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

New agents with improved systemic activity are needed for the treatment of lung cancer. Irinotecan (Camptosar) is a promising agent in advanced non-small-cell (NSCLC) and small-cell lung cancer (SCLC). In a Japanese phase III trial of advanced NSCLC, irinotecan or irinotecan/cisplatin demonstrated a significant survival advantage compared to the standard of vindesine/cisplatin. Similar North American phase III trials focusing on irinotecan's role in NSCLC are under way. Ongoing trials have also been launched to corroborate the significant survival advantage reported by a Japanese phase III trial for irinotecan/cisplatin vs standard etoposide/cisplatin in extensive SCLC. Current and planned trials in NSCLC with irinotecan in combination with gemcitabine (Gemzar), the taxanes, and other new agents, and thoracic radiotherapy should also provide useful clinical data. Moreover, trials in SCLC are investigating the rationale of combining irinotecan with a platinum agent as a component of chemoradiotherapy regimens. Promising data from these and other studies will further elucidate a role for irinotecan in the management of lung cancer.
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PMID:Irinotecan in advanced lung cancer: focus on North American trials. 1525 64

Locally advanced non-small-cell lung cancer represents 30% to 40% of all pulmonary malignancies. Most patients will die of the disease after aggressive contemporary treatments. Therefore, significant improvement in therapeutic methods must be implemented to improve overall survival rates. The arrival of a new generation of chemotherapeutic agents--including the taxanes, gemcitabine (Gemzar), and topoisomerase inhibitors such as irinotecan (Camptosar) and topotecan (Hycamtin)--offers the hope of significant advances in the treatment of lung cancer. Irinotecan and topotecan are camptothecin derivatives that inhibit topoisomerase I enzyme. It is believed that topoisomerase I inhibitors stabilize a DNA/topoisomerase I complex and interact with replication machinery to cause cell death. A significant amount of data demonstrates that these topoisomerase I inhibitors also act as radiosensitizers. With the increasing data that support concurrent chemoradiation treatment for malignancies, including lung cancer and head and neck cancers, there is an impetus to pursue the additional drugs that may potentially improve local control and survival. Irinotecan is undergoing early clinical trials in the combined-modality setting in several different disease sites. This paper will review the data on the role of camptothecin derivatives as a radiosensitizer and as a component of combined-modality therapy for lung cancer. It is hoped that newer treatment strategies, like the combination of radiation and topoisomerase I inhibitors, will have a significant impact on cure rates in the future.
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PMID:Topoisomerase I inhibitors in the combined-modality therapy of lung cancer. 1525 65

Irinotecan (CPT-11) has been shown to exhibit excellent antitumour activity against small-cell lung cancer (SCLC). A multi-institutional phase II study was therefore conducted to evaluate the efficacy and toxicity of CPT-11 combined with cisplatin (CDDP) and etoposide (ETOP) (PEI regimen) for the treatment of sensitive relapsed SCLC. Patients who responded to first-line chemotherapy but relapsed more than 8 weeks after the completion of first-line therapy (n=40) were treated using the PEI regimen, which consisted of CDDP (25 mg m(-2)) weekly for 9 weeks, ETOP (60 mg m(-2)) for 3 days on weeks 1, 3, 5, 7, and 9, and CPT-11 (90 mg m(-2)) on weeks 2, 4, 6, and 8 with granulocyte colony-stimulating factor support. Five complete responses and 26 partial responses were observed, and the overall response rate was 78% (95% confidence interval 61.5-89.2%). The median survival time was 11.8 months, and the estimated 1-year survival rate was 49%. Grade 3/4 leucocytopenia, neutropenia, and thrombocytopenia were observed in 55, 73, and 33% of the patients, respectively. Nonhaematological toxicities were mild and transient in all patients. In conclusion, the PEI regimen is considered to be highly active and well tolerated for the treatment of sensitive relapsed SCLC.
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PMID:Multi-institutional phase II trial of irinotecan, cisplatin, and etoposide for sensitive relapsed small-cell lung cancer. 1528 Sep 19

Standard first-line chemotherapy for the majority of patients with advanced non-small-cell lung cancer (NSCLC) consists of platinum-based combination regimens including one of the newer-generation agents, such as gemcitabine (Gemzar), a taxane, vinorelbine (Navelbine), or irinotecan (Camptosar). Several effective regimens are available, the choice of which will depend on treatment goals, individual patient or disease factors, as well as physician preferences. This paper surveys randomized trials of many of the newer-generation chemotherapy combinations in patients with advanced NSCLC to examine several issues, such as which new-generation regimen to use, whether a platinum agent is needed, the optimal number of drugs in the combination, and treatment duration.
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PMID:Current paradigms in first-line treatment of non-small-cell lung cancer. 1533 54

The 1-year survival for patients with metastatic non-small-cell lung cancer is only around 35%. We are evaluating the combination of irinotecan (Camptosar) and carboplatin (Paraplatin) in patients with stage IIIB and IV non-small-cell lung cancer. The first five patients received irinotecan, 250 mg/m2 over 90 minutes followed by carboplatin at an area under the concentration-time curve of 5 over 1 hour1 The dose of irinotecan was subsequently 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 42 patients, 37 have been enrolled so far. Of the 37 enrolled patients, 25 received at least two cycles, 20 received at least four cycles, and 12 received all six planned cycles. Grade 4 neutropenia (absolute neutrophil count <500) occurred in 10 patients and 19 treatment cycles. Two of these patients also had grade 4 diarrhea. Thirty-six cycles (30%) were delayed for neutropenia, six of which occurred among the first five patients who received irinotecan at 250 mg/m2. Best response to therapy included 7 partial responses (23%), 11 stable disease (37%), with 12 patients having progressive disease (40%). The regimen of irinotecan and carboplatin administered once every 3 weeks is tolerable and convenient, with early evidence of activity. 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 NSCLC: an update. 1568 28

Among patients with lung cancer, approximately 15% have small-cell lung cancer (SCLC). Although, without therapy, untreated SCLC is a rapidly proliferating tumor with a poor prognosis, response rates to chemotherapy and radiotherapy are high. SCLC is usually staged as either limited disease or extensive disease. Extensive disease is treated primarily with chemotherapy. A recent Japanese randomized trial compared IP (irinotecan [Camptosar]/cisplatin [Platinol]) with EP (etoposide/cisplatin). Patients in the IP arm had significantly better outcomes than patients in the EP arm. In the IP arm, the response rate was 84%, and the median overall survival period was 12.8 months. Limited disease is usually treated with concurrent chemotherapy and accelerated radiation therapy, and approximately 20% of patients are cured. Further investigations to improve local control and inhibit distant metastasis are clearly warranted. The dose-rate escalation in radiotherapy (administered concurrently with chemotherapy) is important in improving local control, and the introduction of molecular-targeting agents is necessary to inhibit distant metastasis.
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PMID:Small-cell lung cancer: current therapy and novel agents. 1574 51

Irinotecan is a topoisomerase I inhibitor that is highly active against small cell lung cancer (SCLC). Etoposide is another drug that is effective for SCLC. Since combination of these two topoisomerase inhibitors revealed a synergistic effect in vitro and showed a safety in phase I study, we conducted a phase II study in patients with previously un-treated extensive disease (ED) SCLC to evaluate the efficacy and toxicity of this combination. Fifty patients with previously untreated ED-SCLC were enrolled. Irinotecan was administered intravenously at 60mg/m(2) on days 1, 8, and 15, while etoposide was given at 80mg/m(2) on days 2-4. Treatment was repeated every 4 weeks for four cycles. The overall response rate was 66.0%, with a complete response rate of 10.0%. The median survival time was 11.5 months and the 1- and 2-year survival rates were 43.2 and 14.4%, respectively. The major toxicity of this regimen was myelosuppression, including grade 3 or 4 neutropenia (62.9%), leukopenia (28.0%), and anemia (14%). The other grade 3 toxicity was diarrhea (2%). This irinotecan and etoposide regimen is active against ED-SCLC with relatively mild toxicity.
Lung Cancer 2005 Aug
PMID:Irinotecan and etoposide for previously untreated extensive-disease small cell lung cancer: a phase II trial of West Japan Thoracic Oncology Group. 1602 21

Irinotecan/cisplatin (IP) is an active regimen for extensive-disease small-cell lung cancer (ED-SCLC). However, the optimal dose/schedule is unsettled. To evaluate the efficacy and safety of a dose-intensified, weekly concomitant administration of IP, we conducted a phase II study in chemo-naive patients with ED-SCLC. Between October 2001 and February 2004, 37 patients were enrolled. Twenty-nine (78%) were male, 21 (57%) had ECOG PS 0 or 1, and the median age was 62 yr. The initial six patients received cisplatin 50 mg/m2 followed by irinotecan 90 mg/m2 iv on d 1 and 8 of a 21-d cycle (dose level I), with one treatment-related death, three febrile neutropenias. Thereafter, the doses of cisplatin and irinotecan were reduced to 40 mg/m2 and 80 mg/m2, respectively (dose level II). The treatment was continued for up to six cycles. The overall response rate was 97%, with a complete response (CR) rate of 26%. The median duration of response was 6.4 mo (range, 1.6-13.1 mo). At a median follow-up of 27.3 mo, the median survival time was 11.1 mo and 1- and 2-yr survival rates were 44.1% and 11.8%, respectively. The median progression-free survival (PFS) was 6.0 mo (range, 1.5-13.1 mo) and 1-year PFS rate was 7%. Major grade 3 or 4 toxicities included neutropenia (89%), anemia (59%), and diarrhea (27%). Despite of significant myelosuppresion, this dose-intensified weekly concomitant administration of cisplatin and irinotecan was feasible. This dose-schedule showed promising activity with high rate of complete remission in patients with ED-SCLC.
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PMID:A phase II study of dose-intensified weekly concomitant administration of cisplatin and irinotecan in chemonaive patients with extensive-disease small-cell lung cancer. 1611 Jan 39

Our purpose was to determine the efficacy of irinotecan plus paclitaxel administered on day 1, repeated every 2 weeks, in untreated patients with advanced or metastatic non-small-cell lung cancer (NSCLC). In total, 56 patients with inoperable or metastatic stage III and IV NSCLC with a histologically or cytologically confirmed diagnosis were enrolled. None of the patients had undergone prior chemotherapy or radiation therapy. Treatment involved irinotecan 125 mg m(-2) and paclitaxel 135 mg m(-2) administered on day 1 and repeated every 2 weeks for a planned number of nine cycles. With a standard dose of paclitaxel at 135 mg m(-2), the dosage of irinotecan was escalated at four levels: 75, 100, 125 and 150 mg m(-2); 125 mg m(-2) was established as the maximum tolerated dose; this dosage was administered to 46 patients. A total of 52 patients (median age 65 years, range 38-77 years) were assessable for toxicity and survival and 46 for response rate. Out of 46 evaluable patients, 19 achieved partial response (41.3%), 17 had stable disease (37%) and 10 (21.7%) experienced disease progression. The median duration of response was 6 months (range 2-9+ months). The main adverse reactions were myelotoxicity (grades 3 and 4) in 10 (19.2%) patients and diarrhoea (grade 3) in four (7.7%) patients. Irinotecan combined with paclitaxel, administered every 2 weeks, appears to be an effective treatment for advanced-stage NSCLC.
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PMID:Front-line paclitaxel and irinotecan combination chemotherapy in advanced non-small-cell lung cancer: a phase I-II trial. 1625 79

Irinotecan has recently been found to be one of the most active agents in the treatment of small-cell lung cancer (SCLC). Japanese investigators have led the way in the early investigation of irinotecan, and multiple studies are now ongoing in the United States. In a phase II trial conducted by the West Japan Thoracic Oncology Group, irinotecan was associated with a median survival of 13 months in patients with extensive-stage disease. Subsequently, the Japanese Clinical Oncology Group completed a phase III trial comparing irinotecan plus cisplatin to cisplatin and etoposide. In this study, median, 1-year, and 2-year survival rates were superior with irinotecan and cisplatin. Two confirmatory phase III trials are in progress in the United States. Based on these early data, it is likely that irinotecan and a platinum agent will prove to be at least as effective as any other treatment for patients with extensive-stage SCLC. Investigators have embarked on combining irinotecan with carboplatin in anticipation that this will be a preferable treatment. Phase I/II trials are complete and the doses and schedules have been recommended. As a result, we are currently exploring irinotecan and carboplatin in phase II trials in both extensive- and limited-stage settings. In addition, several of the newer biologic targeted agents are being tested in SCLC in combination with newer chemotherapy regimens. The results from these trials are eagerly awaited.
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PMID:Evolving role of irinotecan in small-cell lung cancer. 1625 36


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