Disease relevance of ifosfamide

• Understanding and control of the urinary toxicity of ifosfamide therapy has allowed greater use and inclusion of ifosfamide in combinations in the treatment of malignant diseases [1].
• Between April 1987 and July 1988, 44 adults with histologically proven, objectively assessable advanced nonosseous sarcomas were treated with 2.5 g of ifosfamide/m2, 100 mg of etoposide/m2, and 2.5 g of mesna/m2 (500 mg/m2 X 5) daily for 3 consecutive days every 4 weeks [2].
• Malignant pleural mesothelioma: phase II pilot study of ifosfamide and mesna [3].
• High-dose ifosfamide-induced exacerbation of peripheral neuropathy [4].
• Because of the potential CNS effects of ifosfamide, we recommended that elderly patients, persons receiving high doses of opiates, and patients susceptible to the syndrome of vertigo, perspiration, and hypotension (without tachycardia) be hospitalized for treatment [2].

Psychiatry related information on ifosfamide

• An encephalopathy characterized by confusion, stupor, and mutism frequently occurs during administration of the chemotherapeutic drug ifosfamide (IFX) [5].
• CONCLUSIONS: The present study shows that high-dose continuous-infusion ifosfamide, administered by portable infusion pumps, is feasible in an ambulatory regimen, with acceptable non-haematological toxicity and good patient compliance [6].
• One patient experienced lethargy and confusion that responded to discontinuation of the ifosfamide [7].
• Most cases of ifosfamide-induced hallucinations have been reported with other mental status changes [8].
• Radiologist review versus group peer review of claimed responses in a phase II study on high-dose ifosfamide in advanced soft tissue sarcomas of the adult: a study of the EORTC Soft Tissue and Bone Sarcoma Group [9].

High impact information on ifosfamide

• The patients were randomly assigned to receive either surgery alone or three courses of chemotherapy (6 mg of mitomycin per square meter of body-surface area, 3 g of ifosfamide per square meter, and 50 mg of cisplatin per square meter) given intravenously at three-week intervals and followed by surgery [10].
• While our analysis of osteogenic sarcoma trials is consistent with significant activity for cisplatin and high-dose methotrexate (and likely ifosfamide), a rank ordering of the efficacy of these agents when given with doxorubicin in multiagent regimens is not possible [11].
• We report a phase II study of bleomycin, ifosfamide, and cisplatin (BIP) in cervical cancer [12].
• We did a phase I/II trial in 14 patients with pancreatic cancer to assess the safety of local activation of low-dose ifosfamide [13].
• The median total ifosfamide dose was 100.8 (9.0-160.4) g/m2 over a median of 15 courses every 3 weeks as a 48-72 h continuous intravenous infusion (in 22 cases), with mesna and hydration [14].

Chemical compound and disease context of ifosfamide

• Epidermal growth factor receptors and doxorubicin plus ifosfamide/mesna in recurrent breast cancer [15].
• Prevention of isophosphamide-induced urothelial toxicity with 2-mercaptoethane sulphonate sodium (mesnum) in patients with advanced carcinoma [16].
• INTERVENTIONS: Patients were administered cisplatin (20 mg/m2 body surface area daily for 5 days), ifosfamide (1.2 g daily for 5 days), plus either etoposide (75 mg daily for 5 days) or vinblastine (0.11 mg/kg body weight on days 1 and 2) [17].
• In this study, we used a combination of ifosfamide, methotrexate, and VP-16 to treat 52 patients with lymphoma who had either relapsed or who had failed to attain a complete remission on front-line treatment [18].
• In addition to fractionated cyclophosphamide/ifosfamide, a 24-hour infusion of HD MTX 5 g/m2 in conjunction with an i.th. therapy is an important component for prevention of both systemic and CNS relapses [19].

Biological context of ifosfamide

• Ifosfamide pharmacokinetics and neurotoxicity [20].
• In this phase I study, 29 patients were treated with a 4-day continuous infusion ifosfamide to determine the maximum-tolerated dose and the nonhematologic dose-limiting toxicity [21].
• The severity of hematological toxicity was inversely correlated with glomerular filtration rate but not to parameters of ifosfamide metabolism [22].
• In vivo perturbation of human marrow cell cycle progression by ifosfamide [23].
• Ifosfamide treatment significantly inhibited oxidative phosphorylation with only C-I substrates [24].

Anatomical context of ifosfamide

• CONCLUSIONS: Ifosfamide combination chemotherapy as third-line or greater therapy can produce durable complete remissions in heavily pretreated patients with recurrent germ cell tumors [17].
• PATIENTS: Fifty-two consecutive patients with advanced lymphoma or carcinoma enrolled in phase I trials of high-dose ifosfamide as part of combination chemotherapy with autologous bone marrow transplantation [25].
• Mobilization of peripheral blood progenitor cells by sequential administration of interleukin-3 and granulocyte-macrophage colony-stimulating factor following polychemotherapy with etoposide, ifosfamide, and cisplatin [26].
• In these patients, an even higher number of circulating tumor cells was detected after chemotherapy with VP16, ifosfamide, and cisplatin (VIP) followed by granulocyte colony-stimulating factor (G-CSF) [27].
• (3) In comparison with CD3+ CTL, CD3- NK cells are more resistant to an ifosfamide treatment because they have higher initial GSH levels and a more than fourfold higher relative rate of GSH synthesis [28].

Associations of ifosfamide with other chemical compounds

• Combination bleomycin, ifosfamide, and cisplatin chemotherapy in cervical cancer [12].
• In 3 sequential clinical trials, conducted from January 1993 to August 2000, we treated 150 patients with relapsed or primary refractory DLBCL with ifosfamide, carboplatin, and etoposide (ICE) chemotherapy followed by HDT/ASCT for patients with chemosensitive disease [29].
• Differential effects of ifosfamide on the capacity of cytotoxic T lymphocytes and natural killer cells to lyse their target cells correlate with intracellular glutathione levels [28].
• 4-Hydroxyifosfamide (4-OH-IF), the activated form of ifosfamide, depletes GSH levels in T cells and natural killer (NK) cells; this is accompanied by a decrease in T-cell and NK-cell function [30].
• Granulocyte colony-stimulating factor support was mandatory after the high-dose ifosfamide/cisplatin/doxorubicin combination [31].

Gene context of ifosfamide

• Overall, the present study establishes that liver microsomal CYP2B and CYP3A preferentially catalyze cyclophosphamide and ifosphamide 4-hydroxylation, respectively, suggesting that liver P-450-inducing agents targeted at these enzymes might be used in cancer patients to enhance drug activation and therapeutic efficacy [32].
• Differential activation of cyclophosphamide and ifosphamide by cytochromes P-450 2B and 3A in human liver microsomes [32].
• In one human hepatocyte culture that contained the polymorphically expressed CYP3A5 in addition to the more widely expressed CYP3A4, only CYP3A4 was induced by cyclophosphamide, ifosfamide, and rifampin [33].
• Expressed CYP2A6, -2B6, -2C8, -2C9, and -3A4 were catalytically competent in hydroxylating cyclophosphamide and ifosphamide [32].
• The present study investigates the activity of four individual human CYP2C enzymes and their allelic variants in cyclophosphamide and ifosfamide activation as an initial attempt to gain insight into the underlying basis for the large interpatient differences in the clinical pharmacokinetics and metabolism of these anticancer drugs [34].

Analytical, diagnostic and therapeutic context of ifosfamide

• The records of all patients who received a chemotherapy regimen containing etoposide, ifosfamide, or cisplatin after failing to respond to primary chemotherapy were also reviewed [35].
• A comprehensive review of preclinical data and clinical trials with ifosfamide is presented [1].
• Increased risk of ifosfamide-induced renal Fanconi's syndrome after unilateral nephrectomy [36].
• Induction consisted of ifosfamide, etoposide, doxorubicin, dactinomycin, cyclophosphomide, and vincristine, and a split course of hyperfractionated radiotherapy [37].
• Sequential dose-intensive paclitaxel, ifosfamide, carboplatin, and etoposide salvage therapy for germ cell tumor patients [38].

References