Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027497 (nausea)
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Pirarubicin, a new antineoplastic antibiotic of anthracycline derivative, was injected into the pleural cavity in 15 patients with malignant pleural effusion. The dose of pirarubicin was 40 mg or 80 mg/body. All 15 patients were evaluable for both efficacy and toxicity. Since one evaluable patient received two courses of intrapleural administration of pirarubicin, we evaluated a total of 16 courses. Overall response rate was 81.3% with 7 CR cases, 6 PR cases and 3 NR cases. As toxicities, transient elevation of fever was observed in 81.3%, chest pain in 37.5%, appetite loss in 18.8%, nausea in 12.5% and bone marrow suppression in 6.3% of 16 courses, but no alopecia was observed. Between 40 mg group (n = 8) and 80 mg group (n = 8), no significant difference was observed in response rate, response duration, survival duration or toxicities except for fever. Fever over 38 degrees C was observed in all (100%) the 80 mg group, which was significantly higher than 50% in the 40 mg group. Response duration in cases with fever over 38 degrees C (n = 12) was significantly longer than in cases with maximum fever under 38 degrees C (n = 4). Intrapleural administration of pirarubicin was considered to be effective for the treatment of malignant pleural effusion without severe toxicities.
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PMID:[Intrapleural administration of pirarubicin in the treatment of malignant pleural effusion]. 165 58

Most of the symptoms from a malignant tumor are caused by local invasion by the tumor, or obstruction, either at the site of the primary disease or by metastases. However, tumors can produce symptoms at a remote site. Patients with gastrointestinal malignancy may present with symptoms which include dysphagia, nausea, vomiting, abdominal pain, diarrhea, bleeding and ascites. Palliation gastrectomy delays or prevents these symptoms. About 30% of gastric carcinomas are inoperable at the time of presentation. Chemotherapy is rarely effective in the palliation of gastric carcinoma. Laser irradiation can be delivered to assay site accessible to fibreoptic endoscopy, which is an advantage over endocavity irradiation or diathermy fulguration. Ascites is a common and disabling implication in patients with advanced malignant disease. Spironolactone will increase urinary sodium excretion significantly and control their ascites. If spironolactone fails to control, useful control can be achieved by draining the ascites. Patients with carcinoma of the lung may present with symptoms that include cough, bloody sputum and dyspnoea. Pain in the chest wall is usually secondary to invasion of the parietal pleura, ribs or intercostal nerves. Lesions in the medial portion of the right upper lobe, or mediastinal metastases, may invade or compress the superior vena cava, causing venous hypertension with oedema of the head and arms. The patients may complain of dyspnoea, dysphagia, stridor and headaches. Radiotherapy can be expected to improve the quality of life for these patients. Successful palliation of symptoms is almost related to tumor regression. The problems of obstruction and bleeding from malignant tumor is common. Recently, laser techniques have been applied to aid in palliation of these problems. Malignant effusion may occur early and be the first signs of metastases. The aim of therapy is to evacuate the fluid and induce pleural adhesion. One of the sad situations that we have to face is the patient with recurrent cancer which complains of various symptoms. The relief of symptoms is the most important palliative therapy to them.
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PMID:[Palliative therapy in cancer. 3. Palliation of the symptoms from a malignant tumor (1)]. 169 82

Twenty-eight patients with malignant pleural effusion received instillation of cisplatin (CDDP) into the pleural cavity to examine the pharmacokinetics and side effects of CDDP Thirteen patients received high-dose CDDP (120 mg/m2-160 mg/m2) in combination with sodium thiosulfate (STS), while 15 others received CDDP alone (80 mg/m2). Total Pt and non-protein-bound Pt (free Pt) concentrations in the pleural effusion and plasma were determined by flameless atomic absorption spectrometry. In one patient, Pt concentrations of intact CDDP and STS-bound CDDP were determined using high performance liquid chromatography and flameless atomic absorption spectrometry. Instillation of CDDP at 160 mg/m2 into the pleural cavity was achieved by concurrent use of STS in the large dose (STS 20 g/m2 1 hr later, totalling 625-fold molar ratio to CDDP). When CDDP was combined with STS, there was alleviation in hematological, renal and auditory toxicity but not in nausea, vomiting or anorexia. When CDDP was instillated into the pleural cavity at 150 mg/m2 (in combination with STS equivalent to 200-fold molar ratio to CDDP), a high Pt concentration of intact CDDP could be maintained in the pleural effusion over a prolonged period of time, recording 8.80 micrograms/ml even as late as 12 hr after instillation. On the other hand nearly all of the free Pt concentration for the first 2 hr was considered to be due to intact CDDP. Once systemically administered, STS quickly moved into the pleural effusion, binding with CDDP in the pleural cavity and thus probably reducing its anti-tumor effect. STS did not greatly affect the plasma concentration of total Pt when it was administered at a 100-fold molar ratio to CDDP, yielding only p poor effect. Our findings suggest that malignant pleural effusion could be effectively treated by the instillation of CDDP 80 mg/m2 into the pleural cavity.
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PMID:[Studies on an appropriate intra thoracic administration of cisplatin and sodium thiosulfate in malignant pleural effusion]. 319 43

Pirarubicin (4'-O-tetrahydropyranyladriamycin), a new anthracyline derivative, was administered as a single agent into the pleural cavity of 42 patients (total 46 courses) with malignant pleural effusion at a dose of 20, 40, 60 or 80 mg/body. All 46 courses were evaluable for non-hematological toxicities. Fever and chest pain (> or = WHO grade 2) were seen in 67.4% and 13.0% of courses, respectively. Patients receiving a dose of 80 mg/body developed fever of > or = 39 degrees C in 45.5%, and chest pain lasting more than three days and requiring pentazocine more than three times in 36.4%. In contrast, patients receiving a dose of < or = 60 mg/body presented these toxicities in only 8.6% and 2.9%, respectively. Nausea-vomiting (> or = WHO grade 2) was observed in only 4.3% of the total 46 courses and alopecia was not observed. Thirty-eight courses (36 patients) were evaluable for hematological toxicities. Myelosuppression (leukocyte nadir count < or = 1900, WHO grade 3 or 4) was seen in four courses (10.5%), and thrombocytopenia (< or = 49,000, WHO grade 3 or 4) in only two (5.3%). Although the mean AUC (0-24) for pirarubicin in plasma during the four courses that produced myelosuppression was significantly higher than that during the 11 courses without myelosuppression, the difference in the mean dose was not significant. Furthermore, no significant correlation was shown between dose (mg/m2) and AUC in plasma. It is considered that myelosuppression is not a dose-related toxicity at a dose of 20-80 mg/body. The dose-limiting toxicity was fever or chest pain, although unexpected myelosuppression was also encountered. The maximum tolerated dose was 80 mg/body. With regard to clinical efficacy, the overall response rate was 73.7% in 38 evaluable courses (38 patients). The mean T(1/2) of pirarubicin concentration in pleural effusion and plasma was 22.1 h and 8.8 h, respectively. We recommend a dose of 40 or 60 mg/body pirarubicin for this pleurodesic treatment.
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PMID:Intrapleural pirarubicin (4'-O-tetrahydropyranyladriamycin) for treatment of malignant pleural effusion. 889 73

The aim of this study was to evaluate the effectiveness and side-effects of intrapericardial administration of cisplatin (IAC), in cases of abundant malignant pericardial effusion (MPE) and/or cardiac tamponade occurring in the course of adenocarcinoma of the lung (AL). Fifteen consecutive patients with abundant MPE and AL (4 females and 11 males; mean age 54 yrs) entered this prospective study. Following pericardiocentesis and insertion of a polyurethane catheter, the pericardial fluid was drained. Malignant aetiology of the pericardial fluid was confirmed by cytological examination. After confirmation of MPE, cisplatin (10 mg in 20 mL normal saline) was instilled directly into the pericardial space, over a period of 5 min for 3-5 consecutive days. Treatment was considered successful (response) if the patient survived 30 days without recurrence of symptoms of abundant MPE, and no other interventions directed to the pericardium were required. Response was achieved in 10 patients (67%). The mean (+/-SEM) dose of cisplatin was 56 (+/-18.9) mg. There were no complications related to the pericardiocentesis. Transient atrial fibrillation was detected in one patient. Mild nausea also occurred in one case. No hypotension or retrosternal pain was observed. Sclerotization of the pericardium and pericarditis constrictiva were detected after IAC in only one case. Cisplatin administered directly into pericardial space is effective and safe. Intraperitoneal administration of cisplatin appears to be the method of choice in the treatment of recurrent malignant pleural effusion in patients with primary adenocarcinoma of the lung. Sclerosis of the pericardial space is a very rare complication observed after intraperitoneal administration of cisplatin therapy.
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PMID:Intrapericardial administration of cisplatin in treatment of metastatic pericardial involvement in adenocarcinoma of the lung. 927 Feb 45

We examined the efficacy, toxicity, and survival rate of patients treated with local administration of adriamycin (ADM) for malignant pleural effusion and pericardial effusion in breast cancer. From May 1996 to December 2002, we injected ADM into the pleural cavity for 21 courses and into the pericardial cavity for 2 courses in 18 patients. Thirteen patients showed CR (including 2 cases were injected into pericardial cavity), 2 PR, and 4 PD, and the overall response rate was 78.9%. Toxicities included nausea/vomiting, elevated fever, chest pain, and so on in 15 patients (83.3%). No severe toxicities, however, were observed. The overall survival rate after the removal of the drainage tube was 42.5% at 1 year and 16.5% at 2 years. The survival in patients with a first recurrence, and CR or PR was significantly better than other patients. We conclude that local administration of ADM is useful for treatment, without severe toxicities, of malignant pleural effusion and pericardial effusion in breast cancer.
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PMID:[Local administration of adriamycin (ADM) for malignant pleural effusion and pericardiac effusion in breast cancer]. 1471 66

There is an urgent need for new therapies to treat non-small cell lung cancer (NSCLC) because current chemotherapy regimens are of limited effectiveness. The role of vascular endothelial growth factor in promoting tumor angiogenesis, in maintaining existing vasculature, and in resistance to traditional therapies, together with its negative prognostic significance in NSCLC, make it an appropriate target for therapy. Bevacizumab (Avastin), a monoclonal antibody directed against vascular endothelial growth factor, has shown promise in treating a number of different cancers. In a recent Phase II trial in patients with advanced metastatic NSCLC, the addition of bevacizumab to standard carboplatin/paclitaxel chemotherapy significantly increased the time to progression and increased the response rate when compared with chemotherapy alone. This was particularly impressive in the subset of patients with non-squamous histology. Bevacizumab is generally well tolerated and did not appear to increase the incidence or severity of nausea/vomiting, neuropathy and renal toxicity, which are typically associated with carboplatin/paclitaxel chemotherapy. Adverse events in Phase I and II studies included hypertension, thrombosis, proteinuria (with occasional nephrotic syndrome), and epistaxis. Serious tumor-related bleeding episodes (hemoptysis/hematemesis) seem to be the main safety concern in patients with NSCLC, with squamous cell histology as a possible risk factor. Present ongoing studies are under way in NSCLC including (a) a Phase II neo-adjuvant study in combination with paclitaxel and carboplatin in patients with stage IB-IIA NSCLC; (b) a Phase I/II study of bevacizumab in combination with the epidermal growth factor receptor tyrosine kinase inhibitor agent, Tarceva, in patients with previously treated NSCLC; and (c) an Eastern Cooperative Group randomized Phase III study of paclitaxel and carboplatin with/without bevacizumab in patients with previously untreated IIIB (malignant pleural effusion) or metastatic NSCLC. These studies will help to establish the role of bevacizumab in NSCLC.
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PMID:Anti-vascular endothelial growth factor monoclonals in non-small cell lung cancer. 1521 70

We investigated the effectiveness and complications of intrathoracic infusion with a combination of cisplatin, OK-432, and minocycline for malignant pleural effusion. All patients were hospitalized with chest tube drainage of pleural effusion until the daily drainage volume was less than 100 ml. Twenty-five mg of minocycline, 1 to 3 KE of OK-432, and 5 to 10 mg of cisplatin were instilled into the pleural space. The administration was repeated until drainage effusion disappeared. Therapeutic effect was evaluated according to the following criteria: (1) excellent, no fluid reaccumulation for at least 4 weeks as determined by chest radiogram and clinical evaluation; (2) effective, fluid reaccumulation less than 50% of original effusion with no need of thoracentesis for symptomatic relief within 4 weeks after treatment; and (3) failure, reaccumulation of more than 50% of the original effusion requiring thoracentesis to relieve symptoms within 4 weeks of treatment. Twelve patients with malignant effusion received the combination treatment; 11 patients had primary lung cancer and one had metastatic lung tumor from cancer of the rectum. In all cases, the histology or cytology revealed adenocarcinoma. Eleven of the 12 patients had an excellent response with relief of clinical symptoms. The remaining case failed to show any improvement. Complications such as local pain, fever, nausea, and vomiting were mild and transient. We conclude that combination administration of low-dose minocycline, OK-432, and cisplatin into the thoracic cavity for malignant effusion is an effective alternative treatment with the potential for improvement of the general condition and reduced morbidity.
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PMID:[Intrathoracic infusion with a combination of low-dose minocycline, OK-432 and cisplatin for malignant pleural effusion]. 1579 17

Malignant pleural effusion is typical of complications in advanced lung cancer patients, most of whom complain of dyspnea. The standard treatment for symptomatic pleural effusion is intrapleural administration of a chemical agent. In Japan, OK-432, a streptococcal preparation, and cisplatin (CDDP) have been among the most frequently used chemical agents. There have been very few reports on the efficacy of chemical agents for malignant pleural effusion. We compared therapeutic efficacy and toxicity of intrapleural OK-432 with CDDP in a case-control study. The subjects consisted of 32 lung cancer patients with malignant pleural effusion who were admitted to our hospital between January 2000 and June 2004. The therapeutic efficacy was assessed from duration of chest drainage after intrapleural administration, response rate, time to progression of malignant pleural effusion, and survival time. No statistically significant difference was observed for therapeutic efficacy. Although the OK-432-treated group had only grade 1 fever, chest pain, nausea, the CDDP-treated group had a grade 2 increase in creatinine and grade 3 nausea. Intrapleural OK-432 seemed to be better tolerated in the treatment of malignant pleural effusion than intrapleural CDDP.
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PMID:[Comparison of intrapleural OK-432 and cisplatin for malignant pleural effusion in lung cancer patients]. 1612 16

To assess the effect and toxicity of hypotonic cisplatin treatment (HPT) consisting of the intrapleural administration of cisplatin in distilled water for malignant pleural effusion in patients with non-small-cell lung cancer (NSCLC). Non-small-cell lung cancer patients with cytologically proven and previously untreated malignant pleural effusion were enrolled into this study. Firstly, the lung was fully re-expanded by a tube thoracostomy, and then 25 mg cisplatin in 500 ml of distilled water was instilled through a chest tube and then the tube was clamped. After 1 h, the tube was declamped and allowed to drain. The chest tube was removed when the pleural effusion volume decreased to 200 ml or less per day. A complete response (CR) was considered to occur when the pleural effusion disappeared. A partial response (PR) was determined to occur when the volume of pleural effusion remained under (1/4) of hemithorax. The response at 4 weeks was evaluated by an extramural review. Out of 84 patients enrolled from February 1998 to August 2002, 80 patients were eligible and analysed in the present study. The toxicity of HPT was acceptable. Neither a haematological toxicity of any grade nor grade 4 nonhaematological toxicity was observed. Grade 3 nonhaematological toxicities were observed, including nausea (4%), vomiting (3%), pyothorax (1%) and dyspnoea (1%). The median time of drainage from HTP was 4 days. Twenty-seven (34%) and 39 (49%) patients achieved CR and PR, respectively, for an overall response rate of 83% (95% confidence interval, 74-91%). The median duration of the response was 206 days. The median survival time of all patients was 239 days. Hypotonic cisplatin treatment for malignant pleural effusion of NSCLC is therefore considered to be feasible and effective. A phase III study of HPT is thus warranted.
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PMID:Intrapleural hypotonic cisplatin treatment for malignant pleural effusion in 80 patients with non-small-cell lung cancer: a multi-institutional phase II trial. 1694 Sep 82


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