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Pharmaco-economic evaluations become more important for the reimbursement of pharmaceuticals, and will be obligatory for new pharmaceutical drugs for which an added therapeutic value is claimed and a price premium is proposed by the manufacturer. Therefore, it is important to guide purchasers and providers of pharmaceutical care in their efforts related to the evaluation process. Standard Report Format can support the quality, transparency and exhaustiveness of the data submitted. A multidisciplinary task force developed a Standard Report Format for pharmaco-economic evaluations in Belgium.

Background: The efficacy and toxicity of the combination of two cytotoxic compounds that are active as single agents in non-small cell lung cancer (NSCLC), paclitaxel (Taxol) and carboplatin (Paraplatin) was investigated in a multicenter, community-based setting., Materials and Methods: Two consecutive cohorts of chemonaive patients with stages IIIA/B and IV NSCLC received two dose levels of paclitaxel. The first cohort received 200 mg/m2 over 3 hours (HD) and the second cohort 175 mg/m2 over 3 hours (LD) in combination with a fixed dose of carboplatin. The dose of carboplatin was calculated according to the Calvert formula with an area under the concentration versus time curve (AUC) value of 6 mg/ml/minute. The carboplatin clearance, calculated by the Chatelut formula rather than the glomerulation filtration rate (GFR) +25, was introduced into the Calvert formula. The eligibility criteria were identical for both cohorts throughout the study. Treatment was administered every three weeks. The study endpoints were response rate (RR), toxicity, time to progression (TTP) and survival (S)., Results: One hundred and thirty consecutive eligible patients from 36 Belgian institutions were fully evaluable for all study parameters (99 in the HD and 31 in the LD cohort). Myelosuppression was the most prominent side-effect of treatment with comparable results for both cohorts. The worst grade 3-4 leucopenia and neutropenia per patient in the HD versus LD cohort was 34.4 vs 19.3% and 59.2 vs 51.6%, respectively. 10.4% of patients in the HD cohort required hospitalisation for febrile neutropenia (6.2% with and 4.2% without documented bacterial infection), while in the LD cohort the respective figures were 13.7, 10.3 and 3.4%. The most prominent non-hematologic toxicities were alopecia and polyneuropathy, with no major difference between the HD and LD cohort (grade 2 alopecia in 78.1 vs. 83.9% and grade 3 neuropathy in 14.3 vs. 9.7%, respectively). The overall best clinical RR was 31 out of 130 (23.8%) with one complete (CR) and 30 partial responses (PR). The respective RR in the HD and LD cohort was 23.2 and 25.8%. Median TTP and S for all patients was 120 and 248 days, with no apparent difference between the HD and the LD cohort (119 and 254 versus 128 and 222, respectively). The one year survival was 34% in the HD cohort. The 95% confidence intervals for efficacy and toxicity parameters overlapped in both cohorts., Conclusion: In this multicenter study, the combination of paclitaxel and carboplatin produced a moderate RR of 23.8% in stages IIIA/B & IV NSCLC. The therapy was generally well tolerated at both doses of paclitaxel. Myelosuppression, neurotoxicity and alopecia were the major therapy-related side-effects. The differences between the two paclitaxel dose cohorts with respect to activity and toxicity were minimal. The use of the Chatelut formula to calculate the carboplatin clearance is feasible, but might have lead to the apparent excess in myelotoxicity in our study compared to other studies which used other methods for estimating renal function.