Oral capecitabine (Xeloda s ) is an effective drug with favourable safety in adjuvant and metastatic colorectal cancer. Oxaliplatinbased therapy is becoming standard for Dukes' C colon cancer in patients suitable for combination therapy, but is not yet approved by the UK National Institute for Health and Clinical Excellence (NICE) in the adjuvant setting. Adjuvant capecitabine is at least as effective as 5-fluorouracil/leucovorin (5-FU/LV), with significant superiority in relapse-free survival and a trend towards improved disease-free and overall survival. We assessed the cost-effectiveness of adjuvant capecitabine from payer (UK National Health Service (NHS)) and societal perspectives. We used clinical trial data and published sources to estimate incremental direct and societal costs and gains in quality-adjusted life months (QALMs). Acquisition costs were higher for capecitabine than 5-FU/LV, but higher 5-FU/LV administration costs resulted in 57% lower chemotherapy costs for capecitabine. Capecitabine vs 5-FU/LV-associated adverse events required fewer medications and hospitalisations (cost savings d3653). Societal costs, including patient travel/time costs, were reduced by 475% with capecitabine vs 5-FU/LV (cost savings d1318), with lifetime gain in QALMs of 9 months. Medical resource utilisation is significantly decreased with capecitabine vs 5-FU/LV, with cost savings to the NHS and society. Capecitabine is also projected to increase life expectancy vs 5-FU/LV. Cost savings and better outcomes make capecitabine a preferred adjuvant therapy for Dukes' C colon cancer. This pharmacoeconomic analysis strongly supports replacing 5-FU/LV with capecitabine in the adjuvant treatment of colon cancer in the UK.
The gemcitabine-based treatments had comparable activity and tolerability. Similar survival characteristics and different toxicity profiles suggested that gemcitabine-platinum may be evaluated further in patients after anthracycline failure.
In western countries breast cancer is still the leading cause of death of women. Very promising results have been obtained by combining vinorelbine and doxorubicin, two of the most active drugs in metastatic breast cancer. However, despite the activity reported, this combination has shown a 10% rate of grade 2-4 cardiac toxicity, mainly due to the total cumulative doses of anthracycline delivered. The aim of this study was to divide the total dose of doxorubicin into two administrations on days 1 and 8, in order to cut down its toxicity while maintaining the same activity. Fifty-two chemotherapy naïve patients with metastatic breast cancer entered into the study and were treated with vinorelbine 25 mg/m2 plus doxorubicin 25 mg/m2 both on days 1 and 8 every three weeks. Fifty-one patients were eligible and evaluable for toxicity while 47 of them were evaluable for activity. Haematological toxicity was predominantly related to neutropenia, with grade 3/4 in 16% of cycles. Non-haematological toxicity was represented by alopecia grade 3 (which affected 65% of the patients), local phlebitis and severe constipation. No clinically significant cases of neuropathy or cardiac dysfunction were seen. With regard to activity, 38 out of 47 patients (80%) responded to therapy, nine of them achieving complete responses (19%). Median response duration was 16 months and the median overall survival was 22.7 months. We conclude that the fractionated administration of vinorelbine and doxorubicin is associated with excellent haematological and non-haematological tolerability (especially as regards cardiac toxicity), coupled with high levels of activity comparable to those observed using regimens based on unfractionated administration of treatment.
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