this agent can be predicted compared with BCNU. 13 In fact, several clinical trials have confirmed that FTM, unlike other nitrosoureas, shows no significant pulmonary toxicity. [14][15][16] With regards to antitumor activity, a phase II study by Jacquillat et al, 17 showed that administration of a nonmyeloablative schedule of FTM (100 mg/m 2 on days 1, 8 and 15 (induction), followed after 4-5 weeks by a single 100 mg/m 2 maintenance dose, every 21 days), induced objective clinical responses in 7 of 13 heavily pre-treated patients with hematologic malignancies including HL and NHL; thrombocytopenia was the most commonly observed toxicity.…”

Section: Introductionmentioning

confidence: 95%

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Fotemustine plus etoposide, cytarabine and melphalan (FEAM) as a new conditioning regimen for lymphoma patients undergoing auto-SCT: a multicenter feasibility study

Musso

Scalone

Marcacci

et al. 2009

Bone Marrow Transplant

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Section: Patient Characteristicsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 95%

Fotemustine plus etoposide, cytarabine and melphalan (FEAM) as a new conditioning regimen for lymphoma patients undergoing auto-SCT: a multicenter feasibility study

Musso

Scalone

Marcacci

et al. 2009

Bone Marrow Transplant

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“…This characteristic allows FTM to cross the blood-brain barrier, as demonstrated by experimental studies in animals [60,61]. In addition, as FTM does not significantly alter glutathionereductase activity, a more favorable pulmonary toxicity profile for this agent can be predicted compared with BCNU [62]. In fact, several clinical trials have confirmed that FTM, unlike other nitrosoureas, demonstrates no significant pulmonary toxicity [63][64][65].…”

Section: Fotemustine-based Regimenmentioning

confidence: 92%

Novel Conditioning Regimens for Hodgkin‘S and Non-Hodgkin‘S Lymphoma

Musso

Porretto

Scalone

et al. 2014

Int. J. Hematol. Oncol.

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Autologous stem cell transplantation (ASCT), in chemosensitive relapsed patients with Hodgkin's lymphoma (HL) and non-Hodgkin's lymphoma (NHL), is associated with superior event-free survival (EFS) compared with salvage chemotherapy alone. BEAM is one of the most commonly used regimens in both HL and NHL because of its acceptable toxicity and high effectiveness. The nonrelapsed mortality (NRM) ranges from 7 to 10% in historical studies. More recent investigations have demonstrated a lower NRM, probably due to various factors such as the use of peripheral blood precursor cells and better support therapy. Recently, in order to reduce the toxicity of carmustine and increase antilymphoma activity, several groups have introduced conditioning regimens similar to BEAM. The incorporation of newer drugs (anti-CD20 monoclonal antibodies ± radiolabeled) to 'classic' BEAM, or the substitution of carmustine with other drugs (thiotepa, bendamustine and High-dose chemotherapy (HCT) followed by autologous stem cell transplantation (ASCT) represents a valuable strategy for chemosensitive relapsed patients with Hodgkin's lymphoma (HL) and non-Hodgkin's lymphoma (NHL), and shows superior event-free survival compared with salvage chemotherapy alone.BEAM, which includes carmustine (BCNU), etoposide, cytarabine and melphalan, is one of the most commonly used regimens in both HL and NHL because of its acceptable toxicity and high effectiveness.The nonrelapsed mortality (NRM) of BEAM has been shown to range from 7 to 10% in historical studies. More recent investigations have demonstrated a lower NRM, probably due to various factors such as the use of peripheral blood precursor cells and better support therapy.Recently, in order to reduce the toxicity of BCNU and increase its antilymphoma activity, several study groups have introduced conditioning regimens similar to BEAM.Radioimmunotherapy-based conditionings have a relapse incidence similar to total body irradiation, but with lower toxicity, resulting in improved overall survival.The second-generation BEAM regimens, in which BCNU is substituted with other drugs (i.e., thiotepa, bendamustine and fotemustine), may be a valuable strategy to further reduce toxicity and increase the antilymphoma activity of ASCT.

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“…Compound 134 was found 179 to be inactive against murine cancers which were resistant to BCNU. Various aspects of the metabolism and pharmacokinetics [180][181][182] of 134 were reported. Fotemustine was shown 180 to be a weak inhibitor of glutathione reductase activity from rat e Defined in section V. f Percentage of treated animals surviving on day 45 after tumor implantation.…”

Section: Aliphatic Analogsmentioning

confidence: 99%