Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0042963 (vomiting)
 31,883 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Ifosfamide was administered to 21 patients with recurrent or disseminated lung cancer at a dose of 4.0 gm/M2 iv every 3 weeks. The response rate was 33% with an additional 14% showing no response or stable disease. At a dose of 1.2 gm/M2 daily for 5 days every 4 weeks, 57% of 14 patients responded with 35% showing no response or stable disease. The majority of the patients (28) had epidermoid carcinoma. Two (7%) had complete response with 9 (32%) showing partial responses. Other responses included 1/2 oat cell carcinomas and 3/6 large cell undifferentiated carcinomas. Toxicity was equal in both regimens for nausea, vomiting, increased serum LDH and neutropenia but the 5 day program had significantly less hemorrhagic cystitis. Survival was greatly influenced by response. There was no statistical difference in overall length of response between responders and the non responding/stable disease patients. But these two groups had a very significant survival advantage when compared to those patients with increasing disease. Similarly, there was a significant improvement in response duration for the low dosage regimen. Therefore, the low dose 5 day regimen is recommended because of its response rate, it has less hemorrhagic cystitis and it has better patient acceptance in that it can be given as an outpatient and does not require a Foley catheter.
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PMID:Ifosfamide in the treatment of recurrent or disseminated lung cancer: a phase II study of two dose schedules. 20 39

Biological response modifiers (BRMs) have greatly modified the immunotherapy of tumors. Interleukin-2 (IL-2) has brought about metastasis regression in some cases of malignant tumors, however, when given systemically, it results in high toxicity. More recently, the subcutaneous administration of IL-2 (combined with alpha-interferon, alpha-IFN) seems to be capable of offering the same chances of therapeutic response, but this time with a lower level of toxicity. The Authors report an evaluation of toxicity in 22 patients treated with a combination of IL-2 + alpha-IFN i.m. with or without chemotherapy. The side-effects present in the majority of cases were: fever, diarrhea and asthenia. Approximately 50% of the patients had nausea/vomiting, mucositis, skin rashes, and slight leukopenia. The following side-effects were noted to a much lesser degree, thrombocytopenia, alterations in hepatic and dizziness and cystitis. Only one patient reached 4th degree toxicity, with mucositis, asthenia and skin rash. All the other patients received the treatment without suspensions for toxicity. Biological evaluations will enable us to determine in the future, the cases which can benefit from therapeutic intensification and thus it would seem opportune at this time to use therapy with acceptable toxicity.
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PMID:Evaluation of toxicity in 22 patients treated with subcutaneous interleukin-2, alpha-interferon with and without chemotherapy. 128 42

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

N-Acetylcysteine is useful as a mucolytic agent for treatment of chronic bronchitis and other pulmonary diseases complicated by the production of viscous mucus. It is also used as an antidote to paracetamol (acetaminophen) poisoning and found to be effective for the prevention of cardiotoxicity by doxorubicin and haemorrhagic cystitis from oxazaphosphorines. After an oral dose of N-acetylcysteine 200 to 400 mg the peak plasma concentration of 0.35 to 4 mg/L is achieved within 1 to 2 hours. Although the data are conflicting, it appears that the administration of charcoal may interfere with drug absorption, with up to 96% of the drug adsorbed on to the charcoal. Information on absorption in the presence of food or other drugs is not available. The volume of distribution ranges from 0.33 to 0.47 L/kg and protein binding is significant, reaching approximately 50% 4 hours after the dose. Pharmacokinetic information is not available as to whether or not N-acetylcysteine crosses the blood-brain barrier or placenta, or into breast milk. Renal clearance has been reported as 0.190 to 0.211 L/h/kg and approximately 70% of the total body clearance is nonrenal. Following oral administration, reduced N-acetylcysteine has a terminal half-life of 6.25h. Little is known of the metabolism of this agent, although it is believed to be rapidly metabolised and incorporated on to proteins. The major excretory product is inorganic sulphate. Frequently reported side effects are nausea, vomiting and diarrhoea. Biochemical and haematological adverse effects are observed but are not clinically relevant. Drug interactions of clinical significance have been observed with paracetamol, glutathione and anticancer agents.
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PMID:Clinical pharmacokinetics of N-acetylcysteine. 202 5

An ongoing trial of combination chemotherapy using ifosfamide (Holoxan), epirubicin and 5-fluorouracil was started in 1987. A total of 30 patients with metastatic cancer of the breast received 1.5 g/m2 i.v. ifosfamide over 60 min on days 1-3, 50 mg/m2 i.v. epirubicin on day 1 and 500 mg/m2 i.v. 5-fluorouracil on day 1, followed by mesna (Uromitexan) given at 20% of the ifosfamide dose at 0, 4 and 8 h. The courses were repeated every 4 weeks. In all, 198 courses were given, ranging from 3 to 13 (median, 7) cycles/patient. The mean age of the 30 patients was 48 years (range, 35-66 years); 5 had not previously received chemotherapy and the others had failed prior cytotoxic and endocrine therapy. Overall, 28 patients were evaluable, 7 (25%) showed a complete response and 15 (54%) had a partial response, for an overall response rate of 22/28 (79%). Three patients showed stable disease with improved symptoms, and in three cases disease progression occurred. The median duration of response was 9 months (range, 3-20 months). Median survival was 11 months for all patients, 15 months for CRs, 10 months for PRs, 6 months for stable disease and 12 months for progressive disease (PD). Survival for the 22 responding patients was 12 months. Toxicity was acceptable and included alopecia, mucositis, nausea, vomiting, diarrhoea, mild cystitis and myelosuppression. Epirubicin did not appear to produce cardiac toxicity, and ifosfamide with mesna did not seem to result in severe urotoxicity. Chemotherapy with ifosfamide, epirubicin and 5-fluorouracil proved to be effective for treatment of advanced breast cancer and should be further studied in large, controlled trials.
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PMID:Treatment of metastatic breast cancer with the combination of ifosfamide, epirubicin and 5-fluorouracil. 234 52

Fourteen patients with refractory metastatic breast cancer were treated with high dose chemotherapy and autologous hematopoietic stem cell rescue. All patients received cyclophosphamide (7.5 g/m2 over 3 days) and thiotepa (150-225 mg/m2 over 3 days), three patients in addition received melphalan (4.5 mg/kg), and seven patients received carmustine (150-562 mg/m2). Toxicities included pancytopenia, infection, hemorrhagic cystitis, skin rash, nausea, vomiting, diarrhea, and mucositis. There was one toxic death secondary to sepsis and ventricular tachycardia. The overall response rate was 77% including a 15% complete response rate. The overall median survival for all patients was 6.0 months (range 2-22 months). The median survival for nonresponders was 3.5 months. The median duration of response was 89 days (range 40-262). In our experience high dose chemotherapy with autologous stem cell reinfusion produces a high response rate in refractory breast cancer. However, because of the short duration of response and overall survival, we feel this type of therapy should be utilized earlier in the course of disease.
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PMID:High dose chemotherapy with autologous hematopoietic stem cell support in the treatment of refractory stage IV breast carcinoma. 250 79

Fifteen patients with Stage IV lung cancer both untreated and previously treated were enrolled into a high-dose chemotherapy program with multiple alkylating agents and autologous bone marrow reinfusion. Eight patients received cyclophosphamide at 7.5 gm/m2 over 3 days with thiotepa escalated from levels of 1.8 mg/kg to 6.0 mg/kg over 3 days. Seven patients received the above dose of cyclophosphamide plus thiotepa at 675 mg/m2 and oral melphalan escalated from levels of 0.75 mg/kg to 2.5 mg/kg over 3 days. Both regimens are part of larger Phase I-II clinical studies. The median time to recovery of more than 500 granulocytes and more than 50,000 platelets per microliter was 16 and 27 days, respectively. Two patients died as a consequence of severe, overwhelming infections during their period of aplasia. Of the 13 evaluable patients, no patients achieved a complete response and seven patients (47%) obtained a partial response. The median duration of response was 12 weeks. Other nonhematologic toxicities included nausea/vomiting, diarrhea, mucositis, skin rash, hemorrhagic cystitis, and cardiomyopathy. Since there are substantial toxicities associated with high-dose chemotherapy and responses of such brief duration, further investigation with these drug combinations is not warranted.
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PMID:High-dose, multiple-alkylator chemotherapy with autologous bone marrow reinfusion in patients with advanced non-small cell lung cancer. 253 52

We describe a patient with systemic lupus erythematosus (SLE) and overlapping syndrome who had repeated gastrointestinal (GI) symptoms such as nausea, vomiting and malabsorption. With a subacute process, she developed paralytic ileus and contracted bladder, and died of perforation of the ileum. When 13 reported cases with lupus cystitis were reviewed, an extremely strong correlation between GI and urinary tract symptoms was observed, indicating the presence of a unique subgroup of SLE.
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PMID:Lupus cystitis and performation of the small bowel in a patient with systemic lupus erythematosus and overlapping syndrome. 268 79

A case of lupus cystitis in a 23-year-old male is reported. The patient began to complain of diarrhea and vomiting in October, 1985. When the diagnosis of systemic lupus erythematosus (SLE) was established at the Department of Internal Medicine in our hospital, he was referred to our clinic for examination of pollakisuria on November 22. DIP revealed a loss of bladder distensibility, and bilateral hydronephrosis and hydroureter. Transurethral cold cup biopsies revealed subcutaneous edema. A diagnosis of lupus cystitis was made and he was treated with steroids, which resulted in symptomatic and radiographic improvement.
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PMID:[A case of lupus cystitis]. 273 71

Eleven patients with advanced nonseminomatous germ cell tumors (NSGCT), who relapsed after or were refractory to standard dose cisplatin-based remission induction chemotherapy, were treated in a phase II clinical trial with VP 16-213 2500 mg/m2 and cyclophosphamide 7 g/m2. Both drugs were given in maximally tolerable doses regarding extramedullary toxicity. Urothelial damage due to cyclophosphamide was prevented by the administration of mesnum. Autologous bone marrow was infused on day 7 to prevent long lasting medullary toxicity. Because of the disappointing results in the first three patients, a second treatment step was added. The next eight patients were treated with 2500 mg/m2 VP 16-213 divided and given on days 1-2-3 and after full bone marrow recovery with total doses of VP 16-213 2000 mg/m2 plus cyclophosphamide 7 g/m2 divided and given on days 29-30-31, followed by autologous bone marrow transplantation (ABMT) on day 35. Toxicity to high-dose VP 16-213 plus cyclophosphamide followed by ABMT consisted of mucositis, nausea, vomiting and diarrhea. No cardiac toxicity or hemorrhagic cystitis occurred. The mean duration of leukopenia and thrombopenia was 14 and 13 days respectively. The additional, preceding treatment with VP 16-213 as a single agent caused mucositis, and leukopenia and thrombopenia for a mean number of 9 and 6 days respectively. Seven responses were obtained: two complete responses of 46 and 66+ weeks respectively and five partial responses with a median response duration of 12 weeks. The median survival time was 40 weeks. This regimen of one or two courses with maximally tolerable doses of VP 16-213 plus cyclophosphamide and ABMT is not sufficient to salvage a substantial number of patients with relapsing or refractory NSGCT.
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PMID:Chemotherapy with maximally tolerable doses of VP 16-213 and cyclophosphamide followed by autologous bone marrow transplantation for the treatment of relapsed or refractory germ cell tumors. 283 93


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