Thanks, Mike for the educating comments, but also for the link to the NCBI article. I found it particularly interesting because of the explanation of the internal workings of Capecitabine and $-FU, and the reports on other side effects besides neuropathy. Non-US clubbers should also be aware that some of the conclusions are less valid for patients in other geographic regions of the world:
The ideal dosing of capecitabine is controversial as regional differences have been seen in the tolerance of oral fluoropyrimidines [ . . . ]those enrolled in trials in the United States had higher rates of grade 3 and 4 adverse events (relative risk [RR], 1.77), an increase in the frequency of dose reduction (RR, 1.72), and higher rates of treatment discontinuation (RR, 1.83). The results [ . . ] in the adjuvant setting also showed increased grade 3 and 4 adverse events (RR, 1.47) and higher rates of discontinuation (RR, 2.09). On further analysis, East Asian patients fared the best overall.
and
A number of possible explanations for the variation in side effect profiles between countries have been proposed. Folic acid supplementation is much more widespread in the United States than in Europe which might account for a portion of the differences. Pharmacogenetics may also play a role as genetic differences between Caucasian and Japanese patients have been discovered, but this is unlikely to explain the variation in events between the United States and European populations who have similar genetic profiles.
Besides the difference in the dosing for the US, there appear to be cost benefits for the use of Capecitabine compared to 5-FU, although these do not always reflect in the out-of-pocket costs for the patient:
In a 2009 article by Chu et al [ . . .] the mean predicted monthly complication cost was 136% greater with 5-FU monotherapy when compared to capecitabine. This equated to an additional US$601/month (95% CI: $469–$737) spent treating complications associated with 5-FU. When each agent was given in combination with oxaliplatin, this value increased to US$1165/month (95% CI: $892–$1595).
[ . . . ]
the X-ACT trial (capecitabine versus 5-FU in the adjuvant treatment of CRC) showed the cost of treating patients with capecitabine in the United Kingdom was 57% lower than that for 5-FU.61 Capecitabine use led to decreased hospitalization rates and cost savings of £3653. Societal costs for such things as patient travel and time off work were also lowered by £1318, again reinforcing the potential cost benefit of capecitabine.
[ . . . ]
trials NO16966 and NO16967 was also reported in 2009.62 In the analysis, the authors found the incremental improvement in quality-adjusted progression free survival days (QAPFSD) favored XELOX over FOLFOX4 in both first- and second-line settings. Specifically, patients gained 10.5 QAPFSD from first-line and 11.3 QAPFSD from second-line treatment. Cost calculations found savings for the National Health Service of £7600 and £3900 for patients treated with XELOX in first- and second-line settings, respectively.
[ . . . ]
a study published in the United States demonstrated a lower cost with capecitabine monotherapy when compared to 5-FU and leucovorin of US$6683 versus US$9304.63 It showed a higher acquisition cost for capecitabine but lower administration and complication costs. This held true when oxaliplatin was added to the regimens with costs of US$11,463 and US$14,320.
[ . . . ]
Overall, these studies demonstrate a measurable cost saving when using capecitabine in place of 5-FU.
However, costs to the patient do not always reflect this:
Reimbursement policies vary internationally and even regionally within the United States. Multiple analyses have shown cost savings when capecitabine is compared to 5-FU, but variability in insurance coverage for oral cytotoxics can lead to significantly higher out-of-pocket expenses for patients, especially since 5-FU is usually fully covered by insurance plans.
As said, interesting read. Thanks again,
Greetings, L