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

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Abstract

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 cisplatinpaclitaxel 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 cisplatinbased 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 per patient compared with cisplatin-paclitaxel. Gemcitabine-paclitaxel is a dominated option with higher costs and a reduction in mean survival time compared with cisplatinpaclitaxel.

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Notes

  1. In the SW quadrant, λ should be interpreted as the reduction in costs that the decision maker requires in order to accept a deterioration of survival.

  2. Comparison with the examination of the choice of first treatment modality for second-line therapy, which was quite similar across the treatment groups.

  3. From the three hospitals recruiting most patients to the trial (37% of the total), we have received claims data, i.e. the hospital electronic files recording (in principle) all the resources used and procedures performed for the patients during hospital stays or outpatient consultations. We are preparing an analysis to compare the direct medical costs as determined from the claims data and the costs determined on the basis of the data recorded in the case report forms of the clinical trial.

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Acknowledgements

The authors would like to thank Marie-Ange Lentz of the EORTC Data Center for data management, Catherine Legrand of the EORTC Data Center for the statistical analysis of the clinical data, and Dr G. Giaccone in his capacity as chairman for the EORTC Lung Group during the period of the study. We also thank Bristol-Myers-Squibb and Eli Lilly for providing Taxol® (paclitaxel) and Gemzar® (gemcitabine) as investigational agents free of charge.

The authors would like to acknowledge the important contribution to patient accrual of the following investigators: F. Schramel (St. Antonius Ziekenhuis, Nieuwegein, The Netherlands); H. Smit (Rijnstate Hospital, Arnhem, The Netherlands); R. Gaafar (National Cancer Institute, Cairo, Egypt); B. Biesma (Bosch Medicentrum, s’Hertogenbosch, The Netherlands); C. Manegold (Thoraxklinik, Heidelberg, Germany); M. Koolen (Academisch Medisch Centrum, Amsterdam, The Netherlands); F. Wilschut (Ziekenhuis Gelderse Vallei, Bennekom, The Netherlands); J. Stigt (Sophia Ziekenhuis, Zwolle, The Netherlands); A. Van Bochove (Ziekenhuis De Heel, Zaandam, The Netherlands); W. Pieters (Elkerliek Ziekenhuis, Helmond, The Netherlands); N.J.J. Schlosser (Universitair Medisch Centrum, Utrecht, The Netherlands); A. Price (Western General Hospital, Edinburgh, UK); R. Schipper (Catharina Ziekenhuis, Eindhoven, The Netherlands); M-A. Haller (CHRU De Nancy — Hopitaux de Brabois, Nancy, France); A. Lukker (St. Maartens Gasthuis, Venlo, The Netherlands); J. Bozzino (Newcastle General Hospital, Newcastle-upon-Tyne, UK); N. Van Walree (Ziekenhuis De Baronie, Breda, The Netherlands); H. Belderbos (St. Ignatius Ziekenhuis, Breda, The Netherlands); P. Zatloukal (University Hospital Bulovka, Prague, Czech Republic); M. Möllers (Gelre Ziekenhuizen — Lukas locatie, Apeldoorn, The Netherlands), H. Dik (Rijnland Ziekenhuis, Leiderdorp, The Netherlands); V. Spataro (Ospedale San Giovanni, Bellinzona, Switzerland); H.B. Kwa (Onze Lieve Vrouw Gasthuis, Amsterdam, The Netherlands); D. Galdermans (Algemeen Ziekenhuis Middelheim, Antwerpen, Belgium); L. Willems (Leiden University Medical Centre, Leiden, The Netherlands); B. Rapoport (The Medical Oncology Centre of Rosebank, South Africa).

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Authors and Affiliations

  1. Health Economics Unit, European Organisation for Research and Treatment of Cancer, Brussels, Belgium

    Niels Neymark

  2. Medical Oncology, Matero, Spain

    Pilar Lianes

  3. Vrije Universiteit Medical Center, Amsterdam, The Netherlands

    Egbert F. Smit

  4. Martini Hospital, Groningen, The Netherlands

    Egbert F. Smit

  5. Erasmus MC, Rotterdam, The Netherlands

    Jan P. van Meerbeeck

  6. University Hospital Ghent, Ghent, Belgium

    Jan P. van Meerbeeck

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  1. Niels Neymark
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  2. Pilar Lianes
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  3. Egbert F. Smit
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  4. Jan P. van Meerbeeck
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Corresponding author

Correspondence to Niels Neymark.

Appendix 1: Assumptions Regarding Antiemetic Regimens

Appendix 1: Assumptions Regarding Antiemetic Regimens

The cisplatin regimens used (80 mg/m2) are highly emetogenic. That is, they are at level 5 of the scale by Berger and Clark-Snow,[24] which indicates the emetogenic potential of chemotherapeutic agents. Both paclitaxel and gemcitabine are level 2, so their combination should be level 3, moderately emetogenic, with emesis induced in 30–60% of the patients. At level 5, >90% of the patients experience emesis. As the case report forms were not intended to record the regimens and the doses of antiemetics used, the cost calculations must proceed based on assumptions.

Based on a review of the literature, and especially the survey by Sanchez et al.,[25] we have assumed the regimens described below. These are partly adapted to the varying emetogenicity of the chemotherapy agents used.

  • Cisplatin-paclitaxel: IV dexamethasone 20mg + IV ondansetron 8mg and then 24 mg/day orally for 3 days.

  • Cisplatin-gemcitabine: IV dexamethasone 20mg + IV ondansetron 8mg and then 24 mg/day orally for 3 days.

  • Gemcitabine-paclitaxel: IV dexamethason 20mg + IV ondansetron 8mg and then 12 mg/day orally for 3 days.

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Neymark, N., Lianes, P., Smit, E.F. et al. Economic evaluation of three two-drug chemotherapy regimens in advanced non-small-cell lung cancer. Pharmacoeconomics 23, 1155–1166 (2005). https://doi.org/10.2165/00019053-200523110-00007

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