[Pillnitz interdisciplinary discussion--summary].
Explore the source record for details and available documents.
Carcinoma, Non-Small-Cell Lung↗
Biomedical subjects
Ulrich Gatzemeier
Publications and source records attributed to Ulrich Gatzemeier.
Efficient palliation in patients with small-cell lung cancer by a combination of paclitaxel, etoposide and carboplatin: quality of life and 6-years'-follow-up results from a randomised phase III trial.
PURPOSE: Based on the promising activity of paclitaxel in small-cell lung cancer (SCLC) we conducted a randomized phase III trial to evaluate whether a combination of paclitaxel, carboplatin and etoposide phosphate (TEC) improves survival and time to progression as well as tolerability and quality of life (QoL) compared to a regimen of carboplatin, etoposide phosphate and vincristine (CEV) in SCLC patients. PATIENTS AND METHODS: Six hundred and fourteen patients with stages I-IV SCLC were randomly assigned between January 1998 and December 1999 to both treatment arms. All patients were evaluated for response rate, survival, side effects and quality of life with overall survival (OS) serving as primary endpoint. A final analysis was done after a six-year follow-up. Survival curves were estimated using Kaplan-Meier curves and tested with the log-rank test. Quality of life data were assessed in using the EORTC QLQ-C30 questionnaire and evaluated by calculating and comparing the mean scores as well as applying longitudinal techniques. RESULTS: Six hundred and eight patients were evaluable for efficacy and toxicity. The long-term follow-up confirms the significant survival benefit for the paclitaxel, etoposide, carboplatin (TEC) regimen with a median OS of 12.5 months compared to 11.7 months for the CEV arm (HR, 1.21; 95% CI, 1.02-1.43; P=.030). The 5-year survival rates were 14% for the experimental versus 6 % for the CEV arm. Significant survival prolongation was also observed in the subgroup of patients with stage IV disease (HR, 1.27; 95% CI, 1.00-1.60; P=.047). The previously reported clinical benefit in form of an overall reduction of grade 3/4 toxicity was backed by the results of the comprehensive QoL analysis we report hereby. TEC significantly improves the relevant QoL parameters like global overall QoL or physical functioning. CONCLUSION: When administered in combination with etoposide and carboplatin, paclitaxel is able to offer in SCLC patients with extensive disease a survival benefit without additional toxicities, but with gains in patient-reported quality of life. In terms of efficient palliative care, TEC might be seen as an alternative to standard cisplatin plus etoposide in patients requesting a powerful palliative regimen not compromising any survival benefit.
Adolescent↗
Gefitinib monotherapy in chemotherapy-naive patients with inoperable stage III/IV non-small-cell lung cancer.
BACKGROUND: Gefitinib is an orally active epidermal growth factor receptor tyrosine kinase inhibitor with activity in previously treated patients with advanced-stage non-small-cell lung cancer (NSCLC). However, little is known of its activity as monotherapy in chemotherapy-naive patients. This phase II study (1839IL/0456) evaluated first-line gefitinib in patients with advanced-stage NSCLC. PATIENTS AND METHODS: Eligible patients with proven inoperable stage III/IV NSCLC, no previous chemotherapy, and a performance status of 0-2 received gefitinib 250 mg per day until disease progression. Patient reevaluation was performed by radiography and computed tomography at regular intervals. RESULTS: Fifty-eight of 59 patients were available for analysis. Response rate (complete plus partial responses) was 5% (3 of 58 patients); 40% (23 of 58 patients) exhibited stable disease (overall disease control rate, 45% [26 of 58 patients]). Median progression-free survival was 7 weeks, and median overall survival was 29 weeks. All responders were women and/or nonsmokers with adenocarcinoma or bronchoalveolar carcinoma. Gefitinib treatment was well tolerated; skin toxicities occurred in 71% of patients, including severe skin toxicities in 2 patients, and mild to moderate diarrhea occurred in 50% of patients. CONCLUSION: Gefitinib monotherapy has some efficacy in chemotherapy-naive patients with advanced-stage or metastatic NSCLC. However, activity seems to be limited to particular patient groups.
Adult↗
[EGFR/HER1 inhibition: an example of new targeted therapies in non-small cell lung cancer].
BACKGROUND: Lung cancer is one of the most common forms of cancer in western industrialized countries. Patients with advanced non-small cell lung cancer (NSCLC) have a poor prognosis and suffer many tumor-associated symptoms. Unfortunately, approximately 70% of patients with NSCLC present themselves with advanced poor-prognosis stage III and IV disease. In advanced disease, treatment is palliative and symptom-oriented. New less Adenotoxic drugs are urgently needed. One of the targets of new agents is the human epidermal growth factor receptor (EGFR/HER1), and agents targeting this receptor include erlotinib, gefitinib and cetuximab. CLINICAL STUDIES: Erlotinib, gefitinib and cetuximab have been investigated in different clinical studies and provided objective responses and symptom relief. A benefit in survival could only be observed in second- and third-line therapy with erlotinib. All new agents have been generally well tolerated. Erlotinib was recently approved in the USA and Europe for second- and third-line treatment of patients with locally advanced or metastatic NSCLC. CONCLUSION: Anti-EGFR has shown promising antitumor activity in NSCLC with a mild toxicity profile. However, some clinical issues such as screening for potentially responsive patients and optimal combination with other drugs should be the aim of future studies.
Antibodies, Monoclonal↗
EGFR tyrosine kinase inhibitors in non-small cell lung cancer: report of a 3-year compassionate use experience with gefitinib in stage IIIB/IV outpatients.
BACKGROUND: Since March 2002, 240 patients with advanced stage IIIB/IV non-small cell lung cancer (NSCLC) have been treated inside a compassionate use program with oral gefitinib (250 mg o.d.). PATIENTS AND METHODS: Within a 36-month observation period, 32 patients who showed either partial remission or confirmed disease stabilization for at least 3 months, were retrospectively analyzed. RESULTS: Our reported 4% overall response rate matches with literature data for an unselected patient population. The median progression-free survival (PFS) was 9 months, the median overall survival (OS) since detection of advanced disease was 21 months. Interestingly, no relevant differences in PFS were observed for chemo-naive and second/third-line patients, whereas a reduced benefit in terms of response rate, PFS and OS was found for forth-line patients. 12 patients survived for at least 2 years since manifestation of their advanced disease. A slight benefit regarding cough and performance status conservation was observed. Mild to modest skin reactions and diarrhea were the adverse events reported most often. Grade 3 toxicities were rarely observed. CONCLUSIONS: The retrospective evaluation of therapy results from compassionate use patients helps clinicians to better evaluate new drugs in practice. EGFR tyrosine kinase (TK) inhibitors require ongoing intensive evaluation to optimize their clinical use in NSCLC.
Adult↗
Randomized phase III study of matrix metalloproteinase inhibitor BMS-275291 in combination with paclitaxel and carboplatin in advanced non-small-cell lung cancer: National Cancer Institute of Canada-Clinical Trials Group Study BR.18.
PURPOSE: To determine whether BMS-275291, a broad-spectrum matrix metalloproteinase inhibitor (MMPI), added to systemic chemotherapy improved survival in advanced non-small-cell lung cancer (NSCLC). In early phase studies, BMS- 275291 was not associated with dose-limiting joint toxicity seen with other MMPIs. PATIENTS AND METHODS: Chemotherapy-naive patients with stage IIIB/IV NSCLC, performance status (PS) 0 to 2, and adequate organ function were eligible. All patients received paclitaxel 200 mg/m2 plus carboplatin (area under the curve, 6 mg/mL-min) intravenously every 21 days for up to 8 cycles, and were randomly assigned to receive BMS-275291, 1,200 mg orally daily, or placebo until disease progression. The primary study end point was survival (OS); secondary end points included progression-free survival (PFS), response rates (RR), toxicity, and quality of life. RESULTS: From 2000 to 2002, 774 patients were randomly assigned. Pretreatment characteristics were well balanced between arms: median age, 61 years; male sex, 73%; stage IV, 79%; PS 0 to 1, 88%. Interim safety analysis revealed no survival advantage and increased toxicity in the experimental arm, and study treatment was stopped. Median OS, PFS and RR in the final analysis in the BMS-275291 arm were 8.6 months, 4.9 months, and 25.8% respectively, and in the control arm 9.2 months, 5.3 months, 33.7%. Toxicity was significantly higher in the BMS-275291 arm, including flu-like symptoms, rash, hypersensitivity reactions (8.6% v 2.4%), and febrile neutropenia (9.7% v 5.5%). CONCLUSION: BMS-275291 added to chemotherapy increases toxicity and does not improve survival in advanced NSCLC.
Administration, Oral↗
Phase III study of matrix metalloproteinase inhibitor prinomastat in non-small-cell lung cancer.
PURPOSE: Matrix metalloproteinases (MMPs) degrade extracellular proteins and facilitate tumor growth, invasion, metastasis, and angiogenesis. This trial was undertaken to determine the effect of prinomastat, an inhibitor of selected MMPs, on the survival of patients with advanced non-small-cell lung cancer (NSCLC), when given in combination with gemcitabine-cisplatin chemotherapy. PATIENTS AND METHODS: Chemotherapy-naive patients were randomly assigned to receive prinomastat 15 mg or placebo twice daily orally continuously, in combination with gemcitabine 1,250 mg/m2 days 1 and 8 plus cisplatin 75 mg/m2 day 1, every 21 days for up to six cycles. The planned sample size was 420 patients. RESULTS: Study results at an interim analysis and lack of efficacy in another phase III trial prompted early closure of this study. There were 362 patients randomized (181 on prinomastat and 181 on placebo). One hundred thirty-four patients had stage IIIB disease with T4 primary tumor, 193 had stage IV disease, and 34 had recurrent disease (one enrolled patient was ineligible with stage IIIA disease). Overall response rates for the two treatment arms were similar (27% for prinomastat v 26% for placebo; P = .81). There was no difference in overall survival or time to progression; for prinomastat versus placebo patients, the median overall survival times were 11.5 versus 10.8 months (P = .82), 1-year survival rates were 43% v 38% (P = .45), and progression-free survival times were 6.1 v 5.5 months (P = .11), respectively. The toxicities of prinomastat were arthralgia, stiffness, and joint swelling. Treatment interruption was required in 38% of prinomastat patients and 12% of placebo patients. CONCLUSION: Prinomastat does not improve the outcome of chemotherapy in advanced NSCLC.
Adult↗
Topotecan and etoposide as first-line therapy for extensive disease small cell lung cancer: a phase II trial of a platinum-free regimen.
In the treatment of extensive disease of small cell lung cancer (ED SCLC) there is an urgent need for more effective and better-tolerated drug regimens. We report on a prospective phase II trial performed to evaluate the efficacy and safety of a platinum-free regimen--containing topotecan and etoposide--in the first-line treatment of ED SCLC. Between December 1999 and July 2001, 28 chemotherapy-naive patients with ED SCLC were recruited; 9 patients had stage IIIB disease and 19 patients had stage IV disease. Based on phase I results, patients received treatment with intravenous topotecan 1 mg/m2 (days 1-5) followed by intravenous etoposide 75 mg/m2 (days 8-10). Treatment courses were repeated every 28 days for a maximum of 6 cycles. A confirmed response rate of 46.4% with 1 complete response (CR) and 12 partial responses (PR) (95% CI=27.5-66.1%) was observed. Stable disease (SD) was observed in 18% of patients. The median time to response was 7.9 weeks (range: 7.7-15.1 weeks) and median survival was 29.9 weeks (range from 3.3 to 91.4 weeks). Main toxicities encountered were haematological with Grade III/IV neutropenia in 2.6/1.5% of courses and Grade III/IV thrombocytopenia in 1.8%/0.7% of courses. These toxicities were manageable and were not associated with clinical sequels. Non-haematological toxicities were generally mild with no Grade III/IV toxicities reported apart from Grade III alopecia. The combination therapy of topotecan and etoposide is active in first-line chemotherapy for patients with ED SCLC. The regimen showed a tolerable safety profile. Since drug scheduling plays a critical role in the combination of topoisomerase I and II inhibitors, concurrent administration of topotecan and etoposide might increase the efficacy.
Adult↗
Benefit in lung function improvement and side-effect profile of long-term responders: an analysis of 14 NSCLC patients treated for at least 9 months with gefitinib.
BACKGROUND: Gefitinib is the first approved EGFR tyrosine-kinase inhibitor indicated for the treatment of patients with locally advanced (IIIB) or metastatic NSCLC after failure of platinum-based first-line therapy and docetaxel chemotherapy. Following rapid approval in Japan and accelerated approval based on phase-II results in the US, a large compassionate-use program has been set up in parallel to extended phase-III testing. Offering therefore access to state-of-the-art therapy to patients who are not candidates for clinical studies; Iressatrade mark EAP allows physicians to test the new EGFR inhibitor across a heterogeneous patient population characteristic for advanced NSCLC. PATIENT AND METHODS: After having treated 240 patients at the Grosshansdorf hospital, we have retrospectively analysed the efficacy and tolerability of 250 mg/day gefitinib in patients showing a long-term tumor control. We reviewed the patient records of 14 patients with advanced NSCLC that received daily gefitinib for at least 9 months. RESULTS: Long-term tumor control, defined as confirmed objective tumor response for at least 6 months or disease stabilisation for above 9 months, was observed in chemo-naive patients as well as in fourth-line therapy patients for the latter ones independently of the composition of prior chemotherapy. Most patients (9/14) with such a lasting benefit were female; patients' histology was in most cases uniform: adenocarcinomas were dominant in women and bronchioloalveolar carcinoma in men. Patients with moderate to severe dyspnoea benefited from a measurable improvement of their respiratory capacity. No cumulative toxicity was observed; characteristic side-effects for gefitinib as grades 1-2 diarrhoea or mild to moderate skin toxicity were well manageable. CONCLUSION: For 14 (6%) out of 240 patients with patterns of diffuse disseminated metastatic disease, gefitinib offered a lasting tumor control with a disease progression-free survival interval between 9 and 25 months. In parallel to therapy, patients' performance status (PS) could be conserved or even improved in many cases. Patients with lung function impairment, as well as patients with other disease-related symptoms obtained additional therapy benefits.
Adenocarcinoma↗
Gefitinib ("Iressa"): a new therapy for advanced non-small-cell lung cancer.
Patients with advanced non-small-cell lung cancer (NSCLC) have a poor prognosis and suffer many disease-related symptoms. Treatments should therefore aim to palliate these symptoms as well as improve overall quality of life. Gefitinib ("Iressa") is a novel epidermal growth factor receptor tyrosine kinase inhibitor that targets cell signaling involved in tumor growth and differentiation. In Phase II trials in recurrent NSCLC, gefitinib provided objective responses and symptom relief, and was generally well tolerated. Now approved for the treatment of advanced NSCLC in over 25 countries, including Japan and the USA, gefitinib has demonstrated significant clinical benefit in a disease area with limited treatment options.
Antineoplastic Agents↗
Pemetrexed-cisplatin combination in mesothelioma.
Despite the desperate struggle for improvement in the therapy of malignant pleural mesothelioma in previous decades, no standard therapy could be established. Pemetrexed (Alimta), a new multitargeted antifolate, showed significant antitumor activity in combination with cisplatin compared with cisplatin alone in patients with unresectable pleural mesothelioma. Furthermore, this improved efficacy was transformed into a significant symptomatic benefit. These data led to the approval of the drug by the US Food and Drug Administration and recently by the European Medicines Evaluation Agency for this combination in malignant pleural mesothelioma, and consequently founded the first standard of treatment in this disease. This review reflects the development of chemotherapy in malignant pleural mesothelioma, discusses the results of the EMPHACIS trial, and outlines further developments for pemetrexed-containing regimens in malignant pleural mesothelioma.
Antineoplastic Combined Chemotherapy Protocols↗
A pilot trial of gefitinib in combination with docetaxel in patients with locally advanced or metastatic non-small-cell lung cancer.
Despite improvements in conventional treatment, patients with advanced non-small-cell lung cancer (NSCLC) have a poor prognosis, leaving a significant unmet need for novel treatments. One such novel, biologically targeted agent is the orally active epidermal growth factor receptor tyrosine kinase inhibitor gefitinib. This open-label pilot trial investigated the safety, pharmacokinetics, and efficacy of 2 doses of gefitinib (250 and 500 mg per day) combined with docetaxel (75 mg/m2) in patients with locally advanced or metastatic NSCLC as first- and second-line chemotherapy. Eighteen patients were recruited: 6 received gefitinib 250 mg per day plus docetaxel; 12 received gefitinib 500 mg per day plus docetaxel. Combination therapy was feasible with no overlapping toxicities. No patients experienced dose-limiting toxicities (DLTs) at 250 mg per day; 1 patient had 2 DLT events at 500 mg per day (grade 3 rash and diarrhea for >4 days). Adverse events were mild to moderate, including fatigue, mucositis, nausea, anorexia, rash, diarrhea, and fever. Docetaxel did not appear to alter steady-state exposure to gefitinib. The effect of gefitinib on exposure to docetaxel was equivocal; with the exception of 2 patients in the gefitinib 250 mg per day dose group, there appeared to be no trend toward a higher or lower exposure to docetaxel when given in the presence of gefitinib compared with that when given alone. Combination therapy was associated with antitumor activity and responses were seen with gefitinib in 2 of 6 patients at 250 mg per day and 4 of 12 patients at 500 mg per day. This combination is feasible and has an acceptable and predictable safety profile, as well as associated antitumor activity.
Administration, Oral↗
Randomized multicenter phase II study of gemcitabine versus docetaxel as first-line therapy with second-line crossover in advanced-stage non-small-cell lung cancer.
BACKGROUND: A randomized phase II study was performed to determine whether single-agent gemcitabine or docetaxel with the introduction of the opposite agent in case of disease progression (ie, in the second-line setting) is feasible and effective in chemotherapy-naive patients with advanced non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: The doses were 1,000 mg/m2 for gemcitabine and 35 mg/m2 for docetaxel, each given on days 1, 8, and 15 every 4 weeks. After a planned interim analysis, the docetaxel/gemcitabine arm (ie, docetaxel followed by gemcitabine) was closed after enrollment of 49 patients because of poor predefined feasibility. A total of 98 patients were recruited to the gemcitabine/docetaxel arm (ie, gemcitabine followed by docetaxel). RESULTS: Quality of life remained near baseline levels during the administration of 6 cycles of gemcitabine/docetaxel chemotherapy, whereas it deteriorated after 2 cycles of docetaxel/gemcitabine. Toxicity was comparable between arms. Median times to progression were 4.3 months and 2.2 months with gemcitabine/docetaxel and docetaxel/gemcitabine, respectively, and median overall survival times were 9 months (gemcitabine/docetaxel) and 5 months (docetaxel/gemcitabine; P=0.029, Wilcoxon rank-sum test). CONCLUSION: These results indicate that first-line gemcitabine followed by second-line weekly docetaxel is feasible, with promising survival in patients with advanced NSCLC.
Adult↗
Randomized phase III trial of pemetrexed versus docetaxel in patients with non-small-cell lung cancer previously treated with chemotherapy.
PURPOSE: To compare the efficacy and toxicity of pemetrexed versus docetaxel in patients with advanced non-small-cell lung cancer (NSCLC) previously treated with chemotherapy. PATIENTS AND METHODS: Eligible patients had a performance status 0 to 2, previous treatment with one prior chemotherapy regimen for advanced NSCLC, and adequate organ function. Patients received pemetrexed 500 mg/m(2) intravenously (i.v.) day 1 with vitamin B(12), folic acid, and dexamethasone or docetaxel 75 mg/m(2) i.v. day 1 with dexamethasone every 21 days. The primary end point was overall survival. RESULTS: Five hundred seventy-one patients were randomly assigned. Overall response rates were 9.1% and 8.8% (analysis of variance P =.105) for pemetrexed and docetaxel, respectively. Median progression-free survival was 2.9 months for each arm, and median survival time was 8.3 versus 7.9 months (P = not significant) for pemetrexed and docetaxel, respectively. The 1-year survival rate for each arm was 29.7%. Patients receiving docetaxel were more likely to have grade 3 or 4 neutropenia (40.2% v 5.3%; P <.001), febrile neutropenia (12.7% v 1.9%; P <.001), neutropenia with infections (3.3% v 0.0%; P =.004), hospitalizations for neutropenic fever (13.4% v 1.5%; P <.001), hospitalizations due to other drug related adverse events (10.5% v 6.4%; P =.092), use of granulocyte colony-stimulating factor support (19.2% v 2.6%, P <.001) and all grade alopecia (37.7% v 6.4%; P <.001) compared with patients receiving pemetrexed. CONCLUSION: Treatment with pemetrexed resulted in clinically equivalent efficacy outcomes, but with significantly fewer side effects compared with docetaxel in the second-line treatment of patients with advanced NSCLC and should be considered a standard treatment option for second-line NSCLC when available.
Adult↗
Gefitinib in combination with gemcitabine and cisplatin in advanced non-small-cell lung cancer: a phase III trial--INTACT 1.
PURPOSE: The purpose of this study was to determine whether the addition of the epidermal growth factor receptor tyrosine kinase inhibitor gefitinib (Iressa, ZD1839; AstraZeneca, Wilmington, DE) to standard first-line gemcitabine and cisplatin provides clinical benefit over gemcitabine and cisplatin alone in patients with advanced or metastatic non-small-cell lung cancer (NSCLC). Gefitinib has demonstrated encouraging efficacy in advanced NSCLC in phase II trials in pretreated patients, and a phase I trial of gefitinib in combination with gemcitabine and cisplatin showed favorable tolerability. PATIENTS AND METHODS: This was a phase III randomized, double-blind, placebo-controlled, multicenter trial in chemotherapy-naive patients with unresectable stage III or IV NSCLC. All patients received up to six cycles of chemotherapy (cisplatin 80 mg/m(2) on day 1 and gemcitabine 1,250 mg/m(2) on days 1 and 8 of the 3-week cycle) plus either gefitinib 500 mg/d, gefitinib 250 mg/d, or placebo. Daily gefitinib or placebo was continued until disease progression. End points included overall survival (primary), time to progression, response rates, and safety evaluation. RESULTS: A total of 1,093 patients were enrolled. There was no difference in efficacy end points between the treatment groups: for the gefitinib 500 mg/d, gefitinib 250 mg/d, and placebo groups, respectively, median survival times were 9.9, 9.9, and 10.9 months (global ordered log-rank [GOLrank] P =.4560), median times to progression were 5.5, 5.8, and 6.0 months (GOLrank; P =.7633), and response rates were 49.7%, 50.3%, and 44.8%. No significant unexpected adverse events were seen. CONCLUSION: Gefitinib in combination with gemcitabine and cisplatin in chemotherapy-naive patients with advanced NSCLC did not have improved efficacy over gemcitabine and cisplatin alone. The reasons for this remain obscure and require further preclinical testing.
Adult↗
Chemotherapy in stage-IV NSCLC.
Since cisplatin-based chemotherapy was proven to increase survival in advanced and metastatic NSCLC various new combinations have been tested. The third generation regimens which showed almost comparable efficacy among each other in randomised trials often proved a better response rate and time to progression combined with a remarkable reduction of toxic side effects compared to "classic" combinations, whereas most studies only noted a modest increase in survival. Two-drug regimens were more effective than monotherapy but at the expense of significantly increased toxicity, while monotherapy compared to BSC improved quality of life and survival. The novel antifolate Pemetrexed proved comparable activity to docetaxel with significantly reduced toxicities.
Antineoplastic Combined Chemotherapy Protocols↗
Pemetrexed in malignant pleural mesothelioma.
Malignant pleural mesothelioma (MPM) is a disease with a poor prognosis, related in part to the aggressiveness of this disease, and in part due to the lack of drugs that have demonstrated tumor activity. Historically, antifolates such as methotrexate have been the most active drugs in the treatment of mesothelioma. Newer antifolates have recently demonstrated higher efficacy than older regimens in the treatment of this rare disease. One of these agents, pemetrexed (Alimta), has been evaluated both as a single agent and as part of a combination regimen. Pemetrexed has been studied in three trials in patients with MPM, and two phase I trials included patients with MPM. In a phase II trial, pemetrexed was studied as a single agent in patients with MPM. Seven of 64 patients achieved partial responses, with a median overall survival of 10.7 months. A large, randomized, phase III trial was conducted to compare pemetrexed/cisplatin with cisplatin. The response rate was 41.3% compared with 16.7%, median survival was 12.1 months compared with 9.3 months, and 1-year survival was 50.3% vs 38% in the pemetrexed/cisplatin and cisplatin arms, respectively. The combination of pemetrexed/cisplatin also demonstrated superiority in quality of life and pulmonary functioning analysis when compared with cisplatin.
Antineoplastic Combined Chemotherapy Protocols↗
Randomized phase III trial of paclitaxel, etoposide, and carboplatin versus carboplatin, etoposide, and vincristine in patients with small-cell lung cancer.
BACKGROUND: Paclitaxel administered in combination with a topoisomerase-II inhibitor (such as etoposide) and carboplatin is an effective and safe first-line treatment for patients with small-cell lung cancer (SCLC). We conducted a randomized phase III multicenter trial to determine whether paclitaxel plus etoposide plus carboplatin improves the outcome of patients with primary SCLC relative to standard chemotherapy (carboplatin, etoposide, and vincristine). METHODS: Between January 1998 and December 1999, 614 patients with SCLC stages I-IV were randomly assigned to the standard arm (309 patients) or the experimental arm (305 patients). Treatment courses were repeated every 21 days for a maximum of six courses. All patients were evaluated for response rate, survival, and toxicities every two courses. The primary endpoint was survival. Survival curves were estimated with the Kaplan-Meier method and compared using the log-rank test. All statistical tests were two-sided. RESULTS: A total of 608 patients were evaluable for all endpoints (standard arm 307 patients, experimental arm 301 patients). The hazard ratio [HR] of death for patients receiving the standard treatment was statistically significantly higher than that for patients receiving the experimental treatment (HR = 1.22, 95% confidence interval [CI] = 1.03 to 1.45; P =.024). Progression-free survival was also statistically significantly shorter for patients in the standard arm relative to that of patients in the experimental arm (HR = 1.21, 95% CI = 1.03 to 1.42). There were no differences in the response rates (complete and partial combined) to the treatments (standard arm: 69.4%, 95% CI = 63.9% to 74.5%; experimental arm: 72.1%, 95% CI = 66.7% to 77.1%; difference = 2.7%, 95% CI = 4.5% to 9.9%). Rates of severe grade of anemia, leukocytopenia, neutropenia, and thrombocytopenia were lower in the experimental arm than in the standard arm. CONCLUSION: Patients with previously untreated SCLC who received paclitaxel, etoposide, and carboplatin showed improved overall and progression-free survival and less frequent hematologic toxicities than those who received the standard therapy.
Adult↗