Clinical Brief – July 31st
Using a math model, physicians from the Memorial Sloan Kettering Cancer Center (MSKCC) tried to find a better way to take capecitabine (Xeloda), an often-used chemotherapy drug for breast and bowel cancer. They say that this new dosing regimen may potentially lower the risk of side effects for patients with breast cancer.
Where’s the evidence?
In a review of preclinical and early trial data, researchers found that it’s possible to take capecitabine at a flat dose of 2,000 mg twice daily, in a “7 days on and 7 days off” regimen. In trials using this so called 7-7 regimen, the number of cases of severe diarrhea, nausea, and other gastrointestinal side effects reported was notably lower vs what’s been reported in trials using the standard dose.
Give me a bit more background
Capecitabine is an FDA-approved chemotherapy for metastatic breast and bowel cancers. It’s thought to be a palliative treatment, so having side effects that lower the quality of life would work against the purpose of treatment.
The standard dose is 1,250 mg/m2 twice daily, given in a “14 days on and 7 days off” regimen (aka the 14-7 regimen). In clinical trials, 28-54% of patients on the 14-7 regimen got diarrhea, and 7-19% got severe or life-threatening diarrhea. To get an idea of what severe diarrhea is, think 7 or more stools per day, incontinence, with possible hospitalization. Doesn’t sound very palliative, does it?
No wonder then that some physicians would opt for a lower starting dose in an attempt to mitigate the risk of side effects. However, this puts the efficacy of the treatment in doubt. Sacking efficacy to lower the risk of toxicity doesn’t make much sense either.
So instead of blindly lowering the dose, researchers from the MSKCC modeled the expected effect of capecitabine and found that the anti-cancer effect of capecitabine peaks after about 8 days, which meant that in a 14-day regimen, the second half only contributed to toxicity, not efficacy.
Does it work? A Phase III trial testing the efficacy of the 7-7 regimen vs the conventional dosing is ongoing (NCT02028494). For now, it’s comforting to see that the early trials cited in this review reported that the 7-7 regimen led to progression-free survivals similar to those reported previously for the 14-7 regimen.
For patients with breast cancer, taking capecitabine in a 14-7 regimen may come with some serious gastrointestinal side effects, but arbitrarily reducing the dose may not be the best way out.
This 7-7 regimen for capecitabine is promising, but a review of early trials such as this report isn’t enough evidence to support switching over to the 7-7 regimen en mass. A proper trial is needed to confirm that efficacy isn’t compromised in an attempt to improve its safety profile.