More Proof That Less Chemo Is Best in the Elderly

Hello. I'm David Kerr, professor of cancer medicine at the University of Oxford. I'd like to discuss the results of a recent analysis in one of my favorite journals, Annals of Oncology.

In a publication led by Dr Hofheinz, the German Rectal Cancer Study Group gives an interesting insight as to the age-related benefits and dis-benefits of adjuvant chemotherapy [in locally advanced rectal cancer].^[1] There is a degree of controversy as to whether it's useful to add oxaliplatin to preoperative chemoradiotherapy or postoperative adjuvant regimes in rectal cancer. The German group had previously shown in a large, well-conducted randomized trial of approximately 1200 patients that the addition of oxaliplatin seemed to improve disease-free survival.^[2]

In this post hoc retrospective analysis, they wanted to look at the impact of age. The entering ages are the continuous variable in the statistical model. They looked at patients under 60 years, ages 60 to 70, and age 70 and above.

In a nutshell, they showed that the important benefits of the addition of oxaliplatin to conventional fluoropyrimidine chemoradiotherapy is confined to those who are under 70. There are no benefits at all that they could demonstrate in those age 70 and above.

This is part of a trend that we are starting to recognize. In our earlier QUASAR studies, our adjuvant trials of fluoropyrimidines in colorectal cancer, we noted early on that the benefits of chemotherapy became much less marked when we treated progressively older patients, particularly 70 and above.^[3]

We have the results from de Gramont and other colleagues looking at MOSAIC,^[4] and other studies looking at the use of adjuvant oxaliplatin in colon cancer, again suggesting that the benefits to the patient group over 70 are definitely and somewhat limited.

It's an interesting question to pose, isn't it, that there seems to be something about elderly patients that confers a degree of "resistance" to the addition of drugs like oxaliplatin.

It's not really to do with a lack of tolerance [or] increased side effects, and therefore more dose reductions and so on. That does not seem to be the case when we and others have looked back at the relative dose delivered, dose intensity, and so on.

The pharmacology of the drug, the delivery of it, seems somewhat similar. Is it possible that there may be some pharmacokinetic alterations that means that an adequate quantum of drug is not reaching its target site? Microscopic metastatic disease, possibly? Could there be some subtle variations in access to DNA binding patterns? That seems less likely.

Is it anything that we know that defines different molecular biology of old cancers compared with young cancers? Not really.

We know that older patients with older tumors tend to have a higher mutational burden. This is something that may be relevant when choosing patients for immunotherapy studies and so on, but there is nothing that really jumps out of the page in terms of looking at conventional molecular markers that would allow us to completely separate young from old.

It's something of a mystery, something to be solved, I think.

The practical clinical take-home message for us is that when we are delivering adjuvant therapy to patients age 70 and above with rectal or colon cancer, single-agent fluoropyrimidine seems like an entirely reasonable treatment plan to offer the patient and decide with us whether they feel the benefits are worth potential dis-benefits of hassle, side effects, and so on.

This isn't ageism. This isn't some nonspecific, non–evidence-based discrimination against the elderly. It’s not withholding drugs. In fact, there is a growing evidence base that at least in the adjuvant setting for colorectal cancer, less may be as good as more in terms of the drug combinations that we offer.

I'd be really interested in any ideas that you have of your own and anything that you would like to discuss. I'd be happy to engage with that.

Thanks for listening, as always. For the time being, Medscapers, over and out. Thank you.

Any views expressed above are the author's own and do not necessarily reflect the views of WebMD or Medscape.

Cite this: David J. Kerr. More Proof That Less Chemo Is Best in Elderly Colorectal Cancer Patients - Medscape - Jan 24, 2019.

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