Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0036690 (sepsis)
 59,461 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Advanced non-small cell lung cancer (NSCLC) denotes those of TNM stage III and IV. NSCLC has its specific characteristics in respect of oncological behaviour, molecular biology, sensitivity to chemotherapy (CT) and radiotherapy (RT), and requires different therapeutic strategies in comparison with small cell lung cancer. The therapies include: (1) surgery in combination with new effective drugs is resulted in improved RR from 15% a decade ago to 40-60% today. Cisplatin (C-DDP) is the most attractive drug in the treatment of NSCLC, in lengthening the life-span of Stage IV NSCLC patients and as an indispensable sensitizer in RT. Taxinol, Gemcitabine (GEM), Navelbine (NVB), Edatrexate (ETX), CPT-11 and high dose Epirubicin (EPI HD) are recommended as new effective drugs. Response rates recently reported for the combination CT with the drugs mentioned above for NSCLC are from 30-65%, and with 8-42 weeks of MST. Induction or neoadjuvant therapies for advanced NSCLC, with 40-69% of RR, 25-29% of complete resection rate, 8-34% of CR and 17-45% of one year SR are reviewed. Eight random studies comparing MST between CT with C-DDP and best supportive care for NSCLC are statistically significant. (2) RT for Stage III NSCLC with 2 year and 5 year survivals of 20 and 5% respectively. Although such outcome is hardly acceptable, RT sensitizer, modified RT techniques and chemoradiotherapy (CRT) are imperative to improve the effect of RT in advanced NSCLC. Clinical literature suggest that CRT is better than RT, though without marked difference. Further studies and sufficient follow-up are necessary to judge the efficacy in terms of long-term survival and toxic reaction. (3) Biological therapy: gene therapy of NSCLC is still in the experimental and developmental stage. Of biological response modifier (BRM), alpha IFN in 11 cases of NSCLC with RR of 9% and MST of 14 months, IL-2 and LAK cell treatment in 11 cases with RR of 9% and MST of 18 months are reported. Instillation of BRM such as IL-2 or alpha-IFN into the pleura after drainage of cancerous effusion has been reported as the most effective for those whose RR is of 80-90% and the clinical response time is fairly long. Hematological cytokine as a protective adjuvant therapy against CT/RT toxicity makes high dose of CT possible and raises the response and patient tolerance. In multimodality therapy, it plays an important role to reduce post CT infection and septicemia.
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PMID:Non-surgical therapy for patients with advanced non-small cell lung cancer. 976 13

Forty-three patients with ovarian cancer were entered on this trial and treated with intravenous (iv) cyclophosphamide (C) and doxorubicin (A), and intraperitoneal (ip) cisplatin (DDP), every 21 days for eight cycles. Following iv hydration, the cisplatin was administered through an intraperitoneal catheter in 2 L of 0.9% normal saline with a 4-h dwell. All patients are evaluable for overall and progression-free survival with a median follow-up of 70 months (range: 3-162 months); 39 patients are evaluable for response. All complete responses were surgically confirmed. The median age was 59 (range 28-82 years); 3 patients were stage IC, 5 were IIC, 14 patients were stage III (optimally debulked), 14 patients were stage III (suboptimally debulked), and 7 patients were stage IV. Two patients had received prior alkylator therapy. Six of 8 patients with Stage IC or II remain without evidence of disease at a mean of 12 years following chemotherapy. Of 14 optimally debulked stage III patients, there were 7 complete responses, 3 partial responses, 1 patient with stable disease, and 3 inevaluable patients. Of 14 suboptimally debulked stage III patients there were 4 complete responses, 4 partial responses, 3 with stable disease, 2 progressions on treatment, and 1 inevaluable patient. Five-year progression-free and overall survivals for stage III optimally debulked patients are 21 and 64%, respectively. At 10 years, progression-free and overall survivals for this group are 21 and 29%, respectively. Toxicity included neutropenia (complicated by sepsis in 2 patients), infrequent thrombocytopenia, and mild anemia. Three patients developed transient serum creatinine elevations >2.0 mg/dl; however, decreased creatinine clearance was noted in 93/258 (36%) of evaluable courses which required a cisplatin dose reduction per protocol. Controllable hypomagnesemia, nausea, and emesis were also observed. We conclude that the combination of iv CA and ip DDP is an effective regimen with long-term progression-free and overall survivals that compare favorably with those of other published studies of intravenous or intraperitoneal chemotherapy. This report is unusual in terms of the prolonged follow-up for all patients enrolled. These long-term results lend further support to recently published trials documenting the efficacy of intraperitoneal chemotherapy for patients with this disease.
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PMID:Phase II trial of intraperitoneal cisplatin with intravenous doxorubicin and cyclophosphamide in previously untreated patients with advanced ovarian cancer-long-term follow-up. 1060 Mar

Cisplatin (CDDP), epirubicin (EPI) and docetaxel have single agent activity against urothelial transitional cell carcinoma (TCC). We evaluated the efficacy and toxicity of this combination in locally advanced or metastatic urothelial TCC. Patients with urothelial TCC who had no prior chemotherapy (prior adjuvant chemotherapy > 6 months allowed) were eligible for entry the study. Eligibility criteria were performance status 0-3, granulocyte count (AGC) > or = 1.5 (10(9)/l), platelet count > or = 100 (10(9)/l), clearance creatine > or = 60 ml/min and total bilirubin level < or = 1.5 mg/dl. Treatment consisted of EPI 40 mg/m2 intravenous push, docetaxel 75 mg/m2 in 1 h infusion with premedication and CDDP 75 mg/m2 with pre- and posthydration. Treatment was repeated every 21 days. Antiemetics with dexamethasone and 5-HT3 antagonists were used routinely. Prophylactic haematopoietic growth factors were not used. Patients were evaluated for toxicity weekly and assessed for response every two cycles of treatment. 32 patients were entered into the study and 30 patients (7 with locally advanced and 23 with metastatic disease) were assessable for response. There were 9 (30.0%) complete responses (2, 28.6% in locally advanced and 7, 30.4% in metastatic disease) and 11 (36.7%) partial responses (3, 42.9% in locally advanced and 8, 34.8% in metastatic disease) with an overall response rate (RR) of 66.7% (71.5% in locally advanced, 65.2% in metastatic disease). Overall median survival was 14.5 months (15 months for locally advanced, 12.5 months for metastatic disease). The median duration of response in patients with metastatic disease was 8.5 months. 16 (53.3%) patients required one dose reduction and 5 (16.7%) patients required two dose reductions for a nadir AGC < or = 500/mm3. Four episodes of febrile neutropenia and sepsis occurred. No patient had a dose reduction or treatment delay for any other grade 3/4 toxicity. There were no treatment delays due to myelotoxicity. Alopecia was universal. Non-haematological toxicity including mucositis, fluid retention, allergy, cutaneous toxicity, diarrhoea and neurotoxicity were mild and infrequent. The combination of EPI, docetaxel and CDDP is an active regimen for urothelial TCC. The response rate and toxicity were comparable with the M-VAC (methotrexate, vinblastine, doxorubicin, cisplastin) regimen. Phase III trials comparing this regimen with M-VAC are warranted.
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PMID:Chemotherapy with cisplatin, epirubicin and docetaxel in transitional cell urothelial cancer. Phase II trial. 1074 Dec 98

On the basis of the demonstrated single-agent activity of cisplatin in patients with advanced cervical cancer and the observation of in vitro synergism between this agent and decitabine, a new DNA hypomethylating agent, we designed a phase II trial in which the combined use of the two agents are used as first-line therapy in patients with recurrent and/or metastatic disease. Eligible patients were those with histopathologically proven diagnosis of squamous cell carcinoma of the cervix, which was not considered suitable for curative surgery and/or irradiation, having measurable disease, leukocyte counts more than or equal to 4,000/microl, thrombocyte counts more than or equal to 100,000/microl, serum creatinine more than or equal to 1.5 mg/dl, and normal liver function tests. Initial dose of cisplatin was 40 mg/m(2), whereas decitabine was 50 mg/m(2) for 3 consecutive days every 21 days. Because of toxicity, the dose of cisplatin was reduced to 30 mg/m(2). Twenty-five patients were included in the study; 24 of them were eligible for the evaluation of toxicity, whereas 21 of them were eligible for the evaluation of tumor responses. Nineteen (79.2%) patients had received prior radiotherapy. A total of 75 cycles of chemotherapy were administered to the patients, with a median of 3 cycles (range: 1-8) per patient. The most frequently observed side effect was neutropenia, which was National Cancer Institute- Common Toxicity Criteria grades III and IV in 68.0% of cases. One patient died of complications caused by drug-related neutropenic sepsis. The most common nonhematologic grades III and IV toxicities were nausea and vomiting, which occurred in 17.3% and 9.3% of the cycles, respectively. Of a total of 21 patients evaluable for tumor response, 8 (38.1%) achieved a partial response, whereas stable disease was documented in 5 cases (23.8%). Median progression-free interval (PFI) was 16 weeks, and median survival was 19 weeks (95% CI 7.9-31.2). Objective responses were more frequent in patients with metastatic lesions in nonirradiated sites. Cisplatin- decitabine combination was moderately active in patients with advanced squamous cell carcinoma of the cervix, mainly in patients presenting with metastatic disease at previously nonirradiated sites. However, this regimen produced significant hematologic toxicity. Further studies with this combination including a larger patient population, preferably with the concomitant administration of hematopoietic growth factors, are warranted.
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PMID:Phase II trial of cisplatin plus decitabine, a new DNA hypomethylating agent, in patients with advanced squamous cell carcinoma of the cervix. 1239 92

Cisplatin induction therapy followed by combination chemotherapy employing cisplatin, doxorubicin, and ifosfamide was administered to 25 consecutive patients with FIGO stage III:or IV epithelial ovarian cancer as first-line therapy following cytoreductive surgery. A median of seven (3-10) courses of combination chemotherapy were administered. Myelotoxicity necessitated dose attenuation in 20 (80%) patients. Microscopic hematuria was observed in one (4%) patient. Serious central neurotoxicity occurred in two (8%) patients. A surgically documentable response to therapy was observed in 16 of 19 (84%) patients who underwent second-look laparotomy. Thirteen (68%) patients had a surgical complete response, three (12%) patients had a surgical partial response, and three (12%) patients demonstrated progression of disease. The estimated two-year survival for the study population was 81%. The results observed in the current study were compared to those reported for a population of 40 patients with advanced ovarian cancer treated with cisplatin, doxorubicin, and cyclophosphamide (PAC). Patients treated with PAI had significantly (p=0.04) fewer episodes of sepsis, a significantly (p=0.02) greater percentage of patients requiring dose reduction secondary to myelotoxicity, and a significantly (p=0.02) higher surgical complete response rate. The two-year survival for patients treated with PAI of 81% and that for patients treated with PAC of 68%, do not differ significantly (p=0.39). The two-year disease-free survival for patients treated with PAI of 34% and the two-year disease-free survival of 55% for patients treated with PAC do not differ significantly (p=0.99). The combination of cisplatin, doxorubicin, and ifosfamide is effective as first-line therapy in the treatment of advanced epithelial ovarian cancer, but a significant advantage over the less costly standard regimen which employs cisplatin, doxorubicin and cyclophosphamide is not demonstrable in the current study.
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PMID:Comparison of Ifosfamide versus cyclophosphamide in combination with Cisplatin and Doxorubicin (adriamycin), as first-line therapy for advanced epithelial ovarian-cancer - report of a pilot-study. 2160 16

Cisplatin (CP) is one of the most effective chemotherapeutics in the treatment of human cancers. However, the beneficial effects of CP are limited by the toxic effects, especially nephrotoxicity. Fluorofenidone (AKFPD) is a promising multifunctional antifibrosis pyridinone drug discovered by our group. But there is no evidence of its protective effects against acute kidney injury (AKI). Therefore, we investigated the protective effects of AKFPD on CP-induced AKI in vivo and in vitro. Compared with the model group, treatment with AKFPD effectively ameliorated kidney damages. In order to elucidate the mechanisms, we discovered that AKFPD treatment notably alleviated generation of reactive oxygen species, reduced the phosphorylation levels of MAPKs (ERK1 and 2, JNKs, and p38), suppressed inflammatory response, inhibited apoptosis, and abated the expression of CP transporters (organic cation transporter 2 and copper transport protein 1) compared with the model group. Moreover, because renal ischemia reperfusion injury (IRI)-induced AKI and LPS-induced AKI are the major models representative of renal transplantation-correlated AKI and sepsis-related AKI, which are also the main causes of AKI, we have also proved the effectiveness of AKFPD on these models. In conclusion, these findings suggest that AKFPD is a potent drug for CP-, IRI-, and LPS-caused AKI and elucidate the underlying mechanism.-Jiang, Y., Quan, J., Chen, Y., Liao, X., Dai, Q., Lu, R., Yu, Y., Hu, G., Li, Q., Meng, J., Xie, Y., Peng, Z., Tao, L. Fluorofenidone protects against acute kidney injury.
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PMID:Fluorofenidone protects against acute kidney injury. 3166 38

Ogilvie syndrome or intestinal pseudo-obstruction is a clinical syndrome characterized by autonomic imbalance affecting peristalsis of colon leading to obstructive signs and symptoms. The etiologies commonly implicated are drugs affecting the cholinergic system, narcotics, electrolyte imbalance, severe sepsis, cancer, major surgery, and renal and cardiac failure. Ogilvie syndrome secondary to chemotherapy is a very rare phenomenon with very few reports in the literature. Cisplatin-induced neuropathy has been reported to occur when the cumulative dose exceeds 360 mg/m<sup>2</sup>. It manifests predominantly as peripheral sensory neuropathy with autonomic neuropathy occurring very rarely in a subset of patients. All the reported cases to date who presented with autonomic dysfunction secondary to cisplatin also had peripheral sensory neuropathy. Herein, we report a case of metastatic nonseminomatous germ cell tumor treated with cisplatin based regimen, who presented with severe intestinal pseudo-obstruction when the cumulative dose exceeded 400 mg/m<sup>2</sup> without any other manifestation of neuropathy. To our knowledge this is the first such case reported in the literature.
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PMID:Ogilvie Syndrome in a Refractory Germ Cell Tumor Treated with Vinblastine, Ifosfamide and Cisplatin Regimen. 3317 81


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