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docetaxel chemotherapy drug may be less effective in females with obesity

Tue, 07/07/2020 - 15:06
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Breast cancer patients who are overweight or have obesity might benefit less from treatment with docetaxel, a common chemotherapy drug, than lean patients, according to an international team of researchers who carried out a retrospective analysis of data from a large clinical trial.

"Docetaxel is a lipophilic drug, suggesting that fat present in the body could absorb part of the drug before it can reach the tumour," explained Professor Christine Desmedt from the KU Leuven Laboratory for Translational Breast Cancer Research. "If follow-up research confirms that this finding is solely related to the pharmacological characteristics of docetaxel, this might also apply to patients with other cancer types that are treated with docetaxel, such as prostate or lung cancer. These results also make us wonder whether other chemotherapy drugs from the same family, like paclitaxel, will show the same effect. More research is needed before changes in treatment can be implemented. Patients who have concerns about docetaxel can discuss these with their doctor.”

The findings reported in the paper, ‘Differential Benefit of Adjuvant Docetaxel-Based Chemotherapy in Patients With Early Breast Cancer According to Baseline Body Mass Index’, published in the Journal of Clinical Oncology, highlights a differential response to docetaxel according to BMI, and it calls for a body composition–based re-evaluation of the risk-benefit ratio of the use of taxanes in breast cancer. Although, the results must be confirmed in additional series.

In most European countries, more than 50% of women are overweight or have obesity. In the US, the rate is over 63% of women and this proportion is expected to further increase in the coming years. It is not widely known, but women with obesity have a higher risk of getting breast cancer and breast cancer patients with obesity have a higher risk of relapsing. Moreover, while many cancer patients are overweight or have obesity, the efficacy of anticancer drugs according to their BMI is generally not known.

Lipophilic drugs, such as taxanes, have a high affinity for adipose tissue and a resulting higher volume of distribution. For the study, the researchers re-analysed clinical trial data to investigate whether the efficacy of docetaxel-based chemotherapy differs from non-docetaxel–based chemotherapy in patients with breast cancer according to their baseline BMI.

Using data from the BIG 2-98 trial, comparing non-docetaxel– to docetaxel-containing chemotherapy, a team led by researchers from KU Leuven and the Institut Jules Bordet (Belgium), the University of Milan and National Cancer Institute (Italy) analysed data from a clinical trial with over 2,800 breast cancer patients that started around the turn of the millennium. Patient data were collected over the course of more than ten years.

The researchers then looked at how many patients relapsed and how many had passed away. Their statistical analysis of the data shows that overweight/obesity patients who received docetaxel as part of their treatment had poorer outcomes than lean patients. This difference was not observed in patients who received the chemotherapy regimen that did not include docetaxel.

"In the medical and research world, we need to pay more attention to how obesity affects the biology, progression and treatment efficacy of breast cancer. Much work remains to be done in this field,” said Professor Biganzoli of the Unit of Medical Statistics and the Data Science Research Center, University of Milan and the Italian National Cancer Institute.