Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027947 (neutropenia)
 17,527 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Irinotecan (CPT-II) is a semisynthetic derivative of camptothecin. It and other camptothecin analogues/derivatives appear to exert their antitumour activity by binding to topoisomerase I. The active metabolite of irinotecan, 7-ethyl-10-hydroxycamptothecin (SN-38), has demonstrated potent growth inhibition of human colorectal cancer cells in vitro, with superior activity to fluorouracil. In phase II clinical studies in patients with advanced colorectal cancer, objective response rates after irinotecan therapy ranged between 20.5 and 32%. These studies used a range of irinotecan regimens including 350 mg/m2 once every 3 weeks (Europe), 125 to 150 mg/m2 once a week for 4 weeks followed by a 2-week drug-free interval (US) and 100 mg/m2/week or 150 mg/m2 every 2 weeks (Japan). The median duration of response ranged between 5.6 and 10.6 months. Disease stabilisation occurred in 30 to 71.2% of patients. Objective response rates to irinotecan therapy in patients who had received no prior chemotherapy were similar to those in patients pretreated with fluorouracil. Importantly, irinotecan also induced responses in some patients with tumours refractory to fluorouracil. Severe (grade 3 or 4) neutropenia and diarrhoea, which occurred in up to 40% of patients receiving irinotecan therapy in phase II studies, require careful monitoring and appropriate management. Thus, irinotecan is a valuable agent for the second-line treatment of patients with advanced colorectal cancer who fail to respond to or relapse after fluorouracil therapy.
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PMID:Irinotecan. A review of its pharmacological properties and clinical efficacy in the management of advanced colorectal cancer. 889 70

In six published phase II trials, irinotecan (CPT-II; Camptosar; Pharmacia & Upjohn Co, Kalamazoo, MI) has demonstrated consistent activity with response rates of approximately 13% to 27% in patients with advanced colorectal cancer (CRC) refractory to 5-fluorouracil (5-FU) therapy. Similar response and median survival rates have been achieved using either the US regimen (once a week for 4 weeks followed by a 2-week rest) or the European regimen (once-every-3-week schedule). The optimal administration schedule for irinotecan is uncertain. Phase II evaluation of a biweekly administration schedule in a similar group of patients produced similar response rates. With all schedules tested, the most common toxicities remain delayed diarrhea, neutropenia, and nausea and vomiting. The most common toxicity, late diarrhea, can be ameliorated using high-dose loperamide. Irinotecan has been explored as a single agent in patients with newly diagnosed CRC and has generated response rates in the range of 19% to 32% and a median survival time of approximately 12 months, suggesting a level of antitumor activity similar to that observed with 5-FU and leucovorin. Two recently completed phase III studies in 5-FU-refractory patients have shown that treatment with irinotecan confers a survival advantage compared with treatment with infusional 5-FU or best supportive care. Current studies focus on the activity of irinotecan as part of combined chemotherapy in patients with newly diagnosed advanced-stage CRC, as part of combined-modality therapy with radiation therapy, and as adjuvant chemotherapy for patients with locally advanced CRC.
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PMID:Efficacy and toxicity of irinotecan in patients with colorectal cancer. 978 15

Irinotecan hydrochloride (CPT-11) is a topoisomerase I inhibitor with a broad antitumor spectrum. In the present study, we combined CPT-1 and mitoxantrone (MIT) with dexamethasone because the effect elicited by this combination was additive or better in a preclinical study. This study was performed to determine the efficacy and toxicities of this combination. Thirty-two patients were evaluable. CPT-11 combined with MIT achieved a complete remission in 11 patients (34.4%) and a partial remission in 9 patients (28.1%). The median follow-up period was 20 months. The 4-year survival rate was 31.8% (95% confidence intervals: 11.2-64.6%), and the 3-year event-free survival rate was 16.1% (95% confidence intervals: 8.2-24.6%). Grade 3 or higher hematological toxicity included neutropenia in 96.9%, anemia in 3.1%, and thrombocytopenia in 15.6%. Grades 1, 2, and 3 nonhematological toxicity included diarrhea in one patient, nausea/vomiting in five patients, and hematuria in one patient, respectively. CPT-11 combined with MIT was safe even for elderly patients and was effective even in patients who had received pretreatment with doxorubicin. In addition, this regimen can be used on an outpatient basis. This combination should be tested further to determine the optimum doses and administration schedule.
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PMID:Combination therapy with irinotecan (CPT-11), mitoxantrone, and dexamethasone in relapsed or refractory non-Hodgkin's lymphoma: a pilot study. 1152 67

The role of non-platinum combination chemotherapy in the treatment of advanced non-small-cell lung cancer (NSCLC) has not yet been clarified. In this phase I study, the dose-limiting toxicity (DLT), the maximum tolerable dose (MTD) and the antitumor activity of a two-drug combination of docetaxel (DCT) and irinotecan (CPT) in patients with advanced NSCLC were evaluated. Previously untreated patients with NSCLC in stage IIIB with malignant pleural effusion or stage IV were eligible. Both drugs were administered by 1-h intravenous infusion on day 1, and repeated every 3 weeks. DCT was given before CPT administration. Five escalating dose levels of DCT/CPT (40/135, 50/135, 50/150, 60/150, and 60/165 mg/m2) were studied. Eighteen patients received 44 courses. The DLT was considered to be neutropenia, because grade 4 neutropenia lasting for 3 days or more was observed in three patients, which was accompanied with three episodes of febrile neutropenia. As a non-hematological toxicity, grade 3 diarrhea occurred in three patients. Since all the three patients treated at the fifth dose level (DCT at 60 mg/m2 and CPT at 165 mg/m2) experienced DLT (grade 4 neutropenia in two patients and grade 3 hepatic toxicity in one), this dose level was determined to be the MTD. The objective response rate was 33.3%, and the median survival time was 13.6 months. To confirm the effectiveness of this combination for advanced NSCLC which was suggested in the present study, a phase II study with the recommended doses (150 mg/m2 for CPT and 50-60 mg/m2 for DCT) is warranted.
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PMID:Phase I study of docetaxel and irinotecan in patients with advanced non-small-cell lung cancer. 1519 38

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

We conducted a phase II study of combination chemotherapy with nedaplatin (NP) with irinotecan (CPT) to determine the effects against unresectable non-small cell lung cancer (NSCLC) and to determine the qualitative and quantitative toxicities of this combination chemotherapy in 70 years or older patients. Thirty-eight patients received 100 mg/m2 NP on day 1 and 60 mg/m2 CPT on days 1 and 8 every four weeks. Twenty-five patients achieved PR, nine SD and three PD, and the overall response rate was 65.8%. Nineteen patients (50%) experienced grade 4 neutropenia. Neutropenic fever occurred in 11 patients (29%) and one of them died. Of other grade 3 non-hematologic toxicities, two patients experienced diarrhea; one interstitial pneumonitis; one liver injury; and one rash. The median survival time was 418 days and the one-year survival rate was 55.3%. In conclusion, NP combined with CPT is an active treatment for elderly patients with NSCLC.
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PMID:Phase II study of nedaplatin and irinotecan for elderly patients with advanced non-small cell lung cancer. 1584 64

The 3-drug regimen of CPT-11+5-FU+l-LV is generally used for metastatic and/or recurrent colorectal cancer. We have applied this treatment as the first-line intervention in our hospital. However,when the efficacy is reduced we try chemotherapy using CPT-11+TS-1 for 5 outpatients as second- or third-line chemotherapy. Decreased CEA levels were subsequently observed in 4 of 5 cases. In addition, 2 cases exhibited grade 1 or 2 adverse effects, but no case developed neutropenia. We could expect such effects even for patients after only 5-FU, and this treatment may be performed safely on ambulatory patients.
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PMID:[Second-or third-line chemotherapy with CPT-11+TS-1 for 5 cases of metastatic and recurrent colorectal cancer]. 1743 54

We retrospectively analyzed the outcome of high-risk patients with non-small cell lung cancer (NSCLC) treated with nedaplatin (NP) and irinotecan (CPT) combination chemotherapy. Between July 2002 and January 2006, 31 NSCLC patients with multiple high-risk factors were treated with NP at 50 mg/m2 and CPT at 50 mg/m2 on days 1 and 8 every 4 weeks. Among them, the patients had a total of 85 risk factors, including poor performance status (2 or 3) in 27, cardiac or pulmonary failure in 15, symptomatic bone or brain metastasis in 9, and advanced age (> or = 75 years) in 8, as well as other factors. A total of 83 courses of the chemotherapy were administered and 24 patients were able to receive 2 to 4 courses. With regard to toxicities, 7 (8.4%) and 11 courses (13%) were associated with grade 4 neutropenia and grade 3 febrile neutropenia, respectively. One patient suffered acute myocardial infarction. Each of the toxicities was controllable and there were no treatment-related deaths. One patient achieved CR, 13 achieved PR, 14 SD and 3 PD, and the overall response rate was 45.2%. Of 26 patients with stage IIIB or IV, the median survival time was 232 days, the 1-survival rate was 38.5%, and 3 patients survived for more than 3 years. In conclusion, chemotherapy with NP and CPT appears to be safe and highly effective for high-risk patients with NSCLC.
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PMID:Feasible combination chemotherapy with nedaplatin and irinotecan for patients with non-small cell lung cancer and multiple high-risk factors. 1755 65

A 69-year-old female patient with type 2 advanced gastric cancer (s-T4N0M0H0Cy0P0, f-Stage IIIA) located from lower corps to antrum underwent a distal gastrectomy with D2 lymphandectomy in May 2006. After surgical treatment, S-1+ docetaxel combined chemotherapy was started for pEM (+) due to direct invasion to pancreas head as the first-line chemotherapy. However, the local recurrence whose diameter was 24 mm at pancreas head was detected with enhanced CT in December 2006. Moreover, nevertheless CPT-11+CDDP combined chemotherapy or paclitaxel monotherapy as the second or the third-line chemotherapy, respectively, the diameter of the local recurrence enlarged to 38 mm in November 2007. Therefore, chemo-radiotherapy using with S-1 and CDDP was started in December 2007 and the diameter of local recurrence was reduced to 25 mm in January 2008. No adverse event of grade 3 or more occurred during chemo-radiotherapy except for grade 3 of neutropenia. Chemo-radiotherapy for this gastric-cancer patient with local recurrence of multiple anti-tumor drug resistance was effective and safe.
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PMID:[A case of advanced gastric cancer treated with chemo-radiotherapy as the fourth-line therapy]. 1910 21

SN-38, an active metabolite of irinotecan (CPT-11), is glucuronidated into SN-38G mainly by UGT1A1, during detoxification. However, significant interindividual pharmacokinetic variability in SN-38 is caused by factors, including inherited predispositions that may affect the function and expression of UGT1A1. Moreover, these individual differences can contribute to the development of clinical conditions, such as severe leucopenia and diarrhea. Similar to SN-38, bilirubin is excreted into bile after being glucuronidated by UGT1A1. Thus, bilirubin is metabolized by a mechanism similar to that of SN-38. This suggests that the bilirubin level may be an indicator of the adverse effects caused by CPT- 11. On the other hand, the ratio between the AUC of SN-38 and the AUC of SN-38G (AUCSN-38/AUCSN-38G) indicates the ability of SN-38 to be glucuronidated, and is known to correlate with leucopenia and diarrhea. However, many blood sampling points are required to calculate these AUCs. Therefore, the daily estimation of the AUCSN-38/AUCSN-38G values of individual patients is not practical at the clinical level. Thus, the objectives of this study were as follows: (1) to establish whether or not the total bilirubin level is a useful indicator in predicting the development of CPT-11 toxicity. (2) to investigate the correlation of SN-38/SN-38G (the ratio of the serum concentrations of SN-38 and SN-38G) with AUCSN-38/AUCSN-38G. Based on the result of this investigation, it will be discussed whether or not SN-38/SN-38G may be used as an alternative to AUCSN-38/AUCSN-38G. This study included 14 patients with small cell lung cancer or non-small-cell lung cancer, in whom serum concentrations of CPT-11, SN-38, and SN-38G were measured by HPLC. The results demonstrated a significant correlation between the total bilirubin levels prior to chemotherapy and the logarithmic values for AUCSN-38/AUCSN-38G (r2=0.852). Among the cases with high values for both the total bilirubin level and the AUCSN-38/AUCSN-38G ratio, none of the patients had grade-3 diarrhea, while many cases tended to have grade-3 to -4 neutropenia. Additionally, the results of regression analysis suggest that SN-38/SN-38G (2 hr) and SN-38/SN-38G (4 hr) might be preferable as a predictive index for AUCSN-38/AUCSN-38G. These findings suggest that the total bilirubin level and SN-38/SN-38G, 2 to 4 hours after administration might be used as indicators to predict CPT-11-induced neutropenia. These indicators are likely to contribute to the pharmacogenetic analysis of UGT1A1 genes, as well as individualized therapy, in future, and further studies on this subject are expected.
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PMID:[Assessment of total bilirubin or SN-38/SN-38G ratio as a predictor of severe irinotecan toxicity]. 1975 21


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