Breast cancer

Why we need to talk more about chemotherapy toxicity and dose adjustment

Patients receiving adjuvant chemotherapy will need more dose adjustments to avoid toxicity than those recommended in protocols based on unrealistic clinical trials, a review shows.

In real world practice many chemotherapy patients are having higher rates of treatment-related toxicity than the carefully selected and monitored participants in clinical trials, according to a review of evidence by Dr Thiru Prasanna and colleagues at the Chris O’ Brien Lifehouse and Royal Prince Alfred Hospital, Sydney.

Writing in the Asia Pacific Journal of Clinical Oncology , they say patients having adjuvant, risk-reducing chemotherapy for lower risk cancers may be exposed to unnecessarily toxic and lethal adverse effects because the reference clinical trials for treatment protocols were for curative intent and involved very select patient populations unrepresentative of the age, body weight and ethnicity of real world patients.

In a review of 28 curative-intent chemotherapy trials used as the basis for government-backed eviQ protocols, they found significant levels of treatment toxicity that required doses to be reduced, delayed or missed.

Protocol completion rates were less than 90% for non-breast cancer trials and dose modifications were required in up to 40% of participants, mostly due to haematological toxicity. And while treatment related deaths were infrequent, some reference trials showed rates of 0.5-2%.

“Thus even in  ideal, clinical trial settings chemotherapy dose calculation remains imprecise and subject to adjustment as clinical appropriate,” they said.

And in clinical practice, higher rates of dose modification will be needed to deal with factors such as  obese or underweight patients and old age, particularly as elderly patients were under-represented in clinical trials. Ethnicity was also key concern in dose calculation, with febrile neutropenia rates as high as 50% in Asian patients receiving chemo doses based on trials done in Caucasian patients.

The review authors also noted that the nuances of chemotherapy dosing adjustment had been lost in media discussion around under-dosing, particularly in adjuvant settings.

“Anecdotally, many oncologists now face resistance from patients to recommended chemotherapy dose modifications despite significant toxicity,” they said.

Appropriate dose modifications remained the standard of care but would need careful and clear discussion with the patient to be agreed on and documented, they concluded.

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