Prospective Randomized Trial of Docetaxel Versus Best Supportive Care in Patients With Non–Small-Cell Lung Cancer Previously Treated With Platinum-Based Chemotherapy

2000 ◽  
Vol 18 (10) ◽  
pp. 2095-2103 ◽  
Author(s):  
Frances A. Shepherd ◽  
Janet Dancey ◽  
Rodryg Ramlau ◽  
Karin Mattson ◽  
Richard Gralla ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Supportive Care ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Best Supportive Care ◽  
Small Cell ◽  
Rank Test ◽  
Small Cell Lung ◽  
Log Rank Test ◽  
Platinum Based Chemotherapy

PURPOSE: To evaluate whether treatment with single-agent docetaxel would result in longer survival than would best supportive care in patients with non–small-cell lung cancer who had previously been treated with platinum-based chemotherapy. Secondary end points included assessment of response (docetaxel arm only), toxicity, and quality of life. PATIENTS AND METHODS: Patients with performance statuses of 0 to 2 and stage IIIB/IV non–small-cell lung cancer with either measurable or evaluable lesions were eligible for entry onto the study if they had undergone one or more platinum-based chemotherapy regimens and if they had adequate hematology and biochemistry parameters. They were excluded if they had symptomatic brain metastases or if they had previously been treated with paclitaxel. Patients were stratified by performance status and best response to cisplatin chemotherapy and were then randomized to treatment with docetaxel 100 mg/m2 (49 patients) or 75 mg/m2 (55 patients) or best supportive care. Patients in both arms were assessed every 3 weeks. RESULTS: One hundred four patients (103 of whom were eligible for entry onto the study) were well balanced for prognostic factors. Of 84 patients with measurable lesions, six (7.1%) achieved partial responses (three patients at each dose level). Time to progression was longer for docetaxel patients than for best supportive care patients (10.6 v 6.7 weeks, respectively; P < .001), as was median survival (7.0 v 4.6 months; log-rank test, P = .047). The difference was more significant for docetaxel 75 mg/m2 patients, compared with corresponding best supportive care patients (7.5 v 4.6 months; log-rank test, P = .010; 1-year survival, 37% v 11%; χ2 test, P = .003). Febrile neutropenia occurred in 11 patients treated with docetaxel 100 mg/m2, three of whom died, and in one patient treated with docetaxel 75 mg/m 2 . Grade 3 or 4 nonhematologic toxicity, with the exception of diarrhea, occurred at a similar rate in both the docetaxel and best supportive care groups. CONCLUSION: Treatment with docetaxel is associated with significant prolongation of survival, and at a dose of 75 mg/m2, the benefits of docetaxel therapy outweigh the risks.

Randomized Phase III Trial of Docetaxel Versus Vinorelbine or Ifosfamide in Patients With Advanced Non–Small-Cell Lung Cancer Previously Treated With Platinum-Containing Chemotherapy Regimens

2000 ◽  
Vol 18 (12) ◽  
pp. 2354-2362 ◽  
Author(s):  
Frank V. Fossella ◽  
Russell DeVore ◽  
Ronald N. Kerr ◽  
Jeffrey Crawford ◽  
Ronald R. Natale ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Phase Iii ◽  
Control Treatment ◽  
Rank Test ◽  
Small Cell Lung ◽  
Phase Iii Trial ◽  
Platinum Based Chemotherapy

PURPOSE: To confirm the promising phase II results of docetaxel monotherapy, this phase III trial was conducted of chemotherapy for patients with advanced non–small-cell lung cancer (NSCLC) who had previously failed platinum-containing chemotherapy. PATIENTS AND METHODS: A total of 373 patients were randomized to receive either docetaxel 100 mg/m2 (D100) or 75 mg/m2 (D75) versus a control regimen of vinorelbine or ifosfamide (V/I). The three treatment groups were well-balanced for key patient characteristics. RESULTS: Overall response rates were 10.8% with D100 and 6.7% with D75, each significantly higher than the 0.8% response with V/I (P = .001 and P = .036, respectively). Patients who received docetaxel had a longer time to progression (P = .046, by log-rank test) and a greater progression-free survival at 26 weeks (P = .005, by χ2 test). Although overall survival was not significantly different between the three groups, the 1-year survival was significantly greater with D75 than with the control treatment (32% v 19%; P = .025, by χ2 test). Prior exposure to paclitaxel did not decrease the likelihood of response to docetaxel, nor did it impact survival. There was a trend toward greater efficacy in patients whose disease was platinum-resistant rather than platinum-refractory and in patients with performance status of 0 or 1 versus 2. Toxicity was greatest with D100, but the D75 arm was well-tolerated. CONCLUSION: This first randomized trial in this setting demonstrates that D75 every 3 weeks can offer clinically meaningful benefit to patients with advanced NSCLC whose disease has relapsed or progressed after platinum-based chemotherapy.

Economic Analysis of the TAX 317 Trial: Docetaxel Versus Best Supportive Care as Second-Line Therapy of Advanced Non–Small-Cell Lung Cancer

2002 ◽  
Vol 20 (5) ◽  
pp. 1344-1352 ◽  
Author(s):  
Natasha B. Leighl ◽  
Frances A. Shepherd ◽  
Rita Kwong ◽  
Ronald L. Burkes ◽  
Ronald Feld ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Health Care ◽  
Supportive Care ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Best Supportive Care ◽  
Small Cell ◽  
Second Line ◽  
Small Cell Lung ◽  
The Cost

PURPOSE: To determine the cost-effectiveness (CE) of second-line docetaxel compared with best supportive care (BSC) in the TAX 317 trial, a randomized clinical trial of second-line chemotherapy in non–small-cell lung cancer. METHODS: A retrospective CE analysis of the TAX 317 trial was undertaken, evaluating direct medical costs of therapy from the viewpoint of Canada’s public health care system. Costs were derived in 1999 Canadian dollars, and resource use was determined through prospective trial data. RESULTS: The incremental survival benefit in the docetaxel arm over BSC was 2 months (P = .047). The CE of docetaxel was $57,749 per year of life gained. For patients treated with docetaxel 75 mg/m2, the CE was $31,776 per year of life gained. In univariate sensitivity analyses, CE estimates were most sensitive to changes in survival, ranging from $18,374 to $117,434 with 20% variation in survival at the recommended dose. The largest cost center in both arms was hospitalization, followed by the cost of drugs, investigations, radiotherapy, and community care. BSC patients had fewer hospitalizations than patients in the chemotherapy arm and were more often palliated at home. CONCLUSION: Although the decision to treat should not be based on economic considerations alone, our CE estimate of $31,776 per year of life gained (at the currently recommended dose of docetaxel) is within an acceptable range of health care expenditures, and the total costs of therapy are similar to those of second-line palliative chemotherapy for other solid tumors.

MDM2 Polymorphism, Survival, and Histology in Early-Stage Non–Small-Cell Lung Cancer

2007 ◽  
Vol 25 (16) ◽  
pp. 2243-2247 ◽  
Author(s):  
Rebecca Suk Heist ◽  
Wei Zhou ◽  
Lucian R. Chirieac ◽  
Thea Cogan-Drew ◽  
Geoffrey Liu ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Squamous Cell ◽  
Cell Lung Cancer ◽  
Early Stage ◽  
Small Cell ◽  
Rank Test ◽  
Small Cell Lung ◽  
Log Rank Test ◽  
Mdm2 Polymorphism

Purpose MDM2 is a negative regulator of p53. The MDM2 309T/G polymorphism has been associated with differential MDM2 expression levels and inhibition of the p53 pathway. We hypothesized that the MDM2 G/G genotype may be associated with worse survival outcomes in lung cancer, especially in squamous cell cancers where p53 abnormalities are more common. Patients and Methods We evaluated the relationship between MDM2 polymorphism status and overall survival (OS) among patients with early-stage non–small-cell lung cancer (NSCLC) treated with surgical resection at Massachusetts General Hospital from 1992 to 2000. Kaplan-Meier methods and the log-rank test were used to compare survival by polymorphism status. Cox proportional hazards models were used to adjust for possible confounding variables. Results There were 383 patients in the analysis. In the early-stage population as a whole, the G/G genotype seemed to be associated with worse OS on adjusted analysis (adjusted hazard ratio = 1.57; 95% CI, 1.03 to 2.40; P = .04). Among patients with squamous histology, OS was significantly worse among those with the G/G genotype (P = .0001 by log-rank test), with 5-year survival rates among the genotypes of 59% for T/T, 53% for T/G, and 7% for G/G. Conclusion Our findings suggest that the G/G genotype of the MDM2 polymorphism is associated with worse OS among early-stage NSCLC patients, particularly those with squamous cell histology.

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