Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0006142 (breast cancer)
 160,383 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.
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PMID:Ifosfamide/mesna. A review of its antineoplastic activity, pharmacokinetic properties and therapeutic efficacy in cancer. 172 Mar 82

Ifosfamide has single agent activity in advanced breast cancer and may potentiate the activity of doxorubicin. The combination of ifosfamide 5 g/m2 and doxorubicin 40 mg/m2 every 3 weeks for 4 cycles was used to treat 77 patients with advanced breast cancer. Fifty three patients had not received prior chemotherapy. All patients had one or more poor prognostic features, including tumor expression of epidermal growth factor receptor in 11/12 tested. The overall response rate was 74% (95% confidence intervals 62%-83%). The median survival was 9.4 months. The principal toxicities were febrile neutropenia and ifosfamide encephalopathy each in 6% of patients. A high percentage of the projected dose intensity was administered. This is a highly active combination with acceptable toxicity in advanced breast cancer, although the long term survival remains poor. Further exploration of ifosfamide in combination chemotherapy for advanced breast cancer is warranted.
Breast Cancer Res Treat 1994
PMID:Results of chemotherapy using ifosfamide with doxorubicin in advanced breast cancer. 804 61

Subacute encephalopathy developed in four patients within one to two months after undergoing high-dose chemotherapy and bone marrow transplantation or peripheral blood progenitor (stem) cell transplantation for breast cancer, acute myeloid leukemia, and non-Hodgkin's lymphoma. None of the patients had previously known neurologic disorders, central nervous tumor or infection. Two patients presented with generalized tonic, clonic seizures, and two with confusion and lethargy. In all patients lumbar puncture and CT scans of the brain were normal, while magnetic resonance imaging (MRI) demonstrated multifocal predominantly white matter lesions. Phenytoin therapy was given to the two patients with seizures and all four patients improved without specific therapeutic intervention. Repeat MRIs became normal within three months. We report a delayed and transient encephalopathy which appears to be a unique complication of high-dose cytotoxic chemotherapy. The corresponding brain lesions may not be appreciated on CT scans, suggesting an expanded role for MRI studies in patients who develop neurologic findings while undergoing high-dose cytotoxic therapy.
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PMID:Delayed, transient encephalopathy after marrow transplantation: case reports and MRI findings in four patients. 884 58

This synthesis of the literature on the quality of life in relation to radiotherapy is based on 78 scientific articles, including 12 randomized studies, 25 prospective studies, and 20 retrospective studies. These studies involve 9884 patients. Radiotherapy is often organ-preserving, which inherently promotes a better quality of life. Many quality of life aspects related to radiotherapy have been studied, but seldom by prospective randomized studies that compare radiotherapy to other treatment (eg, surgery or chemotherapy). Radiotherapy involves numerous physical and psychological symptoms, mainly during the course of treatment. Examples include skin irritation and fatigue. Radiotherapy directed at the brain has delayed effects, in children treatment carries a substantial risk for lowering the IQ. The risk for encephalopathy in adults is probably underestimated. Patients with cancer in the head and neck may experience adverse side effects in the irradiated area long after the conclusion of radiotherapy. There are no confirmed differences in quality of life between breast cancer patients receiving adjuvant radiotherapy and those receiving chemotherapy. Impotency problems and urinary incontinence appear following radical surgery and radiotherapy for prostate cancer. The risk for delayed complications is low after radiotherapy for testicular cancer. Patients receiving radiotherapy for gynecologic cancers are often troubled by local side effects long after the conclusion of treatment.
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PMID:Radiotherapy for cancer. Quality of life. 915 7

We analysed a series of 24 adult patients with idiopathic (10 cases) and paraneoplastic (14 cases) opsoclonus-myoclonus syndrome (OMS) to ascertain possible differences in clinical course and response to immunotherapies between both groups. Associated tumours were small-cell lung cancer (SCLC) (nine patients), non-SCLC (one patient), breast carcinoma (two patients), gastric adenocarcinoma (one patient) and kidney carcinoma (one patient). Patients with paraneoplastic OMS were older [median age: 66 years versus 40 years (P = 0.006) of those with idiopathic OMS] and had a higher frequency of encephalopathy (64% versus 10%; P = 0.02). Serum from 10/10 idiopathic and 12/14 paraneoplastic OMS patients showed no specific immunoreactivity on rat or human brainstem or cerebellum, lacked specific antineuronal antibodies (Hu, Yo, Ri, Tr, glutamic acid decarboxylase, amphiphysin or CV2) and did not contain antibodies to voltage-gated calcium channels. The two paraneoplastic exceptions were a patient with SCLC, whose serum contained both anti-Hu and anti-amphiphysin antibodies and a patient with breast cancer who had serum anti-Ri antibodies. The clinical course of idiopathic OMS was monophasic except in two elderly women who had relapses of the opsoclonus and mild residual ataxia. Most idiopathic OMS patients made a good recovery, but residual gait ataxia tended to persist in older patients. Immunotherapy (mainly intravenous immunoglobulins or corticosteroids) seemed to accelerate recovery. Paraneoplastic OMS had a more severe clinical course, despite treatment with intravenous immunoglobulins or corticosteroids, and was the cause of death in five patients whose tumours were not treated. By contrast the eight patients whose tumours were treated showed a complete or partial neurological recovery. We conclude that idiopathic OMS occurs in younger patients, the clinical evolution is more benign and the effect of immunotherapy appears more effective than in paraneoplastic OMS. In patients aged 50 years and older with OMS who develop encephalopathy, early diagnosis and treatment of a probable underlying tumour, usually SCLC, is indicated to increase the chances of neurological recovery. At present, there are no immunological markers to identify the adult patients with paraneoplastic OMS.
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PMID:Clinical outcome in adult onset idiopathic or paraneoplastic opsoclonus-myoclonus. 1115 70

Coagulation disorders are common in cancer patients. In patients with solid tumors, a low-grade activated coagulation can result in systemic and cerebral arterial or venous thrombosis. Cancer treatments may also contribute to this coagulopathy, which usually, but not exclusively, occurs in the setting of advanced malignant disease. There may be TIAs or cerebral infarctions. Because of the widespread distribution of cerebral thromboses, there may be a superimposed encephalopathy; sometimes this is the only sign. Concurrent systemic thrombosis is present in many patients and is a useful clue to the diagnosis. In cerebral venous occlusion, the initial symptom is usually a headache. Except for cerebral intravascular coagulation that is unassociated with NBTE, neuriomaging studies usually demonstrate one or more parenchymal infarctions. MRI or MRV may demonstrate venous thrombosis. The laboratory evidence of coagulopathy is difficult to distinguish from the asymptomatic coagulopathy that often accompanies advanced cancer, and the test results must be interpreted cautiously. NBTE can be diagnosed by transesophageal echocardiography. There is no established treatment for the thrombotic coagulopathy associated with cancer, but anticoagulation should be considered. In leukemia and lymphoma, the coagulopathy is typically acute DIC that can lead to systemic and brain hemorrhages. It is especially common in acute myelogenous leukemias. The clinical signs of cerebral hemorrhage are fulminant and may be fatal. The bleeding usually occurs in the brain or subdural compartment, and rarely in the subarachnoid space. The diagnosis can be suspected by the clinical setting and by systemic thrombosis or hemorrhage. It can be established by examination of the peripheral smear, the platelet count, and tests of coagulation function. Therapy of acute DIC is controversial and should be individualized for the clinical setting. Cerebrovascular disorders can complicate metastatic or primary tumor in the brain, skull, dura, or leptomeninges. The clinical signs of infarction are indistinguishable from other causes of stroke, except that tumor-related venous occlusion will usually first produce signs of increased intracranial pressure. The diagnosis of tumor-related infarction can usually be established by neuroimaging studies that show infarction and may show extracerebral sites of tumor. CSF examination is useful in diagnosing leptomeningeal metastasis. A search for lung or cardiac tumor should be performed when embolic tumor infarction is suspected. Primary or metastatic tumors in the brain or dura may hemorrhage, producing the initial clinical signs of the brain tumor or a change in chronic signs induced by the tumor. There are helpful clues to a neoplastic hemorrhage on brain CT or MRI scans. The brain hemorrhage may require evacuation and the underlying tumor will usually require additional antineoplastic treatment. Hyperleukocytosis (extreme elevation of the cell count) in acute myelogenous leukemia is a less common cause of brain hemorrhage in recent years because of improved methods to lower the cell count. Cerebral arterial or venous thrombosis is sometimes the result of cancer therapy. The attribution of thrombosis to chemotherapy in many published cases is only speculative, because carefully conducted prospective studies that include investigation for other thrombotic causes are not available. The best-known associations with thrombosis are L-asparaginase, which is typically used in the induction therapy of acute lymphocytic leukemia, and combination hormonal therapy and chemotherapy for breast cancer. Radiation to the head and neck, typically administered for head and neck epithelial cancers or lymphoma, may result in delayed carotid atherosclerosis. The distribution of stenosis or occlusion is within the radiation portal and is typically more extensive than is atherosclerosis that develops in the absence of radiation. Small clinical series suggest that surgical treatment is equally effective as in nonirradiated carotid atherosclerosis. In children, the cerebral vessels can be affected by brain radiation resulting in stenosis or occlusion. Brain hemorrhages can result from chemotherapy effects on the hemostatic system or a microangiopathic anemia. Hemorrhages from radiation-induced vascular abnormalities are rare. Opportunistic infections, especially fungal infections, can complicate cancer or its treatment. Septic cerebral emboli may result in focal cerebral signs, seizures, or encephalopathy. Sometimes there is an associated hemorrhagic vasculitis or cerebritis. Rarely, mycotic aneurysms may bleed. A high index of suspicion is needed to diagnose fungal infection because of the difficulty in culturing the organism from the blood or CSF. A clinician can usually establish the cause of stroke in the cancer patient by performing a careful review of the clinical setting--including the type and extent of cancer and the type of antineoplastic therapy--in which the stroke occurred. Systemic thrombosis, embolism, or hemorrhage can be a clue to the cause, and appropriate neuroimaging and coagulation studies to aid in the diagnosis are available. Therapy may ameliorate symptoms or prevent further episodes. The identification of one of these unusual stroke syndromes that leads to the diagnosis of an occult and treatable cancer can be particularly rewarding.
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PMID:Cerebrovascular complications in cancer patients. 1269 Jun 49

Neurotoxic side effects of chemotherapy occur frequently and are often a reason to limit the dose of chemotherapy. Since bone marrow toxicity, as the major limiting factor in most chemotherapeutic regimens, can be overcome with growth factors or bone marrow transplantation, the use of higher doses of chemotherapy is possible, which increases the risk of neurotoxicity. Chemotherapy may cause both peripheral neurotoxicity, consisting mainly of a peripheral neuropathy, and central neurotoxicity, ranging from minor cognitive deficits to encephalopathy with dementia or even coma. In this article we describe the neurological adverse effects of the most commonly used chemotherapeutic agents. The vinca-alkaloids, cisplatin and the taxanes are amongst the most important drugs inducing peripheral neurotoxicity. These drugs are widely used for various malignancies such as ovarian and breast cancer, and haematological cancers. Chemotherapy-induced neuropathy is clearly related to cumulative dose or dose-intensities. Patients who already have neuropathic symptoms due to diabetes mellitus, hereditary neuropathies or earlier treatment with neurotoxic chemotherapy are thought to be more vulnerable for the development of chemotherapy-induced peripheral neuropathy. Methotrexate, cytarabine (cytosine arabinoside) and ifosfamide are primarily known for their central neurotoxic side effects. Central neurotoxicity ranges from acute toxicity such as aseptic meningitis, to delayed toxicities comprising cognitive deficits, hemiparesis, aphasia and progressive dementia. Risk factors are high doses, frequent administration and radiotherapy preceding methotrexate chemotherapy, which appears to be more neurotoxic than methotrexate as single modality. Data on management and neuroprotective agents are discussed. Management mainly consists of cumulative dose-reduction or lower dose-intensities, especially in patients who are at higher risk to develop neurotoxic side effects. None of the neuroprotective agents described in this article can be recommended for standard use in daily practise at this moment, and further studies are needed to confirm some of the beneficial effects described.
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PMID:Neurotoxic complications of chemotherapy in patients with cancer: clinical signs and optimal management. 1288 62

Synthetic coumarin (benzopyrone) was launched in France in 1988 for the adjuvant therapy of lymphoedema of the upper limb following radiosurgical treatment of breast cancer. Further to the reporting of hepatic reactions, a national survey has been carried out. The survey dealt with 22 cases reported to the pharmacovigilance regional centres and 20 to Knoll France company (five duplicate cases) up to June 1996. Thirty-four cases corresponding to an elevation of ALT over 2N and/or alkaline phosphatase over 1.5N (criteria chosen for selection in this survey) had been taken into account. Among these cases, a causal relationship was considered likely or probable for 15 of them. Two positive rechallenges were reported. The hepatic reactions observed between 2 to 6 months of treatment in two-thirds of the cases (average dose: 90 mg/day; i.e. recommended dose) was essentially cytolytic in 85% of the cases, with jaundice in 14 cases and hyperbilirubinaemia reported in five other cases. In 23 cases (68%), the increase of ALT exceeded 10N. Of the patients 41% were hospitalized. Severe liver failure with encephalopathy justified liver transplantation once and likely led to encephalopathy and fatal evolution in two other cases. The evolution was favourable in the other cases. The drug was prescribed for other uses than the registered indication in more than 50% of these cases. No risk factors could be identified in the survey. This survey provides a strong signal for potential hepatotoxicity of coumarin (likely due to the production of a reactive metabolite in some patients exhibiting a coumarin 7-hydroxylation deficiency).
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PMID:French pharmacovigilance survey evaluating the hepatic toxicity of coumarin. 1507 59

Cognitive dysfunction has been reported in subsets of cancer patients and has been related to their underlying disease (small-cell lung cancer [SCLC]) or to a specific therapy (prophylactic cranial irradiation in SCLC, chemotherapy in breast cancer). Patients with uremic encephalopathy who have had their hemoglobin levels normalized by erythropoietic therapy have shown improved cognitive function in some studies. The mechanism responsible for the improvement is unknown and might reflect either a direct neuroprotective effect of erythropoietins on the central nervous system or the benefit of increased tissue oxygenation secondary to the correction of peripheral anemia. Whether erythropoietic agents can affect the cognitive dysfunction reported among some cancer patients is currently being investigated. The current state of knowledge about the use of erythropoietic agents for neuroprotection or the treatment of neurologic syndromes is described.
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PMID:Erythropoietic agents in the management of cancer patients. Part 2: studies on their role in neuroprotection and neurotherapy. 1533 Mar 71

Amphiphysin-IgG was identified in 71 patients among 120,000 evaluated serologically for paraneoplastic autoantibodies. Clinical information was available for 63 patients. Cancer was detected in 50 (mostly limited), proven histologically in 46, and was imaged intrathoracically in 4 patients (lung, small-cell [27] and non-small cell [1]), breast [16] and melanoma [2]). Neurological accompaniments included (decreasing frequency): neuropathy, encephalopathy, myelopathy, stiff-man phenomena, and cerebellar syndrome. In a case examined neuropathologically, parenchymal T-lymphocyte infiltration (predominantly CD8(+)) was prominent in lower brainstem, spinal cord, and dorsal root ganglion. Coexisting paraneoplastic autoantibodies, identified in 74% of patients, predicted a common neoplasm and indicated other neuronal autoantigen targets that plausibly explained several neurological manifestations; for example, P/Q-type Ca(2+)-channel antibody with Lambert-Eaton syndrome (n = 5), anti-neuronal nuclear antibody type 1 with sensory neuronopathy (n = 7), K(+)-channel antibody with limbic encephalitis (n = 1) or neuromyotonia (n = 1), and collapsin response-mediator protein-5-IgG with optic neuritis (n = 3). Patients with isolated amphiphysin-IgG (n = 19) were more likely to be women (with breast cancer, p < 0.05) and to have myelopathy or stiff-man phenomena (p < 0.01). Overall, a minority of women (39%) and men (12%) had stiff-man phenomena. Only 10% of women (some with lung carcinoma) and 4% of men fulfilled diagnostic criteria for stiff-man syndrome.
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PMID:Amphiphysin autoimmunity: paraneoplastic accompaniments. 1598 30


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