Cost-effectiveness analysis of breast cancer adjuvant treatment: FEC 50 versus FEC 100 (FASG05 study).

BACKGROUND: The aim of the study was to assess the incremental cost-effectiveness ratio (ICER) of the FEC 100 compared with the FEC 50 in the FASG05 trial. MATERIALS AND METHODS: A cost-effectiveness analysis was performed using a multi-state Markov process model. Relevant clinical data introduced into the model were obtained from 10-year follow-up of the clinical trial FASG05. Survival curves for each health state were assessed by survival parametric model. The model allowed assessments from the start of adjuvant chemotherapy until death. The costs of adjuvant treatment and follow-up were estimated. The costs of recurrence were evaluated from the medical records of 146 patients. A prospective survey was performed on a cohort of 87 patients to quantify the resources external to the hospital (including cost of transportation). The inpatient costs were evaluated using the French diagnosis-related groups. The ambulatory costs were assessed using the French nomenclature. Costs were expressed in 2002 Euro (), according to the French societal perspective. The ICER assessed the cost of one additional life year saved. A discount rate of 5% per year was used for cost, and alternatively 0%, 3% and 5% for effectiveness. We validated the results with a probabilistic sensitivity analysis incorporating parametric and non-parametric bootstraps, and with the acceptability curves. RESULTS: The mean total discounting cost of adjuvant treatments was 11 465 for FEC 50 and 13 815 for FEC 100; the mean total discounting cost of recurrences was 14 636 and 13 503, respectively. According to the discount rate of effectiveness, the life expectancy was 16.5, 11.4 and 9.3 years for FEC 50 and 18.4, 12.5 and 10.2 years for FEC 100. The ICER (cost per life year saved) were 642, 1084 and 1460, respectively. The probability according to which FEC 50 is strictly dominated by FEC 100 was 0.15. CONCLUSION: The clinical benefit of FEC 100 generates a negligible cost increase when compared with FEC 50.

Phase II multicentre randomised study of docetaxel plus epirubicin vs 5-fluorouracil plus epirubicin and cyclophosphamide in metastatic breast cancer.

The purpose of the study was to evaluate the efficacy and safety of docetaxel plus epirubicin (ET) and of 5-fluorouracil plus epirubicin and cyclophosphamide (FEC) as first-line chemotherapy for metastatic breast cancer. A total of 142 patients (intent-to-treat (ITT)) with at least one measurable lesion were randomised to receive docetaxel 75 mg m(-2) plus epirubicin 75 mg m(-2) or 5-fluorouracil 500 mg m(-2) plus epirubicin 75 mg m(-2) and cyclophosphamide 500 mg m(-2) intravenously once every 3 weeks for up to eight cycles. Prophylactic granulocyte-colony-stimulating factor was only permitted after the first cycle, if required. Per-protocol analysis (n=132) gave an overall response rate for ET of 63.1% (95% confidence interval (CI), 50-78%) and for FEC 34.3% (95% CI, 23-47%) after a median seven and six cycles, respectively. Intent-to-treat population (n=142) gave an overall response rate for ET of 59% (95% CI, 47-70%) and for FEC 32% (95% CI, 21-43%) after a median seven and six cycles, respectively. The median response duration for ET was 8.6 months (95% CI, 7.2-9.6 months) and for FEC 7.8 months (95% CI, 6.5-10.4 months). The median time to progression (ITT) for ET was 7.8 months (95% CI, 5.8-9.6 months) and for FEC 5.9 months (95% CI, 4.6-7.8 months). After a median follow-up of 23.8 months, median survival (ITT) for ET and FEC were 34 and 28 months, respectively. Nonhaematologic grade 3-4 toxicities were infrequent in both arms. Haematologic toxicity was more common with ET and febrile neutropenia was reported in 13 patients (18.6%) in the ET group. Two deaths in the ET group were possibly related to study treatment. In conclusion, both ET and FEC were associated with acceptable toxicity. ET is a highly active first-line therapy for metastatic breast cancer.

A prospective randomized multicentre phase III trial of fotemustine plus whole brain irradiation versus fotemustine alone in cerebral metastases of malignant melanoma.

The main objective of this prospective multicentre randomized phase III study was to compare a combined regimen of fotemustine plus whole brain irradiation with fotemustine alone in terms of cerebral response and time to cerebral progression in patients with melanoma cerebral metastases. Seventy-six patients were randomized to receive either fotemustine (arm A, n = 39) or fotemustine plus whole brain irradiation (arm B, n = 37). Fotemustine was administered intravenously at 100 mg/m(2) on days 1, 8 and 15, followed by a 5 week rest period, then every 3 weeks in non-progressive patients. In arm B, concomitant whole brain irradiation was performed at a total dose of 37.5 Gy (2.5 Gy/day on days 1-5 for three consecutive weeks). Although patients who received fotemustine alone had worse prognostic factors, there was no significant difference in cerebral response (arm A, 7.4%, arm B, 10.0%) or control rates (objective responses plus stable disease) after 7 weeks (arm A, 30%; arm B, 47%) or in overall survival (arm A, 86 days; arm B, 105 days). However, there was a significant difference in favour of arm B for the time to cerebral progression (P = 0.028, Wilcoxon test). In conclusion, fotemustine plus whole brain irradiation delayed the time to cerebral progression of melanoma cerebral metastases compared with fotemustine alone but without a significant improvement in terms of objective control or overall survival.

[Advanced breast cancer: an evaluation of the cost of recurrence]. / Cancer du sein au stade avancé: évaluation du coût de la récidive.

In the context of a medicoeconomic study of the adjuvant treatment of breast cancer, we evaluated the cost of the recurrence. This cost was assessed from the medical records of 146 patients having presented either distant metastases, or a local recurrence followed or not by metastases between 1983 and 1990. We checked according to published data that the frequency of the metastatic risk is negligible if beyond 5 years after the local recurrence. Costs are expressed in 1995 French Francs (FF), with the French Social Security point of view. From the medical records, we calculated the mean cost of each type of recurrence using medical costs (visits, drugs and treatments, assessments, tests, hospital care, outpatient services.) and non medical costs (patient transportation). The costs are 175,168 FF (standard deviation or SD: 127,972) for metastatic recurrence, and respectively 287,582 FF (SD: 142,280) and 115,705 FF (SD: 78,677) for local recurrence followed or not by metastases. There is a significant difference between these figures (p < 0.001). The hospitalization costs are around 66% of the total cost of each type of recurrences and they are significantly higher (p < 0.005) when metastatic disease occurs after a local recurrence. The mean cost of isolated local recurrence added to metastatic recurrence, 290,873 FF, is not different from that of local recurrence followed by metastases, 287,582 FF (p = 0.15). These results will be integrated in a model in order to evaluate the long-term economic consequences of an adjuvant strategy in the treatment of breast cancer and presented in other publications.

[Granisetron (per os) compared with ondansetron (per os) in the prevention of nausea and vomiting induced by mildly emetogenic chemotherapies. Groupe de Recherches en Cancerologie du Nord]. / Granisétron (per os) comparé à ondansétron (per os) dans la prévention des nausées et vomissements induits par des chimiothérapies moyennement émétisantes. Groupe de recherche en cancérologie du Nord.

It is a randomised cross-over multicenter study comparing the efficacy and the tolerance of granisetron (Gra) 1 mg and ondansetron (Ond) 8 mg, oral, given during two consecutive cycles to 188 naive patients scheduled to receive a moderately emetogenic chemotherapy. The antiemetic treatment is given one day per course, 1 hour before chemotherapy and the second administration from 8 to 12 hours after the beginning, during each of the two cycles; alternatively according to the randomisation. Five criteria are assessed; nausea (ordinal and visual analogic scales), emeric episodes (vomiting orland retching), complete response (minor or no nausea, no emetic episode and no rescue treatment), patient preference and tolerance. The intent to treat analysis showed no significant difference at cycle 1 between Gra and Ond; at cycle 2, there is no significant difference in the number of emetic episodes; for the prevention of nausea, the ordinal scale shows a significant difference (p = 0.028 in favour of Gra at day 1 (D1) but not from D2 to D5. Gra induced more complete response than Ond at D1 (p = 0.028), but not from D2 to D5. The cross-over study did not show any period or order effect, whereas a treatment effect on Ond was significant in favour of Gra (p = 0.01). There is no significant patients preference in favour of Gra or Ond. In conclusion, Gra was more efficient in preventing nausea and obtaining complete response on the first day of treatment, significantly at the second cycle. Both Gra and Ond had a good antiemetic activity for moderately emetogenic chemotherapy with complete response rates always over 50% on day 1; delayed emesis remain less weli controlled.

[Adjuvant treatment of cancer of the breast: cost assessment of the protocol used]. / Traitement adjuvant du cancer du sein: évaluation du coût de la stratégie mise en oeuvre.

In this study a cost analysis of therapeutics used in the adjuvant treatment of breast cancer has been performed. Four strategies were considered: chemotherapy (FEC, 6 courses), hormone therapy (tamoxifen, 20 mg/day during 3 years), the association of chemotherapy and hormone therapy, or standard follow-up with neither chemotherapy nor hormone therapy. The costs of these strategies were analysed according to the payer's perspective (social security system). In order to complete the economic data, specific investigations were performed at the Centre Oscar-Lambret (COL), a Cancer Center located in Lille (France). The study shows a high cost for chemotherapy (63,767 FF at 5 years) and a high cost for the association (68,891 FF), in comparison to the cost of hormone therapy alone (45,540 FF) or to the follow-up without adjuvant therapy (38,416 FF). These costs could be confronted to the efficacy data of these different strategies and to the cost of avoided relapses. Cost-effectiveness and cost-benefit ratios of these adjuvant strategies could then be assessed.

[Medico-economical assessment in cancerology]. / Evaluation médico-économique en cancérologie.

In recent studies, the economic criteria has begun to be integrated to the appraisal in cancerology. The question asked by the economist can be framed as follows: what incremental cost should the collectivity or the health insurance system consent, in order to improve the care of cancer patients? This involves first that the cost of the strategies, foreseen or already implemented, can be appraised, then, that indicators can be defined to capture health improvement, and finally, that this health improvement can be quantified. In this article, we present the process of integrated appraisal (cost/result approach). We specifically analyze costs in cancerology, their source and their evolution. We demonstrate the meaning of the integration of economic costs and medical results. We emphasize on the fact that part of the costs, especially those supported by the patient and his close relations, are most of the time excluded from the analysis. Two main points should be carefully analyzed, when proceeding to an appraisal in cancerology: the measurement of the patient's QoL, which represents an expression of the results of the strategy of care; the financing modalities, for the same type of care, if we consider the specificity of the structures involved and the organization of the care. We conclude by mentioning how difficult this task is and under which conditions it should be developed.

Effectiveness of cold cap in the prevention of docetaxel-induced alopecia.

Docetaxel is a new taxoid antineoplastic agent with clinical efficacy especially in breast cancer. One of the most distressing side-effects induced by docetaxel is alopecia. We studied the prevention of alopecia by using a cold cap in 98 patients receiving 100 mg/m2 docetaxel by 1 h i.v. infusion every 3 weeks. One patient was lost to follow-up. 83 patients (86%) were evaluated as a success to the cold cap, as they presented WHO grade alopecia < or = 2 and no need to wear a wig. 14 patients (14%) had to wear a wig; among them; 7 patients withdrew before the evaluation at three cycles. The cold cap is a very effective technique with minimal side-effects for docetaxel-treated patients.