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)

A phase I study was performed to establish the optimum dose for combination therapy with infusional cisplatin and irinotecan (CPT-11) in non-small-cell lung cancer (NSCLC). The subjects were 20 patients with a performance score of 0-2 with untreated advanced NSCLC. Cisplatin was administered by 5-day continuous intravenous infusion at 20-25 mg/m2 per day. CPT-11 was administered by bolus infusion at a starting dose of 20 mg/m2 on days 1 and 8 or 60 mg/m2 per day on day 1 alone, followed by serial increments of 20 mg/m2. Since grade 4 granulocytopenia was observed in two of the five patients receiving 20 mg/m2 per day cisplatin (days 1-5) and 100 mg/m2 CPT-11 (day 1), and since one of them developed severe pneumonia and sepsis associated with the granulocytopenia, the regimen was considered to be intolerable. In the same patient, grade 4 thrombocytopenia and grade 3 diarrhea were observed. Therefore, the optimum dose appeared to be 20 mg/m2 per day (days 1-5) for cisplatin and 80 mg/m2 (day 1) for CPT-11. The side effects were grade 2 diarrhea in one of three patients, and grade 2 vomiting in three patients, but grade > or = 2 hemotoxicity was not observed. This combined regimen resulted in a partial response in 9 out of 19 assessable patients. The dose-limiting factor in this combination therapy was granulocytopenia, and a high efficacy rate was obtained.
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PMID:A phase I study of irinotecan and infusional cisplatin for advanced non-small-cell lung cancer. 902 73

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

Metabolic conversion of CPT-11 is a major route of elimination of this new topoisomerase 1 inhibitor. Presently, recommendations for dose adjustments of CPT-11 in patients with liver dysfunction are lacking. We describe the case of a patient with metastatic colon cancer with liver dysfunction treated with CPT-11 at two different dose levels (100 mg/m2 and 30 mg/m2, single dose, administered as a 90-min i.v. infusion). The lactones and carboxylates of CPT-11 and SN-38 were determined by high-performance liquid chromatography. SN-38 glucuronide was determined after deglucuronidation. The procedures allowed intrapatient comparison of pharmacokinetics and metabolism of the drug. Severe side effects were encountered, which could be explained by the reduced clearance of CPT-11 and its metabolites. These included neutropenic fever with culture-proven septicemia, thrombocytopenia, somnolence, diarrhea, and signs and symptoms of transient hepatic failure. Our findings offer important data for the further development of guidelines for dose reduction of CPT-11 in patients with liver dysfunction.
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PMID:Altered pharmacokinetics and metabolism of CPT-11 in liver dysfunction: a need for guidelines. 1077 61

A phase II study of fractionated administration of irinotecan (CPT-11) and cisplatin (CDDP) in patients with non-small-cell lung cancer (NSCLC) was conducted. Between January 1996 and January 1998, 44 previously untreated patients with stage IIIB or IV NSCLC were enrolled. CDDP at a dose of 60 mg x m(-2) was given first and followed by CPT-11 at a dose of 50 mg x m(-2). Both drugs were given by 1-hour infusion on days 1 and 8, and repeated every 4 weeks up to 4 cycles. 42 patients were evaluated for response and 44 for survival and toxicity. 20 patients (48%: 95% confidence interval 32-63%) achieved an objective response. The median duration of responses was 8 months, and the median survival time and the 1-year survival rate were 12.5 months and 56.8%, respectively. Major toxicities were neutropenia and diarrhoea. Grade 3 or 4 neutropenia occurred in 70.5% of the patients and one patient died of sepsis. Grade 3 or 4 diarrhoea was experienced in 25.0%, but manageable by conventional therapy. In conclusion, fractionated administration of CPT-11 and CDDP was highly effective for advanced NSCLC with manageable toxicities.
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PMID:Fractionated administration of irinotecan and cisplatin for treatment of non-small-cell lung cancer: a phase II study of Okayama Lung Cancer Study Group. 1143 95

The combination of CPT-11 with 5-fluorouracil (5-FU) in advanced colorectal cancer (ACC) represents an attractive approach. A phase II study was conducted to assess the tolerance and efficacy of CPT-11 in combination with leucovorin-modulated bolus plus infusional 5-FU given according to the de Gramont regimen in chemonaive patients with ACC. Fifty-four patients with histologically confirmed ACC were enrolled. The patients' median age was 65 years; 30 (55.5%) patients were men; performance status (World Health Organization) was 0 in 27 (50%) patients, 1 in 22 (41%), and 2 in 5 (9%). Patients received leucovorin (200 mg/m2/d) as a 2-hour intravenous infusion, followed by 5-FU as an intravenous bolus at 400 mg/m2/d, and then as a 22-hour continuous infusion at 600 mg/m2/d, repeated on 2 consecutive days. CPT-11 (180 mg/m2; 30-minute intravenous infusion) was administered on day 1, simultaneously with leucovorin administration. This cycle was repeated every 2 weeks. Complete response was achieved in 4 patients (8%) and partial response in 19 (37%) (overall response rate: 45%; 95% CI: 24-50.5%). Stable disease was achieved in 16 (31%) patients and progressive disease in 13 (25%). The median duration of response and the median TTP were 5 and 8 months, respectively. After a median follow-up period of 11 months, 33 (61%) patients are still alive; the median overall survival has not yet been reached. Thrombocytopenia and anemia were very rare. Grade III/IV neutropenia developed in 19 patients (36%); febrile neutropenia developed in 4 patients, and 1 of them died of sepsis. Grade IV diarrhea was seen in 7 (13%) patients, and 4 of them required hospitalization. Grade III and IV mucositis was observed in two (4%) and one (2%) patients, respectively. Other toxicities were mild. The combination of CPT-11 and bolus plus infusional 5-FU is a relatively well-tolerated and effective first-line treatment in ACC. Final results from large phase III trials are awaited to clarify whether the CPT-11/5-FU combinations should be considered as "standard" first-line treatment in ACC.
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PMID:Irinotecan (CPT-11) in combination with infusional 5-fluorouracil and leucovorin (de Gramont regimen) as first-line treatment in patients with advanced colorectal cancer: a multicenter phase II study. 1182

We designed a phase II study of weekly irinotecan (CPT-11) and carboplatin for refractory or relapsed small cell lung cancer (SCLC) and assessed the response rate, survival, and toxicity. Twenty-nine patients with refractory or relapsed SCLC were entered onto the trial. The median time off chemotherapy was 3.5 months (range: 0.8-12.9). Patients were treated at 4-week intervals using CPT-11 (50 mg/m(2) intravenously on days 1, 8 and 15) plus carboplatin (AUC = 2 mg/ml min, intravenously on days 1, 8, 15). All patients were assessable for toxicity and survival; 28 patients were assessable for response. There were nine partial responses (PRs). Overall response rate was 31.0% (95% CI: 15.3-50.8%). The median time to progression was 3.5 months. Median survival time was 6.1 months. Major toxicity was myelosuppression. Grade 3 to 4 neutropenia and thrombocytopenia occurred in 52 and 21% of patients, respectively. Grade 3-4 diarrhea was observed in 7%. There was one treatment-related death due to febrile neutropenia and sepsis. This combination of CPT-11 and carboplatin seems to be active second-line regimen with acceptable toxicity against small cell lung cancer.
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PMID:Phase II study of weekly irinotecan and carboplatin for refractory or relapsed small-cell lung cancer. 1223 2

Standard chemotherapy in advanced colorectal carcinoma (CRC) has not yet been established. The present study was conducted to assess the efficacy and toxicity profile of CPT-11, leucovorin (LV), and bolus 5-fluorouracil (5-FU) in a weekly schedule. Fifty-five patients were entered with no prior chemotherapy for advanced disease or adjuvant treatment ended at least 6 months preceding study entry, and 45 were assessable for response. Patients were treated with CPT-11 80 mg/m2 (7 patients) or 70 mg/m2 (48 patients). After completion of CPT-11 infusion, LV 200 mg/m2 was administered over 2 hr followed immediately by 5-FU 450 mg/m2, IV bolus, weekly for 6 weeks followed by a 2-week rest period. Treatment was continued for four cycles. Because of grade 3 and 4 diarrhea in four of the first seven patients, the study was amended to reduce the starting dose of CPT-11 from 80 to 70 mg/m2 weekly. Four complete and 10 partial responses were observed (response rate: 25.5%), the median time to progression (TTP) was 7.7 months, 1-year survival rate was 62.3%, and the median overall survival was 15.0 months. Grade 3 and 4 diarrhea occurred in seven patients (12.7%), four of them treated with CPT-11 80 mg/m2. Grade 3 myelotoxicity occurred in five patients (9.0%). Toxic death because of diarrhea, neutropenia, bacteremia, and sepsis occurred in a patient treated with CPT-11 80 mg/m2. Our results confirm the efficacy of CPT-11, LV, and 5-FU in a weekly schedule in patients with advanced CRC. Further studies are needed to compare the present regimen with higher doses of CPT-11 with LV plus different schedules of 5-FU administration in the treatment of metastatic CRC.
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PMID:A phase II study with CPT-11 plus leucovorin and bolus IV 5-fluorouracil in patients with advanced colorectal carcinoma. 1473 89

A phase I study of irinotecan hydrochloride (CPT-11), carboplatin, and dexamethasone treatment in 7 patients with relapsed lymphoma and 7 patients with refractory lymphoma was conducted to evaluate the maximal tolerated dose. The 6 female and 8 male patients had a median age of 63 years (range, 45-73 years), a median performance status of 0 (range, 0-2), and a median disease stage of IV. This study included patients with diffuse large B-cell lymphoma (n = 5), adult T-cell leukemia/lymphoma (n = 2), mantle cell lymphoma (n = 2), follicular lymphoma (n = 2), angioimmunoblastic T-cell lymphoma (n = 1), anaplastic large cell lymphoma (n = 1), and Hodgkin's lymphoma (n = 1). All patients had received anthracycline-containing combination chemotherapy prior to this therapy. The starting dosage of CPT-11 was 15 mg/m2 per day (days 1-3 and 8-10), and dosage-escalation increments of 5 mg/m2 per day were planned, with fixed dosages of carboplatin (250 mg/m2 per day, day 1) and dexamethasone (40 mg/body, days 1-3 and days 8-10). Five patients were enrolled at level 1, 3 at level 2, 4 at level 3, and 2 at level 4. Ten patients (71%) and 11 patients (79%) experienced grade 3 or 4 hematologic toxicities of leukocytopenia and neutropenia, respectively. Three patients (29%) and 9 patients (64%) experienced grade 3 or 4 thrombocytopenia and anemia, respectively. Two patients who received 30 mg/m2 (level 4) of CPT-11 developed sepsis. We concluded that the recommended dose of CPT-11 with carboplatin and dexamethasone is 25 mg/m2. No deaths were related to this chemotherapy, and no patient developed liver dysfunction. The overall response rate was 36%. We conclude that the combination therapy of CPT-11, carboplatin, and dexamthasone is effective as salvage therapy but that the duration of response is too short.
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PMID:Phase I study of the combination of irinotecan hydrochloride, carboplatin, and dexamethasone for the treatment of relapsed or refractory malignant lymphoma. 1516 96

To compare irinotecan (CPT-11)+gemcitabine vs CPT-11 alone as second-line treatment for patients with advanced non-small cell lung cancer (NSCLC) progressing after docetaxel-cisplatinum-based therapy. A total of 147 evaluable, pretreated patients, with NSCLC, received either gemcitabine (1000 mg m(-2), days 1 and 8)+CPT-11 (300 mg m(-2), day 8) (Group A, n=76) or CPT-11 (300 mg m(-2), day 1) (Group B, n=71), every 3 weeks. All patients were evaluable for response and toxicity. The objective response rate was 18.4% (95% CI: 9.71-27.14%) and 4.2% (95% CI: 0-8.90%) (P=0.009) for groups A and B, respectively. No significant differences between the two groups in terms of the median duration of response, time to tumour progression, overall survival and 1-year survival were observed. The CPT-11/gemcitabine regimen significantly improved the patients' quality of life ('general mood today' (P=0.014), 'coughing' (P=0.003) and 'intensity of symptoms' (P=0.034)) compared with CPT-11. More cycles had to be delayed (P=0.001) and required prophylactic growth factor support (P=0.001) in Group A than B. Three (3.9%) patients in Group A and eight (11.3%) in Group B developed febrile neutropenia (P=0.09); one patient died of sepsis in each group. Three additional (Group A, n=1; Group B, n=2) treatment-related deaths were observed. Grade 3-4 haematologic toxicity was comparable in the two groups except anaemia (P=0.03 in favour of CPT-11). Other nonhaematologic toxicities were mild and similar in the two groups. CPT-11+gemcitabine resulted in a higher response rate and better control of disease-related symptoms than CPT-11 alone, but without any improvement in the overall survival.
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PMID:Irinotecan plus gemcitabine vs irinotecan for the second-line treatment of patients with advanced non-small-cell lung cancer pretreated with docetaxel and cisplatin: a multicentre, randomised, phase II study. 1523 86

When a male patient(age: 63)came to our hospital to report his discomfort in swallowing on February 16, 2005, we observed that a tumor of the subcircular type 2 had invaded his descending aorta directly, which was equivalent to the range from tracheal bifurcation to esophagogastric junction. At the same time, we found multiple metastases in lymph node which were from both cervixes to the range around the aorta abdominalis, and pleural effusion on both sides. We diagnosed them as small cell type undifferentiated esophageal carcinoma(T4N4M1, Stage IVb)with esophagus lesion. We started chemotherapy with irinotecan(CPT-11)and cisplatin(CDDP)in accordance with the guideline of the treatment for lung small cell carcinoma. Five days after we began the chemotherapy, leukopenia(grade 4)and abrupt bloody diarrhea were observed. Although we conducted intensive care, on day 7 he died of multiple organ failure caused by sepsis. Pathologic anatomy reported was necrosis of intestinal mucosa which ranged widely from his duodenum to rectum. We reported this fatal case of small cell type undifferentiated carcinoma of the esophagus caused by treatment with CPT-11, which triggered abrupt diarrhea and bloody discharge.
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PMID:[A fatal case of small cell type undifferentiated carcinoma of the esophagus with sudden diarrhea and bloody discharge by CPT-11]. 1893 79


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