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Query: UMLS:C0242379 (lung cancer)
 71,905 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Lung cancer is the leading cause of cancer-related death in the United States. There was rapidprogress in the treatment of lung cancer duringpast decades, but local control and survival rates are still poor. Radiation therapy has been an indispensable part of the management of lung cancer, and a recent paradigm is concurrent chemoradiation therapy. Many novel chemotherapeutic agents were recently developed to improve both local and systemic control of cancer, including camptothecin derivatives, which are topoisomerase I inhibitors. Irinotecan (CPT-11, Camptosar) is a semisynthetic water-soluble derivative of camptothecin. Irinotecan is active as a single agent against lung cancer, and is also a potent radiosensitizing agent in human lung cancer cell lines and xenografts. There have been many phase I and II clinical trials demonstrating promising results of single-agent irinotecan and combination with concurrent therapy. This article reviews irinotecan's mechanism of action of cytotoxicity and of radiation-sensitizing effects, as well as recent clinical data regarding combining radiation therapy and irinotecan for both non-small-cell and small-cell lung cancer.
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PMID:Irinotecan in combination with radiation therapy for small-cell and non-small-cell lung cancer. 1237 96

For more than 2 decades, combination chemotherapy has been the standard treatment for patients with small-cell lung cancer. Despite high initial response rates in both extensive- and limited-stage disease, long-term survival rates are only 10% to 20%. Camptothecins and taxanes are newer classes of agents that have shown significant activity against small-cell lung cancer. Their incorporation into chemotherapy regimens for small-cell lung cancer is being actively studied. In one randomized multicenter study, patients with advanced small-cell lung cancer treated with irinotecan (CPT-11, Camptosar) and cisplatin had a better survival time than patients receiving standard therapy. The combination of taxanes and irinotecan holds promise as an active regimen that may be tolerated better than cisplatin and irinotecan.
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PMID:Camptothecin and taxane regimens for small-cell lung cancer. 1237 99

The DNA topoisomerase inhibitor irinotecan (CPT-11, Camptosar) is being evaluated as a novel chemotherapeutic agent for small-cell lung cancer that may complement other agents and treatment modalities. Combination chemotherapy is recognized as the most effective means of improving survival in patients with extensive-stage small-cell lung cancer, but until recently, no one combination had emerged as superior. In a recent Japanese phase III study, irinotecan in combination with cisplatin significantly improved survival of previously untreated patients with extensive small-cell lung cancer compared with standard etoposide/cisplatin therapy (median progression-free survival: 6.9 vs 4.8 months, P < .001; median overall survival: 12.8 vs 9.4 months, P = .0021). Two additional phase III trials are planned to confirm these results in the United States, and to investigate how the irinotecan/cisplatin administration schedule may be modified to improve therapeutic index. This article will review the use of irinotecan in combination with cisplatin in patients with small-cell lung cancer.
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PMID:Irinotecan plus cisplatin in small-cell lung cancer. 1237

Lung cancer remains the primary cause of cancer-related death in both men and women in the United States. Chemotherapy has been shown to provide a survival benefit in patients with advanced non-small-cell lung cancer (NSCLC), and current regimens have produced median survivals of approximately 8 months and 1-year survival rates of 30% to 35% in patients with stage IIIB and IVdisease. Nevertheless, there remains room for improvement. Irinotecan (CPT-II, Camptosar) has demonstrated efficacy in the treatment of small-cell lung cancer (SCLC). It also appears to have promising activity in advanced NSCLC, producing overall response rates of up to 32%. Combinations of irinotecan and cisplatin or carboplatin (Paraplatin) have resulted in overall response rates of 25% to 56% in phase II and III studies in patients with advanced disease, with median survivals ranging from 9 to 13 months and 1-year survival rates of 33% to 58%. Current irinotecan-based doublet and triplet regimens appear to produce promising response rates with manageable toxicities. In addition, irinotecan has demonstrated potential as a radiosensitizing agent and is currently being evaluated in several trials of combined-modality therapy in patients with locally advanced NSCLC. Early trials of irinotecan in combination with cisplatin or carboplatin along with radiation therapy have reported overall response rates of 60% to 67%. The approach appears to have potential and warrants further study.
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PMID:Current role of irinotecan in the treatment of non-small-cell lung cancer. 1238 Sep 45

The purpose of this study was to evaluate the efficacy and tolerance of combined irinotecan and vinorelbine in previously treated patients with stage IIIB and IV non-small-cell lung cancer (NSCLC). Thirty-three patients with NSCLC (7 stage IIIB and 26 stage IV) were enrolled. All had been previously treated with cisplatin, paclitaxel, and gemcitabine as first-line chemotherapy. In addition, 24 patients had received radiotherapy. Irinotecan (300 mg/m(2)) was administered on day 1 and vinorelbine (30 mg/m(2)) on days 1 and 14, every 4 weeks. Partial response was achieved in 3 patients (9%; 95% CI: 2-24%), stable disease (SD) in 13 (39%; 95% CI: 23-58%), whereas 17 patients progressed (51%; 95% CI: 33-69%). Median event-free survival was 10 weeks and median overall survival was 25 weeks. Three patients were event free at the end of the study with a follow-up of 40, 73, and 75 weeks. Toxicity was mild, with leukopenia grade III-IV in 8.6% of cycles. No episodes of diarrhea III-IV were observed. Three patients died early after administration of this combination, one of them in the context of severe leukopenia and thrombocytopenia. Approximately 50% of patients treated with CPT-11 and vinorelbine in combination show partial response or stable disease with minimal toxicity.
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PMID:Second-line chemotherapy with irinotecan and vinorelbine in stage IIIB and IV non-small-cell lung cancer: a phase II study. 1239 89

A novel schema of intrapatient dose escalation was applied to determine a population-based maximum tolerated dose (pMTD) for irinotecan (CPT-11, Camptosar) and carboplatin (Paraplatin) in a phase I trial. A total of 74 patients with advanced solid tumors were enrolled with the following characteristics: men/women, 46/28; median age, 61 years; 51 patients with and 23 patients without prior chemotherapy; performance status of 0-1 (93%) and 2 (7%). Patients were started at dose level 1 with irinotecan at 200 mg/m2, and carboplatin at an area under the concentration-time curve (AUC) of 5 mg/mL x min, administered every 21 days. Depending on degree of toxicity observed, the dose for each patient in each subsequent cycle was determined according to a predetermined schema of dose levels. Individual maximum tolerated dose (iMTD) was determined for each patient. The pMTD was defined as the highest dose level for which the incidence of dose-limiting toxicity occurred in less than 33% of the patient population. The most common dose-limiting toxicity included neutropenia (58%), thrombocytopenia (15%), diarrhea (8%), and nausea/emesis (7%). The iMTD ranged from dose level-3 (irinotecan at 100 mg/m2 and carboplatin at an AUC of 4) to dose level 5 (irinotecan at 350 mg/m2 and carboplatin at AUC 6). The pMTD was determined to be dose level-1 and 1 for previously chemotherapy-treated and--untreated patients, respectively. Fifty-nine patients were assessable for response. Of note, a response rate of 40% was observed in 15 patients with relapsed small-cell lung cancer previously treated with platinum-based therapy. We recommend dose level 1 of irinotecan (200 mg/m2) and carboplatin (AUC 5) for chemotherapynaive patients, and dose level-1 of irinotecan (150 mg/m2) and carboplatin (AUC 5) for chemotherapy-treated patients in phase II trials.
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PMID:Population-based maximum tolerated dose of irinotecan and carboplatin. 1288 68

Irinotecan (CPT-11, Camptosar) has significant activity in small-cell lung cancer. In addition, preclinical models have demonstrated synergy between irinotecan and two standard front-line drugs for small-cell lung cancer: cisplatin and etoposide; phase III data also show significant survival benefit for irinotecan/cisplatin compared to standard treatment. These data suggest a potential clinical advantage to combining etoposide, cisplatin, and irinotecan as first-line therapy for small-cell lung cancer. The purpose of this phase I study was to establish if alternating weekly therapy with irinotecan/cisplatin and etoposide/cisplatin was tolerated and to determine the maximum tolerated dose of these agents in patients with small-cell lung cancer. Patients generally tolerated the weekly alternating chemotherapy with irinotecan/cisplatin and etoposide/cisplatin well, and this combination possessed significant antitumor activity in small-cell lung cancer.
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PMID:Dose-dense therapy with a novel irinotecan regimen for small-cell lung cancer. 1288 69

Recent findings indicate significant prolongation of survival and time to disease progression with irinotecan (CPT-11, Camptosar)/cisplatin vs etoposide/cisplatin in extensive-stage small-cell lung cancer, and a larger-scale phase III trial has been planned to provide more definitive data on the benefits of the irinotecan/cisplatin combination in this setting. Early-phase studies indicate that the activity of carboplatin (Paraplatin) in small-cell lung cancer is comparable to that of cisplatin, and that combining irinotecan on a day 1 and 8 schedule with split-dose carboplatin is feasible. Inhibition of the cyclooxygenase-2 (COX-2) enzyme, which is active in tumorigenesis, may augment efficacy and reduce toxicity of platinum/irinotecan combinations. A phase II trial has been designed to compare irinotecan/carboplatin and irinotecan/cisplatin combinations with or without the COX-2 inhibitor celecoxib (Celebrex) in patients with extensive-stage small-cell lung cancer. Results of these trials will help define the roles of platinum/irinotecan combinations and COX-2 inhibition in treatment for small-cell lung cancer.
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PMID:Irinotecan, cisplatin/carboplatin, and COX-2 inhibition in small-cell lung cancer. 1288 70

The outcome of patients with metastatic lung cancer is poor, with a 1-year survival rate of approximately 35%. We are evaluating the combination of irinotecan (CPT-11, Camptosar) and carboplatin (Paraplatin) in patients with stage IIIB and IV non-small-cell lung cancer. Eligible patients include those with histologic or cytologic diagnosis of non-small-cell lung cancer; no previous chemotherapy for metastatic lung cancer; and Eastern Cooperative Oncology Group performance status 0 or 1. The first five patients received irinotecan at 250 mg/m2 over 90 minutes followed by carboplatin at an area under the concentration-time curve (AUC) of 5 over 1 hour. Subsequently, the dose of irinotecan was reduced to 200 mg/m2 in view of febrile neutropenia in one of five patients. Chemotherapy cycles are repeated every 21 days. Patients are reevaluated every two cycles. Of a planned 37 patients, 14 have been enrolled and 9 are evaluable for toxicity and response at the time of this report. Thirty-two cycles have been administered, with seven 1-week delays and two dose reductions. To date there have been two partial responses and five patients with stable disease; two patients developed progressive disease on therapy. One patient had neutropenic fever; other toxicities included mild pancreatitis (n = 1) and diverticulitis (n = 1). The regimen of irinotecan and carboplatin administered once every 3 weeks demonstrates early evidence of activity, and is tolerable and convenient. The main toxicity is hematologic. This study is ongoing and actively accruing patients.
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PMID:Irinotecan and carboplatin in metastatic or recurrent non-small-cell lung cancer. 1288 71

Lung cancer is the most lethal malignancy in the United States. In light of its natural history, new agents with improved systemic activity are needed. Irinotecan (CPT-11, Camptosar) is a promising agent in the treatment of advanced non-small-cell and small-cell lung cancer. In subgroup analysis of a Japanese phase III trial, irinotecan or irinotecan/cisplatin demonstrated a significant survival advantage compared with standard vindesine (Eldisine)/cisplatin in advanced non-small-cell lung cancer. Similar North American phase III trials focusing on irinotecan's role in non-small-cell lung cancer are planned. Ongoing trials have also been inaugurated to corroborate the significant survival advantage reported by a Japanese phase III trial of irinotecan/cisplatin vs standard etoposide/cisplatin in extensive small-cell lung cancer. Current and planned trials in patients with non-small-cell lung cancer will investigate treatment using irinotecan in combination with gemcitabine (Gemzar), the taxanes, and other new agents, as well as with thoracic radiotherapy. Moreover, trials in small-cell lung cancer are investigating the utility of irinotecan in combination with a platinum agent when incorporated in chemoradiotherapy regimens. It is hoped that data from these and other studies will help investigators to more clearly delineate a role for irinotecan in the management of lung cancer.
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PMID:The global role of irinotecan in the treatment of lung cancer: 2003 update. 1288 72


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