Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0684249 (lung carcinoma)
 23,830 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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

Small-cell lung cancer (SCLC) is a particularly aggressive form of lung cancer and is associated with a poor prognosis, rapid tumor growth, and early metastasis. Currently, the cornerstone of treatment in SCLC consists of combination therapy, with platinum/etoposide being the regimen of choice. Unfortunately, even with these advances in treatment, the median survival for patients with limited-stage disease is 10-15 months and 7-11 months for patients with extensive-stage disease. New treatment mechanisms need to be explored in order to extend the survival of SCLC patients. One such new treatment is the topoisomerase I inhibitor, irinotecan. This drug represents a promising advancement in the treatment of SCLC.
Clin Lung Cancer 2002 Nov
PMID:Irinotecan in small-cell lung cancer: current data and the status of ongoing trials. 1465 39

The value of platinum compounds has come into question with the advent of newer chemotherapy agents in the management of patients with advanced non-small-cell lung cancer. These newer agents, which include the taxanes, topoisomerase I inhibitors, gemcitabine, and vinorelbine, appear to have higher single-agent response rates and more favorable toxicity profiles when compared to the platinum compounds. However, the toxicity of the platinum compounds is now minimized with the advent of more effective antiemetics. In addition, phase III clinical trials have demonstrated that the strategy of cisplatin dose intensity and prolonged duration of therapy with platinum compounds does not improve overall survival; therefore, moderate doses of cisplatin and a shorter duration of therapy can be given to further decrease toxicity. Furthermore, while phase II trials utilizing nonplatinum-based combination chemotherapy appear to demonstrate superior response rates and survival in comparison to platinum-based doublets, results of phase III trials have demonstrated no improvement in survival. Platinum combination chemotherapy remains the standard approach for stage IV non-small-cell lung cancer. More substantial advances will likely be made with novel molecular targeted therapy, such as the epidermal growth factor receptor inhibitors, which demonstrate synergy with the platinum compounds.
Clin Lung Cancer 2002 May
PMID:The value of platinum compounds in non-small-cell lung cancer. 1466 32

Small-cell lung cancer (SCLC) accounts for 20%-25% of all new cases of lung cancer and represents the sixth most commonly diagnosed cancer in the United States. Given the tumor's systemic nature and chemoresponsiveness, chemotherapy has become the cornerstone of its management. Chemotherapy significantly prolongs survival; however, most of the patients still die within 2 years of diagnosis. Combination chemotherapy represents the treatment of choice for this disease. In the United States, cisplatin/etoposide is the regimen most frequently used for the first-line therapy of SCLC patients because of its better therapeutic index. Upon recurrence, topotecan is the Food and Drug Administration-approved treatment based on a phase III trial that showed no statistically significant differences in survival or response for topotecan compared with CAV (cyclophosphamide/doxorubicin/vincristine) but a better disease-related symptom improvement compared to baseline favoring the topoisomerase I inhibitor. Newer agents, with novel mechanisms of action, have shown activity against SCLC and are being tested in many different combinations. Among these agents, gemcitabine has attractive mechanisms of action and toxicity profile. Gemcitabine is a pyrimidine nucleoside antimetabolite, analogue to cytosine arabinoside, which through incorporation into the DNA leads to inhibition of DNA synthesis and cytotoxicity. As a single agent, gemcitabine has modest activity against SCLC. However, like with many other drugs, response rates improve when gemcitabine is used in combination regimens. Phase II and III studies of combinations with classic drugs for the management of SCLC patients such as cisplatin and/or etoposide and gemcitabine demonstrate comparable results to those of standard therapies. The gemcitabine/paclitaxel and gemcitabine/topoisomerase I inhibitor combinations are also of great interest, and preliminary results in previously treated patients are promising. The proper role of gemcitabine in the treatment of patients with SCLC awaits future testing in randomized phase III trials.
Clin Lung Cancer 2003 Jan
PMID:New agents in the treatment of small-cell lung cancer: focus on gemcitabine. 1472 Mar 38

Lung cancer continues to be the leading cause of cancer-related death in the United States. Small-cell lung cancer constitutes 15%-20% of all cases of lung cancer. It is a chemosensitive disease with an overall response rate of 70%-90% in first-line treatment. However, the majority of patients relapse, and further treatment at that time is unlikely to achieve a durable response. Among the new drugs studied in this disease, topoisomerase I inhibitors are emerging as active agents with significant activity in both untreated and relapsed disease. This paper reviews the current status of irinotecan and topotecan in the treatment of small-cell lung cancer.
Clin Lung Cancer 2001 May
PMID:Role of topoisomerase I inhibitors in small-cell lung cancer. 1472 Mar 60

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

Small-cell lung cancer (SCLC) accounts for approximately 20%-25% of all cases of lung cancer and has an especially poor prognosis, resulting in about 25% of all lung cancer deaths. About two thirds of patients with SCLC will present with more advanced and less treatment-sensitive extensive disease (ED). Five-year survival is negligible for patients with ED. Combination chemotherapy is the most effective treatment modality for SCLC. For patients with ED SCLC, chemotherapy can increase median survival from about 1.5 months to 7-11 months, with 2-year survival uncommon. Several new agents, including carboplatin, ifosfamide, and the taxanes, have been shown to be active against SCLC but have not resulted in improvement in overall survival. Among the most active to date has been the topoisomerase I inhibitor, irinotecan. A recent phase III study of the combination of irinotecan/cisplatin indicates improved survival over cisplatin/ etoposide. Survival results indicate that overall survival with irinotecan/cisplatin was significantly better than the standard treatment arm (12.8 months vs. 9.4 months, P = 0.0021, unadjusted one-sided log-rank test). These results represent a major advance and, if confirmed, may establish this regimen as the new standard of care for ED SCLC. These future directions will include the confirmation of the Japanese phase III trial in ED SCLC, evaluating the role of irinotecan in limited-stage disease, new doublet and triplet combinations containing irinotecan, and evaluation of irinotecan combinations with the newer molecularly targeted agents (ie, SU5416).
Clin Lung Cancer 2001 May
PMID:Irinotecan: future directions in small-cell lung cancer. 1472 24

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

Luotonin A is a cytotoxic alkaloid that has been shown to inhibit topoisomerase I via stabilization of the binary complex topoisomerase-DNA in the same fashion as camptothecin. The synthesis and the cytotoxic activity on the lung carcinoma cell line H460 of a series of derivatives of Luotonin A is reported. The compounds inhibit topoisomerase I but show weak cytotoxic activity, thus confirming the peculiarity of ring E of camptothecin for antitumor activity.
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PMID:Synthesis and cytotoxic activity of substituted luotonin A derivatives. 1550 Oct 36


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