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

This multicenter study enrolled 73 patients with locally advanced or metastatic non-small-cell lung cancer (NSCLC). The study design was based on the hypothesis that the non-overlapping toxicities of a 3-drug combination of irinotecan (Camptosar, CPT-11), carboplatin (Paraplatin), and paclitaxel (Taxol) would allow them to be dosed at recommended or standard doses, respectively. Of the 32 patients in phase I portion of the trial, six received irinotecan 40 mg/m2 plus carboplatin at an area-under-curve (AUC) of 6 and paclitaxel 225 mg/m2 on an every-3-week schedule (regimen A). Due to the unexpectedly severe toxicity associated with this regimen, the carboplatin and paclitaxel doses were reduced, while the irinotecan doses were escalated from 40 to 80 to 125 mg and reduced to 100 mg/m2 (regimen B). In the phase II portion of the trial, irinotecan was dosed at 100 mg/m2 because 3 of 8 patients who received the 125 mg/m2 dose in phase I experienced first-course grade 3/4 toxicities. However, the toxicity of regimen B proved unacceptably severe in phase II; 13 of the 40 patients (35%) experienced grade 3/4 neutropenia and 30% suffered febrile or septic neutropenia. The unconfirmed objective response rate in phase I was 64.5%; median time to progression and median survival were 7.1 months and 11.6 months, respectively, and 1-year survival was 46.9%. The unconfirmed objective response rate in phase II was 60.6%, including one complete response (CR) and 19 partial responses (PRs); one CR and 16 PRs were subsequently confirmed. The efficacy and toxicity of this triple combination strongly suggest significant pharmacokinetic and/or pharmacodynamic interactions, warranting continued clinical investigation.
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PMID:Phase I/II trial of irinotecan, carboplatin, and paclitaxel in advanced or metastatic NSCLC. 1098 Dec 88

This phase I/II nonrandomized, open-label study was designed to assess the safety and benefit of sequencing irinotecan (Camptosar, CPT-11) plus paclitaxel (Taxol) immediately after cisplatin (Platinol)/etoposide (VePesid, VP-16) or carboplatin (Paraplatin)/etoposide in patients with extensive small-cell lung cancer (SCLC). Ten patients were evaluable in phase I; all had previously been treated with cisplatin and etoposide, and five of the 10 had also previously received carboplatin and paclitaxel. All 10 patients were given a fixed dose of irinotecan (60 mg/m2) and escalating doses of paclitaxel weekly for 3 weeks. Three patients had grade 4 toxicities, one at the lowest dose level of paclitaxel (15 mg/m2). Two patients had grade 3 toxicities. The dose-limiting toxicity occurred at the 60 mg/m2 paclitaxel dose level, when the performance status of both patients in that group decreased to 60 (Karnofsky scale). Two patients had progressive disease after 1 month of treatment and did not receive cycle 2. Three of seven patients evaluable for response had complete remissions. A fourth patient had resolution of lymphangitic metastases and resolution of a partial small bowel obstruction but did not have measurable disease. The fifth patient had a partial remission. The ongoing phase II portion of the study is restricted to previously untreated patients who will receive at least one cycle of either cisplatin or carboplatin in combination with etoposide followed by irinotecan at 60 mg/m2 and paclitaxel at 50 mg/m2 dosed once weekly for 3 weeks.
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PMID:Phase I/II study of weekly irinotecan and paclitaxel in patients with SCLC. 1098 Dec 93

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

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

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

Docetaxel (Taxotere) has shown activity both as a single-agent and in combination with multiple other cytotoxic agents in the front-line therapy of advanced, metastatic non-small-cell lung cancer (NSCLC). A randomized, phase III trial demonstrated a survival advantage for docetaxel over best supportive care in the front-line setting, with docetaxel achieving a 2-year survival of 12% vs 0% for best supportive care. Combinations of docetaxel with the platinum agents have been the most extensively studied in the front-line setting and have produced notably high response rates and encouraging median survivals. When compared to the paclitaxel/cisplatinum combination in a large, phase III randomized trial, the combination of docetaxel and cisplatin resulted in similar response, median survival, and 1-year survival rates. Another randomized phase III trial compared docetaxel/platinum combinations to the US Food and Drug Administration (FDA)-approved vinorelbine (Navelbine)/cisplatin regimen. The docetaxel/cisplatin combination produced a superior overall survival, 2-year survival, and overall response rates compared to vinorelbine/cisplatin. The combination of docetaxel and carboplatin (Paraplatin) demonstrated similar survival and response, and was associated with quality-of-life benefits over the vinorelbine/cisplatin arm. Docetaxel has been successfully combined with gemcitabine in multiple trials with impressive response and survival rates, and an acceptable toxicity profile. A large phase IIb trial demonstrated therapeutic equivalence and lesser toxicities for the docetaxel/gemcitabine combination compared to the combination of docetaxel and cisplatin. The docetaxel/gemcitabine combination therefore represents a viable nonplatinum regimen for first-line treatment of NSCLC. Other combinations that have been tested include docetaxel with vinorelbine, and docetaxel with irinotecan (CPT-11, Camptosar). Docetaxel is active in NSCLC and should be investigated further in combination with novel molecularly targeted drugs such as tyrosine kinase inhibitors, andfarnesyl transferase inhibitors.
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PMID:Docetaxel for locally advanced or metastatic non-small-cell lung cancer. Current data and future directions as front-line therapy. 1210 98

Several chemotherapeutic regimens have emerged in the past 5 years with the capability to improve survival and quality of life of patients with advanced non-small cell lung cancer (NSCLC). Among these treatments, the regimen of gemcitabine (Gemzar) and carboplatin (Paraplatin) has gained increasing acceptance. The combination of these two drugs was initially hampered by unacceptable platelet toxicity. However, the use of a 21-day schedule with the administration of gemcitabine on days 1 and 15 or the use of a 28-day schedule with the omission of day-15 gemcitabine has clearly been well tolerated and active. Unlike taxane based regimens, there is no need for steroid premedication, and neurotoxicity and alopecia are absent. This regimen is well tolerated and easily administered on an outpatient basis. It therefore represents an excellent "platform regimen" for the addition of new agents, particularly those associated with minimal myelotoxicity. Three-drug regimens consisting of gemcitabine/carboplatin and a taxane have been evaluated both with concurrent and sequential administration of the drugs. Trials are under way or planned for the addition of novel agents such as C225, UCN-01, PKC-alpha antisense, bexarotene, COX-2 inhibitors and other agents.
Lung Cancer 2002 Nov
PMID:Past, present, and future of gemcitabine and carboplatin regimens in advanced non-small cell lung cancer. 1243 28

A novel schema of intrapatient dose escalation was applied to determine a population-based maximum tolerated dose (pMTD) for irinotecan (CPT-11, Camptosar) and carboplatin (Paraplatin) in a phase I trial. A total of 74 patients with advanced solid tumors were enrolled with the following characteristics: men/women, 46/28; median age, 61 years; 51 patients with and 23 patients without prior chemotherapy; performance status of 0-1 (93%) and 2 (7%). Patients were started at dose level 1 with irinotecan at 200 mg/m2, and carboplatin at an area under the concentration-time curve (AUC) of 5 mg/mL x min, administered every 21 days. Depending on degree of toxicity observed, the dose for each patient in each subsequent cycle was determined according to a predetermined schema of dose levels. Individual maximum tolerated dose (iMTD) was determined for each patient. The pMTD was defined as the highest dose level for which the incidence of dose-limiting toxicity occurred in less than 33% of the patient population. The most common dose-limiting toxicity included neutropenia (58%), thrombocytopenia (15%), diarrhea (8%), and nausea/emesis (7%). The iMTD ranged from dose level-3 (irinotecan at 100 mg/m2 and carboplatin at an AUC of 4) to dose level 5 (irinotecan at 350 mg/m2 and carboplatin at AUC 6). The pMTD was determined to be dose level-1 and 1 for previously chemotherapy-treated and--untreated patients, respectively. Fifty-nine patients were assessable for response. Of note, a response rate of 40% was observed in 15 patients with relapsed small-cell lung cancer previously treated with platinum-based therapy. We recommend dose level 1 of irinotecan (200 mg/m2) and carboplatin (AUC 5) for chemotherapynaive patients, and dose level-1 of irinotecan (150 mg/m2) and carboplatin (AUC 5) for chemotherapy-treated patients in phase II trials.
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PMID:Population-based maximum tolerated dose of irinotecan and carboplatin. 1288 68

Recent findings indicate significant prolongation of survival and time to disease progression with irinotecan (CPT-11, Camptosar)/cisplatin vs etoposide/cisplatin in extensive-stage small-cell lung cancer, and a larger-scale phase III trial has been planned to provide more definitive data on the benefits of the irinotecan/cisplatin combination in this setting. Early-phase studies indicate that the activity of carboplatin (Paraplatin) in small-cell lung cancer is comparable to that of cisplatin, and that combining irinotecan on a day 1 and 8 schedule with split-dose carboplatin is feasible. Inhibition of the cyclooxygenase-2 (COX-2) enzyme, which is active in tumorigenesis, may augment efficacy and reduce toxicity of platinum/irinotecan combinations. A phase II trial has been designed to compare irinotecan/carboplatin and irinotecan/cisplatin combinations with or without the COX-2 inhibitor celecoxib (Celebrex) in patients with extensive-stage small-cell lung cancer. Results of these trials will help define the roles of platinum/irinotecan combinations and COX-2 inhibition in treatment for small-cell lung cancer.
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PMID:Irinotecan, cisplatin/carboplatin, and COX-2 inhibition in small-cell lung cancer. 1288 70

The outcome of patients with metastatic lung cancer is poor, with a 1-year survival rate of approximately 35%. We are evaluating the combination of irinotecan (CPT-11, Camptosar) and carboplatin (Paraplatin) in patients with stage IIIB and IV non-small-cell lung cancer. Eligible patients include those with histologic or cytologic diagnosis of non-small-cell lung cancer; no previous chemotherapy for metastatic lung cancer; and Eastern Cooperative Oncology Group performance status 0 or 1. The first five patients received irinotecan at 250 mg/m2 over 90 minutes followed by carboplatin at an area under the concentration-time curve (AUC) of 5 over 1 hour. Subsequently, the dose of irinotecan was 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 37 patients, 14 have been enrolled and 9 are evaluable for toxicity and response at the time of this report. Thirty-two cycles have been administered, with seven 1-week delays and two dose reductions. To date there have been two partial responses and five patients with stable disease; two patients developed progressive disease on therapy. One patient had neutropenic fever; other toxicities included mild pancreatitis (n = 1) and diverticulitis (n = 1). The regimen of irinotecan and carboplatin administered once every 3 weeks demonstrates early evidence of activity, and is tolerable and convenient. 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 non-small-cell lung cancer. 1288 71


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