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

More than one third of all non-small-cell lung cancer (NSCLC) patients present with advanced stage IV disease with metastases or with stage IIIB disease with a malignant pleural or pericardial effusion. The prognosis for these patients remains poor despite some improvement in survival produced by 2-drug chemotherapy combinations. With the best 2-drug combinations, the expected median survival is 8-9 months and > 80% of patients die within 2 years of diagnosis. The overall response rate to the best combination is < 40% and the complete response rate is only 1%. Clearly, superior therapies are needed. The topoisomerase I inhibitors have been developed because the topoisomerase I enzyme plays a critical role in the DNA repair process. Irinotecan is a topoisomerase I inhibitor developed during the 1990s. It was initially approved in the United States for the treatment of colorectal cancer. In early trials, considerable activity was seen in both small-cell lung cancer and NSCLC. These observations led to combination studies with cisplatin. Cisplatin-based therapy had become a standard approach in both stage IV disease and in combination with chest radiotherapy in stage IIIB disease because metaanalyses of randomized trials showed that cisplatin-based therapy significantly improved survival. Randomized trials also showed that cisplatin-based therapy improved symptoms in the majority of patients and improved quality of life. In early combination studies, the irinotecan/cisplatin combination produced responses in an average of 40% of patients and produced median survival times that averaged about 10 months. In randomized trials comparing irinotecan/cisplatin to vindesine/cisplatin, the irinotecan/cisplatin combination was slightly better than irinotecan alone and vindesine/cisplatin. These encouraging results led to ongoing randomized trials comparing the 2-drug combination of irinotecan/cisplatin to other 2-drug combinations. Irinotecan has also been combined safely and effectively with carboplatin. The 2-drug combination of irinotecan/carboplatin produced results similar to those achieved with irinotecan/cisplatin. Irinotecan has also been incorporated into 3-drug combinations such as irinotecan/carboplatin/paclitaxel with encouraging results. A randomized trial comparing docetaxel/irinotecan to docetaxel/cisplatin showed similar results. Randomized trials comparing the 3-drug combination to a 2-drug combination are in progress. The irinotecan/cisplatin combination has considerable activity in the second-line setting. Randomized trials comparing this combination to docetaxel are needed. Irinotecan is an active agent in the first- and second- line therapy of NSCLC.
Clin Lung Cancer 2002 Nov
PMID:The role of irinotecan combined with Cisplatin or Carboplatin in the treatment of advanced non-small-cell lung cancer. 1465 34

Although conventional therapies can produce median survival times of 8 months to 1 year in non-small-cell lung cancer (NSCLC) patients, there is still much room for improvement. With the emergence of multiple new agents, there is an increased number of therapeutic options available. Irinotecan has demonstrated activity in small-cell lung cancer and promising overall response rates of up to 35% as a single agent in NSCLC. Irinotecan/paclitaxel is currently being tested in a phase II trial with encouraging preliminary results. The triplet irinotecan/carboplatin/paclitaxel has been tested in a phase II trial as well. This triplet combination has yielded an impressive median survival time of 12.5 months and a 1-year survival rate of 50%, suggesting that this treatment regimen should be further explored. When used in combination with docetaxel, irinotecan has demonstrated comparable survival and response rates to the conventional cisplatin/docetaxel doublet but with lower toxicities. Ongoing and future trials will further clarify the role of irinotecan/taxane combinations in the treatment of NSCLC, both in treatment-naive patients and in the second-line setting.
Clin Lung Cancer 2002 Nov
PMID:Irinotecan/Taxane combinations in advanced non-small-cell lung cancer. 1465 35

Irinotecan possesses significant single-agent activity in non-small-cell lung cancer (NSCLC) and is active in combination with either cisplatin or carboplatin. Two phase III trials completed in Japan have suggested that the combination of irinotecan/cisplatin yields superior survival rates in stage IV NSCLC patients compared to vindesine/cisplatin. The principal toxicities of the irinotecan/cisplatin regimen are neutropenia and diarrhea. This regimen is currently being tested in Japan against regimens commonly used in the United States, such as cisplatin/gemcitabine, cisplatin/vinorelbine, and carboplatin/paclitaxel. These studies include evaluation of monthly as well as weekly schedules of cisplatin in combination with irinotecan as well as a triplet regimen of irinotecan/carboplatin/paclitaxel. Ongoing trials are evaluating these regimens as well as irinotecan/carboplatin and several nonplatinum-based irinotecan-containing doublets in both the first- and second-line treatment of advanced NSCLC. Several ongoing trials are attempting to integrate irinotecan with thoracic radiation therapy in stage III NSCLC. These trials are using irinotecan-containing regimens as induction and concurrent therapy with thoracic radiation therapy. Irinotecan is also being evaluated in the preoperative setting in early-stage resectable NSCLC. Many of these trials are also incorporating celecoxib, a potent inhibitor of the cyclooxygenase-2 pathway, in combination with irinotecan-containing regimens in both advanced as well as early-stage NSCLC. Future trials should focus on the integration of the new targeted agents in combination with irinotecan-containing regimens in all stages of NSCLC.
Clin Lung Cancer 2002 Nov
PMID:Irinotecan in non-small-cell lung cancer: status of ongoing trials. 1465 36

The prognosis for non-small-cell lung cancer (NSCLC) patients remains poor, with a high percentage of patients presenting with advanced disease and metastases. Thus, the therapeutic goal is to provide optimal local control and to eradicate any metastases. The advent of novel therapies has provided new hope in the treatment of this disease. Irinotecan, a topoisomerase I inhibitor, is active in both chemotherapy-naive and previously treated NSCLC patients. In addition, its ability to act as a radiosensitizer makes it a promising candidate for use in combined modality therapy. Encouraging response rates have been achieved in multiple trials using irinotecan alone or in combination with cisplatin, carboplatin, docetaxel, and/or radiotherapy. Further phase II and III studies should clarify the benefit of combined modality therapy as well as the optimal way to integrate radiotherapy into irinotecan regimens.
Clin Lung Cancer 2002 Nov
PMID:Irinotecan Combined with Radiation Therapy for Patients with Stage III Non-Small-Cell Lung Cancer: Current Trials. 1465 37

Irinotecan, a new topoisomerase I inhibitor, has significant activity in the treatment of untreated and previously treated patients with small-cell lung cancer (SCLC). In combination with cisplatin, a Japanese randomized trial showed a statistically significant survival advantage over cisplatin/etoposide in chemotherapy- naive patients with extensive-stage disease. This represents the first major advance in the treatment of extensive-stage SCLC in 20 years. Randomized trials in the United States are underway to confirm these impressive results. Meanwhile, trials incorporating irinotecan and cisplatin into treatment regimens for limited-stage disease are being conducted. Furthermore, irinotecan-containing regimens with other agents such as carboplatin, etoposide, and paclitaxel in first- or second-line therapies for SCLC are being evaluated. Preliminary results are encouraging. This article will highlight the exciting results achieved with irinotecan in SCLC and discuss its promising future in this disease.
Clin Lung Cancer 2001 May
PMID:Irinotecan in small-cell lung cancer: current data. 1472 23

Lung cancer is the leading cause of cancer death in the United States and in the world. In the United States, lung cancer ranks first in cancer deaths for both men and women. The 5-year survival rate is only 15%, but this has improved considerably from the 5% rate in the early 1960s. For many years, the standard therapy for patients with advanced, stage IIIB and IV non small-cell lung cancer (NSCLC) was best supportive care, which consisted of palliative radiotherapy, pain management, and other symptom management. The median survival for these patients was only 4 months, and more than 85% died in the first year after diagnosis. Cisplatin was the first drug that was shown to prolong the survival of patients with advanced lung cancer. Meta-analyses of randomized trials showed that cisplatin reduced the hazard rate of death by 26%, increased median survival from 4 to 6 months, and increased 1-year survival from 15% to 25%. Cisplatin-based therapy also relieved symptoms in the majority of patients and improved the quality of life as assessed by patients themselves. Still, further advances are desperately needed, as three fourths of the cisplatin-treated patients die within a year of diagnosis. Topoisomerase I inhibitors are a new class of chemotherapeutic agents introduced into lung cancer therapy during the 1990s. Irinotecan (CPT-11) was shown to be active in patients with both small-cell and non small-cell lung cancers. The activity of irinotecan in advanced NSCLC made it logical to combine irinotecan with the two platinums, cisplatin and carboplatin. The combination of irinotecan with cisplatin produced response rates of about 40% in phase II trials conducted in previously un-treated patients with advanced NSCLC. The median survival in these studies ranged from 6-8 months, and the 1-year survival rates ranged from 40%-60%. Because carboplatin is more convenient and better tolerated than cisplatin, a number of more recent phase II trials have evaluated the combination of irinotecan and carboplatin in patients with advanced NSCLC. These trials produced results similar to those achieved with irinotecan/cisplatin and with other two-drug combinations such as paclitaxel/carboplatin and gemcitabine/ cisplatin. The excellent activity of the two-drug combination or irinotecan and a platinum led to trials of three-drug combinations, such as irinotecan/carboplatin/paclitaxel. Preliminary results from these studies showed excellent survival, although the toxicity required some dosage reductions. Randomized trials will be necessary to determine whether such three-drug combinations will be preferred over standard two-drug combinations.
Clin Lung Cancer 2001 May
PMID:Irinotecan and platinums in the treatment of non small-cell lung cancer. 1472 25

Locally advanced non small-cell lung cancer (NSCLC) represents 30%-40% of all pulmonary malignancies. Despite the fact that the disease is confined to the chest, most patients will eventually succumb to their dis-ease. Therefore, the management of NSCLC is undergoing rapid evolution with hope of improving overall survival. The arrival of a new generation of chemotherapeutic agents, including the taxanes, gemcitabine, and topoisomerase inhibitors such as irinotecan and topotecan, offers the hope of real advances against this malignancy. Irinotecan and topotecan are camptothecin derivatives that are felt to exert their cytotoxic effects by targeting topoisomerase I. It is believed that topoisomerase I inhibitors stabilize a DNA-topoisomerase I cleavable complex, and interactions between this complex and the replication machinery may lead to cell death. There is a significant volume of in vitro and in vivo data demonstrating that these topoisomerase I inhibitors also act as radiosensitizers. Early clinical data with topotecan suggests that it is a more active agent in small-cell lung cancer than it is in NSCLC despite a common mechanism of action with irinotecan. With the increasing data that exist on the improved outcome with concurrent chemoradiation treatment for malignancies including lung cancer and head and neck cancers, there is an impetus to pursue the addition of other drugs that can radiosensitize tumors and further improve local control. Irinotecan is undergoing early clinical trials in the combined modality setting in several different disease sites. This paper will review the in vitro and in vivo data on the ability of irinotecan and topotecan to render tumors more susceptible to ionizing radiation. It will then focus on the experience with both drugs and thoracic radiation in the treatment of NSCLC, in which irinotecan has yielded acceptable toxicity results and response rates in excess of 60% in early trials. It is hoped that newer treatment strategies, such as the combination of radiation and topoisomerase I inhibitors in lung cancer, will have a significant impact on cure rates in the future.
Clin Lung Cancer 2001 May
PMID:Topoisomerase I inhibitors in the combined modality therapy of lung cancer. 1472 28

Irinotecan (CPT-11), a topoisomerase I inhibitor, has been shown in preclinical studies to be a potent radiosensitizer. Carboplatin, a known radiosensitizer with single-agent activity in non small-cell lung cancer (NSCLC), is felt to be a rational choice in combination with irinotecan. We have completed the initial portion of a phase I study, in patients with locally unresectable lung cancer, combining irinotecan with thoracic radiation. Thirteen patients have been entered onto this study through three dose levels (30 to 50 mg/m2/week) of irinotecan. There were seven partial responses in 12 evaluable patients, for an over-all response rate of 58%. Nausea, vomiting, and esophagitis were the principal toxicities of weekly irinotecan and concurrent thoracic radiation. As the maximum tolerated dose (MTD) of irinotecan with radiation has been established at 40 mg/m2/week, we are currently accruing patients to the second phase of this study with the addition of carboplatin (AUC = 2). Thus far toxicity has primarily been esophagitis.
Clin Lung Cancer 2000 May
PMID:A phase I trial of outpatient weekly irinotecan/carboplatin and concurrent radiation for stage III unresectable non small-cell lung cancer: a Vanderbilt-Ingram Cancer Center Affiliate Network Trial. 1473 37

Irinotecan is an active cytotoxic agent for various cancers, and is converted to SN-38, its most active metabolite, by carboxylesterase converting enzyme (CCE) in vivo. Although the primary metabolic site is in the liver, ex vivo studies have proven that irinotecan is also converted to SN-38 in intestines, plasma and tumor tissues. The present study attempted to elucidate the in vitro conversion efficiency in human plasma, and to examine possible inter-individual variability and its clinical significance. Plasma samples were taken from 57 patients with lung cancer, 3 patients with benign pulmonary diseases and 9 healthy volunteers. After addition of 157 mM irinotecan to plasma, time courses of SN-38 concentration, measured by high-performance liquid chromatography (HPLC), were investigated. All subjects showed linear increase in SN-38 concentration during the first 60-min period, followed by a plateau. Mean and standard deviation of the conversion rate in the first 60 min were 515.9 +/- 50.1 pmol/ml/h (n = 69), with a coefficient of variation of 0.097. Although most of the subjects showed comparable conversion rates, 3 subjects had significantly higher conversion rates. In conclusion, the results of this study suggest that the enzyme activity of CCE in human plasma may show inter-individual variability.
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PMID:In vitro conversion of irinotecan to SN-38 in human plasma. 1518 36

Among patients with lung cancer, approximately 15% have small-cell lung cancer (SCLC). The clinical characteristics of SCLC tend to be more aggressive, but also more sensitive to chemotherapy and radiation therapy than those of non-SCLC. Irinotecan (Camptosar) is a derivative of camptothecin, an inhibitor of the nuclear enzyme topoisomerase I. Irinotecan has been shown to exhibit excellent antitumor activity against SCLC in monotherapy regimens and in combination with cisplatin. A phase III trial comparing irinotecan and cisplatin (IP) with etoposide and cisplatin (EP) in patients with previously untreated extensive-stage SCLC (ED-SCLC) was conducted. Patients in the IP arm responded significantly better than patients in the EP arm. In the IP arm, the response rate was 84%, and median overall survival was 12.8 months. A phase II trial of irinotecan, cisplatin, and etoposide (IPE) administered weekly (arm A) or every 4 weeks (arm B) for ED-SCLC (JCOG 9902-DI) was also performed. In arm B, the response rate was 77% and the median overall survival was 12.9 months. A randomized trial comparing IP with IPE administered every 3 weeks in patients with previously untreated ED-SCLC is presently being performed in Japan.
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PMID:Topoisomerase I inhibitors in small-cell lung cancer. The Japanese experience. 1525 63


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