Disease relevance of Trifosfamide

• In relapsed 'adult type' soft tissue sarcomas, trofosfamide, gemcitabine and trabectedin (ecteinascidin 743) appear to be drugs associated with some activity and an acceptable toxicity profile [1].
• Trofosfamide as a salvage treatment with low toxicity in malignant lymphoma. A phase II study [2].
• Treatment of paediatric pontine glioma with oral trophosphamide and etoposide [3].
• Trofosfamide is effective in refractory non-Hodgkin's lymphoma [4].
• 37 patients with disease progression after prior treatment for malignant lymphoma (27 low grade, 7 high grade and 3 Hodgkin's) were treated with oral trofosfamide daily [2].

High impact information on Trifosfamide

• Pharmacokinetics and efficacy of ifosfamide or trofosfamide in patients with intraocular lymphoma [5].
• Cyclophosphamide, ifosfamide, trofosfamide and two secondary metabolites show a weak activity in vitro (Inhibitory Dose--50% (ID50) between 5 X 10(-4) M and 5 X 10(-5) M) [6].
• After in vivo treatment, cyclophosphamide, ifosfamide and trofosfamide induce an important decrease of nucleated bone marrow cells [6].
• The aim of this study was to develop and validate a novel solid-phase extraction (SPE) liquid chromatography/tandem mass spectrometry (LC/MS/MS) method for the simultaneous determination of two antineoplastic drugs, cyclophosphamide (CP) and methotrexate (MTX), in human urine using trophosphamide as internal standard [7].
• Metronomic trofosfamide inhibits progression of human lung cancer xenografts by exerting anti-angiogenic effects [8].

Chemical compound and disease context of Trifosfamide

• Urotoxic side effects, especially hemorrhagic cystitis, have so far been a limiting factor in the therapeutic use of cyclophosphamide (Endoxan), ifosfamide (Holoxan), and trofosfamide (Ixoten) [9].
• A few studies have shown that trofosfamide, an oral alkylating agent, may be effective as palliative treatment in non-Hodgkin's lymphoma [10].
• Phase II trial of continuous oral trofosfamide in patients with advanced colorectal cancer refractory to 5-fluorouracil [11].
• PATIENTS AND METHODS: Twenty patients suffering from advanced prostate cancer were treated with per os trofosfamide after progression on androgen ablation and/or estramustine [12].
• We present three cases with chylothorax due to malignant non-Hodgkin's lymphoma [high grade malignant (1 case) and low grade malignant (2 cases)] treated with pleurodesis with bleomycin and systemic chemotherapy (CHOP, CNOP, trofosfamide) [13].

Biological context of Trifosfamide

• Flow cytometric assessment of trophosphamide toxicity on mouse spermatogenesis [14].
• Investigations on the pharmacokinetics of trofosfamide and its metabolites-first report of 4-hydroxy-trofosfamide kinetics in humans [15].
• In vivo LX-1 xenotransplanted nude mice were treated with trofosfamide in conventional and metronomic schedules (i.p./p.o.). Tumor sections were evaluated for microvessel density (MVD), relative growth fraction and apoptosis [8].
• In order to estimate the occupational exposure of hospital personnel handling these drugs, wipe samples were taken from the working surfaces and directly analyzed (with trophosphamide as internal standard) using a reversed-phase capillary column and MS/MS detection [16].
• Genotoxicity of trophosphamide in mouse germ cells: assessment of micronuclei in spermatids and chromosome aberrations in one-cell zygotes [17].

Anatomical context of Trifosfamide

• Trophosphamide induced dominant lethal and specific-locus mutations in spermatozoa and spermatids of mice [18].
• The spermatogenic specificity of ifosfamide in mouse germ cells is similar to that of the structurally related cytostatic drugs cyclophosphamide and trofosfamide [19].
• In this study, metronomic and conventional trofosfamide were compared on human NSCLC xenograft "LX-1." MATERIALS AND METHODS: In vitro cytotoxicity of trofosfamide on tumor and human umbilical cord endothelial cells was determined under normoxic and hypoxic conditions [8].
• This was confirmed by the observation that only the CYP3A4 contents of five samples of human liver microsomes correlated with both pathways of trofosfamide [20].
• We report herein a case of a 83-year-old female patient with a disseminated malignant peripheral nerve sheath tumor treated with trofosfamide developing pulmonal toxicity [21].

Associations of Trifosfamide with other chemical compounds

• The present study indicates that human liver microsomal CYP3A4 preferentially catalyzes the two NADPH- dependent metabolic routes of trofosfamide, which emphasizes the necessity for awareness of potential interactions with any coadministered drugs that are CYP3A4 substrates [20].
• CONCLUSIONS: This new triple combination of low-dose metronomic trofosfamide, pioglitazone, and rofecoxib may represent a feasible new alternative in the palliative treatment of patients with advanced malignant vascular tumors [22].
• Trofosfamide (Ixoten; Baxter Oncology, Germany) is an alkylating agent that, as with other oxazaphosphorine derivatives, has to be activated by hepatic cytochrome P450 oxidases [21].

Gene context of Trifosfamide

• Enzyme kinetic analyses revealed the dominant role of human CYP3A4 in 4-hydroxylation and N-dechloroethylation of trofosfamide [20].
• Investigation of the major human hepatic cytochrome P450 involved in 4-hydroxylation and N-dechloroethylation of trofosfamide [20].
• Recombinant human CYP3A4 and CYP2B6 exhibited catalytic activity with respect to both pathways of trofosfamide [20].
• A high-performance liquid chromatography chiral stationary phase (HPLC-CSP) based upon cellulose-tris(3,5-dimethylphenylcarbamate), the OD-CSP, was used to stereochemically resolve three racemic anticancer drugs: ifosfamide (IFF), cyclophosphamide (CTX) and trofosfamide (TFF) [23].
• Median survival was 17.1 months in the IFN-alpha-retinoic acid arm, 12.4 months in the trophosphamide arm and 13.5 months in the control arm [24].

Analytical, diagnostic and therapeutic context of Trifosfamide

• Trofosfamide is an interesting and a non-toxic palliative treatment for relapsing malignant lymphomas especially in elderly patients [2].
• To contribute to effective and safe outpatient treatment, we investigated the metabolism of trofosfamide (Trofo) after oral administration [25].
• Adjuvant treatment consisted of oral chemotherapy with trofosfamide, 100 mg/m(2), and etoposide, 25 mg/m(2), daily or for 21-day cycles interrupted by 1-week rests [26].
• Thus, in this particular case, trofosfamide turned out to be an unexpectedly effective salvage therapy for an otherwise very aggressive relapsing ALCL [10].
• A case of a malignant childhood glioma is reported with tumor-progression after surgery and radiotherapy during chemotherapy with cisplatinum, vincristine and CCNU, that responded temporally to oral treatment with VP16 and trofosfamide [27].

References