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

Preclinical data suggest that irinotecan (Camptosar, CPT-11), a novel topoisomerase I inhibitor, has exhibited promising activity in the treatment of lung cancer. In a phase II study of non-small-cell lung cancer, irinotecan demonstrated a 32% response rate. Combinations of irinotecan and cisplatin (Platinol) have also demonstrated synergistic activity against non-small-cell lung cancer. A phase I trial of irinotecan combined with cisplatin in previously untreated non-small-cell lung cancer patients showed an encouraging response rate of 54%, with irinotecan at 60 mg/m2 on days 1, 8, and 15, plus cisplatin at 80 mg/m2. In a phase II study of chemotherapy-naive patients with stage IIIB/IV non-small-cell lung cancer, irinotecan/cisplatin yielded a response rate of 52% and a mean survival time of 44 weeks. Data from a phase III trial comparing cisplatin at 80 mg/m2 on day 1 plus vindesine at 3 mg/m2 on days 1, 8, and 15 with two irinotecan-containing regimens--cisplatin at 80 mg/m2 on day 1 plus irinotecan at 60 mg/m2 on days 1, 8, and 15, and single-agent irinotecan at 100 mg/m2 on days 1, 8, and 15--have also been reported. Responses were observed in 32%, 44%, and 21% of patients for the vindesine/cisplatin, irinotecan/cisplatin, and irinotecan arms, respectively, with corresponding median survival times of 45.6, 50.0, and 46.0 weeks; there were no significant differences in response rate or survival between treatment groups for all patients. However, subset analysis of stage IV patients indicated a significant survival advantage for irinotecan/cisplatin; the median survival time was 50 weeks for patients receiving irinotecan/cisplatin, 36.4 weeks for vindesine/cisplatin, and 42.1 weeks for irinotecan (P = .004 for the irinotecan/cisplatin arm vs vindesine/cisplatin; P = .018 for irinotecan vs vindesine/cisplatin). Another phase III study compared irinotecan/cisplatin and vindesine/cisplatin. There was no difference in overall median survival time, and the median survival times were not significantly different for stage IV patients in the respective irinotecan/cisplatin and vindesine/cisplatin arms (44.7 vs 45.3 weeks). Further studies are needed to determine whether irinotecan/cisplatin combinations improve survival in comparison with other promising platinum-containing regimens.
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PMID:Establishment of the standard regimen for non-small-cell lung cancer in Japan. 1122 Oct 16

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

Cisplatin (Platinol)-based chemotherapy has been the standard systemic therapy for both non-small-cell and small-cell lung cancer for the past 2 decades, though the efficacy and benefit remain modest. Recently, several novel agents have been introduced that have single-agent activity comparable to cisplatin and offer the possibility of improved therapy for lung cancer. Camptothecin and taxane derivatives are associated with both different mechanisms of action and nonhematologic toxicities, and have demonstrated additive or synergistic activity when used in combination in preclinical studies. We review pertinent clinical studies of these agents in lung cancer and present our experience in combining irinotecan (Camptosar, CPT-11) with taxanes on a weekly schedule in dose-finding and efficacy studies. When chemotherapy is delivered for 4 consecutive weeks followed by a 2-week rest, hematologic toxicity is dose limiting and most prominent during weeks 3 and 4. Dose intensification is feasible if the schedule is modified so the chemotherapy is given on days 1 and 8, with cycles repeated every 3 weeks. The most common nonhematologic toxicities remain asthenia, neuropathy, and diarrhea. Future studies will explore and better define the role of these drug combinations in the treatment of lung cancer.
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PMID:Rationale and dose-finding studies of the combination of irinotecan and a taxane on a weekly schedule. 1122 Oct 18

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

Survival in lung cancer patients has not improved over the past 2 decades. Irinotecan (Camptosar, CPT-11), a semisynthetic analog of the quinoline-based alkaloid camptothecin, is one of several new drugs that have demonstrated promising activity in the treatment of lung cancer in recent years. This article gives a brief overview of the mechanism, development history, and current uses of this agent.
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PMID:Current status of irinotecan in lung cancer. 1122 Oct 22

Chemotherapy is currently the main treatment for all stages of small-cell lung cancer. In extensive disease, etoposide/cisplatin (Platinol) is standard treatment, and in limited disease, etoposide/cisplatin with early concurrent thoracic radiotherapy twice daily is a typical regimen. Therapeutic outcomes, however, leave substantial room for improvement. The topoisomerase I inhibitor irinotecan (Camptosar, CPT-11) is one of the most active agents against small-cell lung cancer. In a phase II study, irinotecan yielded response rates of 33% to 50%, depending on prior treatment status. Combinations with cisplatin have resulted in a median survival of 14.3 months in patients with limited disease and 13.0 months in extensive disease. A phase III study in extensive-disease small-cell lung cancer compared irinotecan/cisplatin and standard etoposide/cisplatin regimens, and demonstrated a significant difference in survival in the irinotecan-containing arm (411 vs 282 days). Planned phase III studies in North America will confirm and extend these results. Based on these promising data, irinotecan/cisplatin regimens represent a new standard treatment for extensive-disease small-cell lung cancer.
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PMID:New state of the art in small-cell lung cancer. 1122 Oct 23

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

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

Irinotecan (CPT-11, Camptosar) is a camptothecin derivative that is thought to exert its cytotoxic effects by targeting topoisomerase I. It is believed that irinotecan stabilizes a DNA-topoisomerase I cleavable complex, and that 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 irinotecan acts as a radiosensitizer. The exact mechanism of this radiosensitization is currently unknown. The increasing amount of data demonstrating improved outcomes with concurrent chemoradiation treatment of malignancies like lung cancer and head and neck cancer provide impetus for pursuing the addition of other drugs as radiosensitizers to improve local control further. Irinotecan is undergoing early clinical trials in the combined-modality setting in several disease sites. This article will provide an overview of the current status of irinotecan used concurrently with radiotherapy in the treatment of a variety of solid tumors.
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PMID:Irinotecan and radiation in combined-modality therapy for solid tumors. 1149 28

Irinotecan (CPT-11, Camptosar), either alone or in combination with cisplatin (Platinol), has demonstrated activity in advanced non-small-cell lung cancer (NSCLC). In single-agent studies, response rates as high as 35% have been observed; in combination with cisplatin, response rates have ranged as high as 50%, with 1-year survival rates of 33% to 58%. A critical phase III randomized trial comparing irinotecan, either alone or in combination with cisplatin, to vindesine/cisplatin, demonstrated superior survival for stage IV patients receiving irinotecan. The first North American effort to replicate the schedule used in the phase III trial (cisplatin 80 mg/m2 and irinotecan 60 mg/m2 on days 1, 8, and 15 every month) yielded a response rate of 29%, median survival time of nearly 10 months, and 1-year survival rate of 37%. A subsequent multi-institutional trial conducted through Vanderbilt Cancer Center Affiliate Network and Fox Chase Cancer Center combined both agents on a weekly schedule in an attempt to exploit their putative synergy and to potentially decrease toxicity. This schedule, which employed irinotecan 65 mg/m2 and cisplatin 30 mg/m2 both weekly x 4, was better tolerated than the monthly cisplatin combination with a higher response rate (36%), median survival (11.6 months), and 1-year survival rate (46%). Multiple phase I and phase II studies have combined irinotecan with taxanes, either alone or in concert with carboplatin (Paraplatin), yielding similar response and survival rates. Finally, a critical phase III trial from Japan has demonstrated superior outcome for irinotecan and cisplatin vs standard etoposide/cisplatin in the treatment of extensive small-cell carcinoma of the lung. At least one North American trial will determine if these results are reproducible.
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PMID:The emerging world role of irinotecan in lung cancer. 1149 27


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