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

The search for new combination chemotherapeutic regimens for the treatment of non-small-cell lung cancer is motivated not only by the desire to increase the objective tumor response and survival rates, but also by the desire to reduce toxicity, decrease symptoms, and improve the psychological well-being of treated patients. At present, the overall phase II response rates with existing combination chemotherapeutic regimens are approximately 15% to 30%, and the median survival rates are about 8 to 9 months. The median 1-year survival rates are about 30% to 40%, while the 2-year survival rates are only about 10% to 15%. Thus, while we have made substantial progress in the treatment of this disease, the long-term outcome is still relatively bleak. This article reviews the results of a phase I trial with a new combination chemotherapeutic regimen (gemcitabine [Gemzar] and the novel antifolate, Alimta), and outlines the rationale for, and design of, an ongoing phase II trial.
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PMID:Gemcitabine/Alimta in locally advanced or metastatic non-small-cell lung cancer. 1096 Sep 46

Over the last decade, a group of new agents with differing mechanisms of action have shown great promise in early clinical studies in non-small-cell lung cancer (NSCLC). These include the taxanes docetaxel (Taxotere) and paclitaxel (Taxol); the nucleoside analog gemcitabine (Gemzar); the vinca alkaloid vinorelbine (Navelbine); the topoisomerase-I inhibitor irinotecan (Camptosar, CPT-11); and the bioreductive agent tirapazamine. Cisplatin (Platinol), which has been the "backbone" of combination chemotherapy in patients with NSCLC because of its proven single-agent activity, has been examined in combination with these agents as well as radiation and surgery in numerous trials. This article summarizes trials of these combination therapies in the treatment of NSCLC.
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PMID:Chemotherapy in metastatic non-small-cell lung cancer. 1098 Dec 87

There will be approximately 40,000 new cases of small-cell lung cancer this year. Prior to 1990, there were several agents with single-agent response rates of 30% to nearly 90% in the untreated small-cell lung cancer population and approximately 10% to 20% in relapsed patients. During the 1990s, several new chemotherapy agents have displayed activity in small-cell lung cancer (paclitaxel [Taxol], gemcitabine [Gemzar], vinorelbine [Navelbine], topotecan [Hycamtin], and irinotecan [Camptosar, CPT-11]). The majority of studies with irinotecan have been conducted in Japan. The US experience is limited to a single multi-institution trial that was conducted in patients with previously treated small-cell lung cancer. A total of 44 patients were entered in the study. Patients were stratified by response to prior therapy. Responses occurred in 7 of 44 patients for an overall response rate of 14%. The overall median survival was 4.8 months.
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PMID:Irinotecan in small-cell lung cancer: the US experience. 1122 Oct 15

Topoisomerase I inhibitors have demonstrated significant activity in non-small-cell lung cancer. In phase II studies, particularly in Japan, single-agent irinotecan (Camptosar, CPT-11) has produced response rates as high as 35%. In combinations with cisplatin (Platinol), it has also resulted in overall response rates of 41% to 52%, with median survival of 10.2 to 13 months, and 1-year survival rates of 33% and 58%. A Japanese phase III randomized trial of irinotecan, either alone or in combination with cisplatin vs vindesine/cisplatin in previously untreated stage IIIB/IV non-small-cell lung cancer, demonstrated that survival among stage IV patients was significantly better in the irinotecan arms compared to the vindesine/cisplatin group. However, another Japanese phase III study comparing irinotecan/cisplatin to vindesine/cisplatin failed to show a survival difference. Initial North American efforts recapitulated this work, while a follow-up study incorporated weekly irinotecan with weekly cisplatin, yielding a response rate of 36%, median survival of 11.6 months, and a 1-year survival rate of 46%. Irinotecan/taxane combinations have also shown promise. Phase I/II studies in advanced non-small-cell lung cancer with paclitaxel (Taxol), irinotecan, and carboplatin (Paraplatin) produced a response rate of 38%, median survival of 11 months, and a 1-year survival rate of 47%; other trials with irinotecan and paclitaxel are ongoing. Phase I data for irinotecan/docetaxel (Taxotere) have indicated an overall response rate of 32%, median survival of 39 weeks, and a 1-year survival rate of 38%; subsequent phase II trials used either cisplatin or irinotecan in combination with docetaxel and yielded a promising median survival of 45.6 weeks, comparable to the standard cisplatin/docetaxel combination. Phase I trials with irinotecan and gemcitabine (Gemzar) have also yielded promising results. Follow-up efforts include phase II studies in both chemonaive advanced non-small-cell lung cancer and progressive small-cell lung cancer (salvage therapy). Clearly, clinical trial data have demonstrated the utility of irinotecan in the treatment of advanced non-small-cell lung cancer. Planned combinations with new chemotherapeutic agents and biological response modifiers may provide additional treatment options.
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PMID:Treatment of non-small-cell lung cancer in North America: the emerging role of irinotecan. 1122 Oct 17

The management of non-small-cell lung cancer is undergoing rapid evolution. Although the advent of combined-modality therapy has led to improved survival, most patients eventually succumb to the disease. The arrival of a new generation of chemotherapeutic agents--including the taxanes, gemcitabine (Gemzar), and topoisomerase inhibitors such as irinotecan (Camptosar, CPT-11)--offers the hope of advances against this malignancy. Irinotecan, a camptothecin derivative, has shown impressive activity in a variety of solid tumors, including non-small-cell lung cancer. It is believed to act by stabilizing the topoisomerase-DNA complex formed during diverse cellular processes, including replication and transcription. A considerable body of evidence also demonstrates that camptothecin and its derivatives possess substantial radiosensitization properties. This article will review the in vitro and in vivo data on irinotecan's ability to render tumors more susceptible to ionizing radiation. It will then focus on experience with irinotecan and thoracic radiation in the treatment of non-small-cell lung cancer, which 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 irinotecan in lung cancer--will significantly impact cure rates in the future.
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PMID:Irinotecan in combined-modality therapy for locally advanced non-small-cell lung cancer. 1122 Oct 19

Gemcitabine (Gemzar) and irinotecan (CPT-11, Camptosar) are active cytotoxic drugs against pancreatic cancer. Preclinical data evaluating the combination of gemcitabine and irinotecan suggest dose-dependent synergistic interactions in SCOG small-cell lung cancer and MCF-7 breast cancer cell lines. Two phase I trials of this combination have been reported to date: the day 1 and 8 every-3-week schedule (IrinoGem trial), and the day 1, 8, and 15 every-4-week schedule (MSKCC trial). Both trials aimed to determine the maximum tolerated dose of irinotecan when administered as a 90-minute i.v. infusion either immediately after (IrinoGem) or before or immediately after (MSKCC) gemcitabine at 1,000 mg/m2 by 30-minute i.v. infusion in patients with solid tumors. The achieved maximum tolerated dose of IrinoGem has a higher dose intensity of irinotecan (100 mg/m2 on days 1 and 8, every-3-week cycle) compared with the MSKCC schedule (60 mg/m2 on days 1, 8, and 15, every-4-week trial). In IrinoGem, two of three previously untreated metastatic pancreas cancer patients had durable radiologic partial responses. The third had stable disease with clinical benefit for eight cycles. In addition, a patient with metastatic adenocarcinoma of unknown primary--potentially pancreatic--has had a durable response and is alive more than 30 months after the diagnosis. Preliminary results of a 45-patient multicenter phase II trial with IrinoGem in advanced and metastatic pancreas cancer were recently reported. Toxicity was modest, with no toxic deaths or neutropenic fever. Radiologic response rate was 20% of patients (9 out of 45), and a CA 19-9 decrease of more than 50% from baseline values occurred in 32.5% of patients (13 out of 40). Median survival was 6 months (range: 0.9 to 12.2+ months) and median time to treatment failure was 2.9 months (range: 0.1 to 11.3+ months). A pivotal international multicenter phase III trial comparing IrinoGem to single-agent gemcitabine in advanced and metastatic pancreas cancer is ongoing.
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PMID:Irinotecan/gemcitabine combination chemotherapy in pancreatic cancer. 1130 41

Combinations of gemcitabine (Gemzar) with cisplatin (Platinol) are among the most active new chemotherapy regimens developed for advanced non-small-cell lung cancer. Carboplatin (Paraplatin) is a platinum analog devoid of many of the nonhematologic toxicities associated with cisplatin. Although few direct comparisons have been made, when administered by area under the concentration-time curve (AUC) dosing, carboplatin is probably equivalent to cisplatin in advanced non-small-cell lung cancer and provides an improved therapeutic index. Based on its favorable toxicity profile, carboplatin has supplanted cisplatin for use in combination with paclitaxel in several different tumor types. Initial trials combining gemcitabine and carboplatin using standard days 1, 8, and 15 dosing of gemcitabine suggested that thrombocytopenia was problematic. More recently, 21-day schedules in which gemcitabine is administered only on days 1 and 8 have demonstrated both efficacy and improved toxicity profiles. Here we review recent studies investigating gemcitabine plus carboplatin and preliminary data regarding combinations of gemcitabine with the new platinum analog oxaliplatin.
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PMID:Gemcitabine in combination with new platinum compounds: an update. 1130 43

Gemcitabine (Gemzar), paclitaxel (Taxol), docetaxel (Taxotere), and vinorelbine (Navelbine) are among the most active agents for the treatment of non-small-cell lung cancer and are generally more active than platinum compounds. When combined with a platinum compound, these agents have produced the best survival outcomes seen to date in non-small-cell lung cancer. More than 100 clinical trials have defined and expanded the role of gemcitabine, which has been combined with each of these agents to create novel combinations. Several new nonplatinum-based combinations compare favorably with platinum-based combinations with respect to toxicity and efficacy. Moreover, changing the schedule of gemcitabine administration from days 1, 8, 15 every 4 weeks to days 1 and 8 every 3 weeks seems to allow greater dose intensity with less severe toxicity and slightly greater efficacy. Coadministration of docetaxel, paclitaxel, or vinorelbine with gemcitabine on days 1 and 8 every 3 weeks is a promising approach. In addition to a lower incidence of severe neutropenia, docetaxel, paclitaxel, and vinorelbine protect against gemcitabine-associated thrombocytopenia.
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PMID:Gemcitabine and nonplatinum combinations in non-small-cell lung cancer. 1130 44

Current agents for the treatment of non-small-cell lung cancer include gemcitabine (Gemzar), paclitaxel (Taxol), docetaxel (Taxotere), vinorelbine (Navelbine), and irinotecan (CPT-11, Camptosar). Experimental agents include pemetrexed (LY231514, Alimta) and tirapazamine. Molecular and biological therapies include angiogenesis inhibitors, epidermal growth factor receptor inhibitors, HER2/neu inhibitors, and inhibitors of ras activation and function. Doublet chemotherapy is currently the standard treatment for advanced non-small-cell lung cancer. In the past 2 years, randomized trials have shown that many of the new two-drug combinations used to treat non-small-cell lung cancer have equivalent efficacy. These combinations produce 1-year survival rates of about 35% and 2-year survival rates of about 15%. Toxicity rates vary but are sufficiently low as to make the development of three-drug combinations feasible. Preliminary studies from several phase I and II trials suggest that triplet therapy can improve survival beyond that of double therapy regimens.
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PMID:Triplet combination chemotherapy and targeted therapy regimens. 1130 45

Platinum-based chemotherapy regimens have been the mainstay of treatment for non-small-cell lung cancer because they improve survival. Although there is no standard platinum-based regimen, combination regimens with newer agents (e.g., gemcitabine [Gemzar], paclitaxel [Taxol], and vinorelbine [Navelbine]) are superior to platinum alone or in combination with older agents (e.g., etoposide). Four phase III clinical studies demonstrate the favorable activity and toxicity profile of gemcitabine in combination with cisplatin (Platinol) for the treatment of patients with stage IIIB or IV non-small-cell lung cancer. These studies show overall response rates of approximately 30% to 60% with gemcitabine regimens versus overall response rates of 11% with cisplatin alone, 22% with cisplatin plus etoposide, 25% with cisplatin plus vinorelbine, and 40% with cisplatin plus mitomycin and ifosfamide (Ifex). Median survival time with gemcitabine regimens ranged from 8.1 to 9.8 months. Thrombocytopenia and anemia are the principal toxicities with gemcitabine regimens. Because of the favorable results with gemcitabine regimens, this drug is being evaluated in combination with carboplatin (Paraplatin) in newly diagnosed patients with stage IIIB or IV disease and good performance status, or as single-agent therapy in patients with poor performance status.
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PMID:Gemcitabine for the treatment of non-small-cell lung cancer. 1130 46


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