Economic evaluation of three two-drug chemotherapy regimens in advanced non-small-cell lung cancer.

BACKGROUND: During the 1990s, a number of new cytotoxic agents with clinically relevant activity in non-small-cell lung cancer (NSCLC), and with a more favourable therapeutic index than drugs already in use, became available. Given the high prices of these new drugs and the large number of patients affected, it is important to compare the relative benefits and costs of these treatments with the existing regimens before treatment policy decisions are changed. PURPOSE: An economic evaluation of three different regimens of chemotherapy in patients with advanced NSCLC was performed from the perspective of the Dutch health insurance system using tariffs valid for 2002. The economic evaluation was integrated into a phase III clinical trial in which the reference regimen cisplatin-paclitaxel was compared with two experimental regimens: cisplatin-gemcitabine and gemcitabine-paclitaxel. MATERIALS AND METHODS: Unit costs were applied to resource use data collected prospectively on case report forms during the trial. The average total (uncensored) cost per patient was determined for each of the treatment groups. The principal outcome measure for the economic evaluation was the estimated mean survival time per treatment group. This outcome was then incorporated into incremental cost-effectiveness ratios based on costs corrected for censoring. The impact of uncertainty was assessed by bootstrap techniques, and the analysis and interpretation of the data focused on the bivariate density of differences in outcomes and costs in the incremental cost-effectiveness plane. The final results were summarised by the derivation of cost-effectiveness acceptability curves. RESULTS: The estimated mean survival time was equivalent in the two cisplatin-based regimens with largely overlapping confidence intervals. There was a 99% probability that cisplatin-gemcitabine is the least costly regimen of the two and a 72% probability that this regimen reduces costs while at the same time improving survival. Compared with cisplatin-paclitaxel, the gemcitabine-paclitaxel regimen engendered a borderline significant reduction in mean survival time combined with an almost 90% probability of an increase in costs. CONCLUSION: The two cisplatin-based regimens are equivalent in terms of survival, but cisplatin-gemcitabine may reduce costs by approximately 2000 Euros patient compared with cisplatin-paclitaxel. Gemcitabine-paclitaxel is a dominated option with higher costs and a reduction in mean survival time compared with cisplatin-paclitaxel.

Impact of emesis on clinical and economic outcomes of cancer therapy with highly emetogenic chemotherapy regimens: a retrospective analysis of three clinical trials.

OBJECTIVE: It is a current hypothesis that chemotherapy-induced nausea and vomiting (CINV) may ultimately impede the clinical success of cancer treatments by hindering patients' adherence to the optimal treatment schedule. The aim of this study is to examine clinical trial data retrospectively for possible evidence of such a detrimental impact of CINV. PATIENTS AND METHODS: Data from three recent European Organization for Research and Treatment of Cancer (EORTC) trials of highly emetogenic cisplatin-based chemotherapy in diverse patient populations were analyzed retrospectively for incidence and possible impact of CINV. Data on the incidence of emesis are presented as simple descriptive analyses, while the hypothetical impact of CINV on clinical outcomes and on the patients' length of hospital stays is analyzed by means of multivariate regression analysis techniques to control for confounding variables. MAIN RESULTS: Between 42 and 59% of the patients in the trials experienced at least one episode of nausea of NCIC grade 2 or worse, while the incidence of vomiting of similar grade was between 31 and 58%. Only in one of the trials could the determinants of the adherence to protocol therapy be assessed, statistically significant variables were the severity of emesis (p < 0.0001) and other toxicities combined (p < 0.019). In turn, a Cox regression showed adherence to protocol therapy and other toxicities as the only statistically significant determinants of overall survival. CONCLUSIONS: This study has shown a discernible detrimental impact of CINV on patients' adherence to protocol therapy and, indirectly, on survival in one of the three trials examined. Further studies are required to substantiate this finding.

Three-arm randomized study of two cisplatin-based regimens and paclitaxel plus gemcitabine in advanced non-small-cell lung cancer: a phase III trial of the European Organization for Research and Treatment of Cancer Lung Cancer Group--EORTC 08975.

PURPOSE: To compare the therapeutic efficacy of paclitaxel plus cisplatin (arm A) versus gemcitabine plus cisplatin (arm B) and arm A versus paclitaxel plus gemcitabine (arm C) in chemotherapy-naive patients with advanced non-small-cell lung cancer (NSCLC). MATERIALS AND METHODS: Patients were randomly assigned to receive either paclitaxel 175 mg/m2 (3-hour infusion, day 1) or gemcitabine 1,250 mg/m2 (days 1 and 8) both combined with cisplatin 80 mg/m2 (day 1) or paclitaxel 175 mg/m2 (3-hour infusion, day 1) combined with gemcitabine 1,250 mg/m2 (days 1 and 8). Primary end point was comparison of overall survival for B versus A and C versus A. Secondary end points included response rate and duration, progression-free survival, toxicities, quality of life [QoL], and cost of treatment. RESULTS: Four hundred eighty patients (arm A, 159; arm B, 160; arm C, 161 patients) were enrolled; all baseline characteristics were balanced. Median survival times were as follows: arm A, 8.1 months; arm B, 8.9 months; arm C, 6.7 months. Response rates were 31.8% for arm A, 36.6% for arm B, and 27.7% for arm C. Other than myelosuppression (B v A, P <.005), no statistically or clinically significant differences were observed for secondary end points. The average treatment costs were 25% higher in arm C as compared with arms A and B. CONCLUSION: Gemcitabine plus cisplatin and paclitaxel plus gemcitabine do not increase overall survival in patients with advanced NSCLC as compared with paclitaxel plus cisplatin. Treatment was well tolerated, and most QoL parameters were similar, but costs associated with the nonplatinum arm were highest.

Cost effectiveness of paclitaxel/cisplatin compared with cyclophosphamide/cisplatin in the treatment of advanced ovarian cancer in Belgium.

OBJECTIVE: To assess the economic impact of two polychemotherapy regimens for patients with advanced ovarian cancer from the perspective of the Belgian health insurance and financing system. DESIGN: An economic evaluation was integrated in an intergroup randomised controlled trial (EORTC 55931) in which patients were randomised to receive the new treatment of paclitaxel and cisplatin or the standard therapy of cyclophosphamide and cisplatin. Data on the use of medical resources were collected prospectively for the 231 European Organization for Research and Treatment of Cancer (EORTC) patients in the trial and costs were valued by using unit prices. The outcome for the economic evaluation was mean survival time as determined by the so-called restricted means method, with the time point of restriction fixed by statistical criteria. A correction of censoring of the cost data collected in the trial was also performed. MAIN OUTCOME MEASURES AND RESULTS: The paclitaxel and cisplatin group experienced a statistically significant improvement in mean survival time of 4 months, which was associated with an increase in the average total cost per patient of 6795 euros (EUR; 1998 values), when costs were assessed over the same period as the gain in mean survival time. This corresponds to a point estimate of the incremental cost-effectiveness ratio of EUR20 385 per life-year gained. The impact of uncertainty was assessed by using a bias-corrected and accelerated bootstrap method with 5000 resamples, and the final results of the analysis are expressed in terms of a cost-effectiveness acceptability curve. CONCLUSIONS: The present economic evaluation has shown that the substitution of paclitaxel for cyclophosphamide in the chemotherapy regimen for women with advanced ovarian cancer leads to a significant improvement in patient survival, which is associated with an increase in costs for the Belgian health insurance system.