Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0019829 (Hodgkin's disease)
 30,247 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Ifosfamide is an oxazaphosphorine alkylating agent with a broad spectrum of antineoplastic activity. It is a prodrug metabolised in the liver by cytochrome P450 mixed-function oxidase enzymes to isofosforamide mustard, the active alkylating compound. Mesna, a uroprotective thiol agent, is routinely administered concomitantly with ifosfamide, and has almost eliminated ifosfamide-induced haemorrhagic cystitis and has reduced nephron toxicity. Therapeutic studies, mostly noncomparative in nature, have demonstrated the efficacy of ifosfamide/mesna alone, or more commonly as a component of combination regimens, in a variety of cancers. In patients with relapsed or refractory disseminated nonseminomatous testicular cancer, a salvage regimen of ifosfamide/mesna, cisplatin and either etoposide or vinblastine produced complete response in approximately one-quarter of patients. As a component of both induction and salvage chemotherapeutic regimens, ifosfamide/mesna has produced favourable response rates in small cell lung cancer, paediatric solid tumours, non-Hodgkin's and Hodgkin's lymphoma, and ovarian cancer. Induction therapy with ifosfamide/mesna-containing chemotherapeutic regimens has been encouraging in non-small cell lung cancer, adult soft-tissue sarcomas, and as neoadjuvant therapy in advanced cervical cancer. As salvage therapy, ifosfamide/mesna-containing combinations have a palliative role in advanced breast cancer and advanced cervical cancer. Ifosfamide/mesna can elicit responses in patients refractory to numerous other antineoplastic drugs, including cyclophosphamide. With administration of concomitant mesna to protect against ifosfamide-induced urotoxicity, the principal dose-limiting toxicity of ifosfamide is myelosuppression; leucopenia is generally more severe than thrombocytopenia. Reversible CNS adverse effects ranging from mild somnolence and confusion to severe encephalopathy and coma can occur in approximately 10 to 20% of patients after intravenous infusion, and the incidence of neurotoxicity may be increased to 50% after oral administration because of differences in the preferential route of metabolism between the 2 routes of administration. Other adverse effects of ifosfamide include nephrotoxicity, alopecia, and nausea/vomiting. In general, intravenously administered mesna is associated with a low incidence of adverse effects; however, gastrointestinal disturbances are common following oral administration. Thus, ifosfamide/mesna is an important and worthwhile addition to the currently available range of chemotherapeutic agents. It has a broad spectrum of antineoplastic activity and causes less marked myelosuppression than many other cytotoxic agents. At present, the role of ifosfamide/mesna in refractory germ cell testicular cancer is clearly defined; however, its overall place in the treatment of other forms of cancer awaits delineation in future well-controlled comparative studies.
 ...
PMID:Ifosfamide/mesna. A review of its antineoplastic activity, pharmacokinetic properties and therapeutic efficacy in cancer. 172 Mar 82

A 37 year old man without coronary risk factors or known heart disease showed progression of Hodgkin's disease after radiation and multiple chemotherapy. One day after the first cycle of chemotherapy with methotrexate, Ifosfamide and etoposide, he had an acute myocardial ischemia. The creatinin-kinase was elevated up to 325 U/l. Coronary angiography showed a thrombus in the left anterior descending coronary artery (LAD), while the other coronary arteries were normal. Ventriculography showed an apical akinesia. After 7 days of treatment with heparin coronary angiogram was normalized, without any stenosis in the LAD. To our knowledge this is the first documented case of a coronary artery thrombosis and myocardial ischemia after chemotherapy in a patient without coronary heart disease. We conclude that chemotherapy can cause myocardial ischemia by coronary artery thrombosis in patients without prior heart disease.
 ...
PMID:[Acute coronary thrombosis and myocardial ischemia following chemotherapy of Hodgkin's disease]. 220 11

We report on a 28 year old Turkish woman, who was admitted to our hospital with the symptoms of malabsorption and protein-loosing enteropathy. Histologically, on duodenal biopsy, a lymphoplasmacellular infiltration of the submucosa with partial to subtotal atrophy of the villi was found. An immunoproliferative small intestinal disease (IPSID) was diagnosed. A short remission whilst on a glutenfree diet and tetracycline therapy, was followed by a laparatomy because of ileus in the small intestine. A high-grade-malignant Non-Hodgkin's Lymphome of B-cell type with intracellular production of alpha-Heavy-Chains (AHCD) was diagnosed histologically. Following chemotherapy with CEOP-IMVP-Dexa (Cyclophosphamide, Epidoxorubicin, Vincristine, Prednisolone, Ifosfamide, VP-16, Dexamethason, Methotrexat) the patient is still in complete remission three years after starting the therapy. We discuss here a case of AHCD in IPSID, the differential diagnosis of protein losing enteropathy and malabsorption, and we also present conservative (diet, medical treatment) and operative therapies.
 ...
PMID:Malabsorption associated with a high-grade-malignant non-Hodgkin's lymphoma, alpha-heavy-chain disease and immunoproliferative small intestinal disease. 779 20

Modern combination chemotherapy cures about one third of patients with non-Hodgkin's lymphomas (NHL) [3]. Attempts to increase this proportion by more intensive chemotherapeutic regimens have failed so far in randomized trials [4, 5]. Dose intensity has been reported to be important for cure [8]--a factor which can be enhanced by hematopoietic growth factors--but addition of recombinant human granulocyte colony-stimulating factor (rhG-CSF) to intensive chemotherapy did not improve response on survival in a controlled study published recently [10]. Therefore, we tried to design a regimen which might be more appropriate for combination with growth factors, using pulse chemotherapy rather than continuous treatment and employing drugs of low stem-cell toxicity. Ifosfamide (Ifo) appeared to be ideal because it is effective even in some resistant cases [1] and might act synergistically with anthracyclines by reducing intracellular glutathione levels [9]. Epirubicin (Epi) was favored because of its low hemato- and cardiotoxicity [2]. These drugs, together with etoposide (VP-16) had been found to be very effective in relapsed cases [7]. Methotrexate (Mtx) was added because it penetrates the spinal fluid. Moreover, we chose granulocyte/macrophage colony-stimulating factor (rhGM-CSF) as an adjunct cytokine because this not only enhances neutrophil regeneration [6] but might also have antitumor effects, as suggested by an uncontrolled study in sarcomas [11]. This report summarizes our experiences regarding feasibility, toxicity, and responses with this new regimen obtained in a pilot study.
 ...
PMID:IEVM chemotherapy with rhGM-CSF support for aggressive non-Hodgkin's lymphomas: a pilot study. 847 59

Neuroblastomas, nephroblastomas, malignant mesenchymal tumors, including rhabdomyosarcomas, Ewing's sarcomas, osteosarcomas, brain tumors, and non-Hodgkin's lymphomas respond to ifosfamide monotherapy. Ifosfamide has found an established place in the treatment of these pediatric malignancies. Ifosfamide has been shown to be an especially valuable agent in brain tumors in patients with a poor-prognosis medulloblastoma. The combination of ifosfamide with other cytotoxic drugs is more effective than ifosfamide medication alone. Ifosfamide has to be given with mesna to prevent bladder toxicity, but other toxic side effects, such as neurotoxicity, nephrotoxicity, and gonadal damage, are more difficult to prevent. Ifosfamide has proven to be an important asset in the treatment of cancer in children.
 ...
PMID:Ifosfamide in the treatment of pediatric malignancies. 871 2

In three new approved indications (non Hodgkin's lymphoma, Hodgkin's lymphoma and acute lymphoblastic leukaemia) and in three previously existing indications (ovarian cancer, soft tissue sarcomas and osteogenic sarcomas), non comparative trials show that ifosfamide can induce tumour regression in patients who relapse after a first course of chemotherapy (sometimes containing cyclophosphamide). But clinical assessment has not yet formally demonstrated that this leads to a significant increase in survival time and/or quality of life, mainly because of toxicity. In cervical cancer, a new indication, a comparative trial shows higher tumour response rates with the ifosfamide + cisplatin combination than with cisplatin alone. However, the greater toxicity of the combination and the lack of any increase in survival must both be taken into account. In breast cancer and lung cancer comparative trials show no difference in efficacy between cyclophosphamide and ifosfamide, while toxicity may be worse with ifosfamide. Ifosfamide has no specific value in these approved indications. The same applied to ENT cancer, against which ifosfamide seems to have little activity.
 ...
PMID:Ifosfamide: new idications-new dose strength. Limited evidence of effectiveness. 1018 82

Methotrexate (MTX) is the chemotherapeutic for which the serum levels can be detected. If the MTX level is detected in time, high toxicity risk can be decreased. In this study, intermediate doses of MTX (1 g/m2) infusions are administered to B-cell non-Hodgkin lymphoma patients between 3 and 13 years old. The toxicity of MTX in accordance with serum levels and the toxicity of other combined drugs are investigated. Blood samples were collected consecutively, and MTX levels were detected by high-performance liquid chromatography. When hematological, gastrointestinal, and renal toxicity scores were compared with the 24-h serum levels of MTX, they showed a significant positive correlation. Hematological toxicity scores increased by Ifosfamide, Etoposide, and Cytarabine combined with MTX without altering the serum levels. Antibiotic combination with MTX has no effect on the toxicity scores. In conclusion, if MTX is combined with other myelosuppressive, hepatotoxic, and nephrotoxic drugs, the measurement of MTX serum levels alone is not a sufficient parameter to show the toxicity.
 ...
PMID:Intermediate dose of methotrexate toxicity in non-Hodgkin lymphoma. 1018 22

Ifosfamide is an alkylating agent with proven efficacy in the treatment of solid tumours and malignant lymphomas. Because it causes only mild to moderate myelosuppression, ifosfamide is often used in combination regimens with other agents. Ifosfamide has been mainly used in therapy of lymphoma as a component of salvage regimens, but high-dose ifosfamide is also effective in the mobilization of peripheral stem cells for treatment of patients with relapsed or refractory lymphoma with regimens containing autologous stem cell transplantation. Based on promising data with a new combination regimen containing idarubicin, etoposide and ifosfamide (IIVP-16) in patients with poor-risk non-Hodgkin's lymphoma, we have performed a phase II study using DIZE (dexamethasone 20 mg i.v. days 1-4, idarubicin 8 mg/m2 i.v. days 1 + 2, ifosfamide 1.0 g/m2 continuous infusion (c.i.) days 1-4, and etoposide 160 mg/m2 c.i. days 1-4) in patients with relapsed or refractory Hodgkin's and non-Hodgkin's lymphoma. In 43 evaluable patients, the response rate was 58%, including 11 complete remissions (CR) and 14 partial remissions (PR). The mean duration of response was 8 months (1-30). Myelosuppression was generally mild with mean duration of neutropenia < 1000/microL of 2.5 days (range 0-18) and thrombocytopenia < 25,000/microL of 1.5 days (0-17). Thus, DIZE is an effective and safe regimen for pretreated patients with aggressive lymphoma. These results appear to compare favourably with other salvage regimens such as IMVP-16 or DHAP. In conclusion, salvage regimens containing ifosfamide can play an important role in patients who are not eligible for high-dose chemotherapies. Moreover, ifosfamide might also have a role in reducing tumour burden and selecting those patients who qualify for HDCT.
 ...
PMID:The role of ifosfamide in the treatment of relapsed and refractory lymphoma. 1148

Ifosfamide is an alkylating agent with a broad spectrum of activity in solid tumors and hematological malignancies. In this review we will illustrate its use in the treatment of lymphomas and Hodgkin's disease and the results of the principal studies which have investigated ifosfamide-containing regimens. Ifosfamide has been mainly used, in combination with other drugs, as a component of salvage regimens for relapsed or primarily refractory lymphoma. These regimens induced a variable clinical response rate (complete remissions ranging from 6 up to 73% and overall response rate from 24 to 72%). High-dose ifosfamide, in combination with etoposide or mitoxantrone, showed a good potential for mobilization of peripheral stem cells while reducing the tumor burden. Ifosfamide-based regimens are also being evaluated in the treatment of newly diagnosed patients in sequential, response-based protocols, using many non-cross-resistant drugs.
 ...
PMID:Ifosfamide in hematological malignancies of adults. 1458 56

Ifosfamide (IFO), an alkylating agent used for the management of solid organ tumors, can cause reversible Fanconi's syndrome and acute kidney injury. Karyomegalic interstitial nephropathy (KIN) is a rare form of chronic tubulointerstitial nephritis, initially described as a familial nephropathy in adults. So far, four cases of KIN have been reported in pediatric and adolescent population following treatment with IFO. We report a 22-year-old man who developed renal dysfunction following IFO therapy for relapsed Hodgkin's lymphoma. Renal biopsy revealed chronic tubulointerstitial nephritis with atypical tubular epithelial cells showing nuclear enlargement and hyperchromasia, consistent with a diagnosis of KIN. The renal function improved following a short course of corticosteroids.
...
PMID:Karyomegalic interstitial nephropathy following ifosfamide therapy. 2751 5


1 2 Next >>