Chemo dose may affect survival in obese CRC patients

Obese patients with colorectal cancer (CRC) may be receiving lower cumulative doses of chemotherapy than non-obese patients which may impact their survival outcomes, according to results of a study from the OCTOPUS consortium.

“Our study has demonstrated an association between increasing body mass index (BMI) and modest reductions in the cumulative relative dose of adjuvant chemotherapy in patients with CRC,” said lead author Dr Corinna Slawinski from the University of Manchester, Manchester, UK, at ESMO GI 2021.

“[W]e also saw an association between increased cumulative relative dose and improved survival. This supports the recently published ASCO guidance that full, weight-based chemotherapy doses should be used to treat obese adult patients,” she added. [J Clin Oncol 2021;39:2037-2048]

The population comprised 7,269 patients enrolled in the randomized MOSAIC, SCOT, PROCTORSCRIPT, or CHRONICLE (CRC-ACT) trials who were receiving adjuvant chemotherapy following curative surgery for CRC and who had data on BMI, body surface area (BSA), and chemotherapy dose. Percentages of actual-to-expected (BSA-based) dose intensity (cumulative dose/treatment duration in weeks) and cumulative dose over the whole chemotherapy course were used to determine average relative dose intensity (ARDI) and average cumulative relative dose (ACRD), respectively.

Every 5 kg/m² increase in BMI was associated with a 2.04 percent reduction in chemotherapy dose in cycle 1 of treatment, as well as 1 percent reductions in ACRD and ARDI. [ESMO GI 2021, abstract O-4]

After adjusting for age, sex, performance status, t-stage, n-stage, and BMI, 5 percent increases in ACRD were associated with significant improvements in disease-free survival (DFS; hazard ratio [HR], 0.953, 95 percent confidence interval [CI], 0.926–0.980; p=0.001), overall survival (OS; HR, 0.931, 95 percent CI, 0.908–0.955; p<0.001), and cancer-specific survival (CSS; HR, 0.941, 95 percent CI, 0.924–0.959; p<0.001).

Conversely, there was no association between ARDI and survival outcomes (DFS: HR, 1.015, 95 percent CI, 0.967–1.065; p=0.552; OS: HR, 1.035, 95 percent CI, 0.990–1.081; p=0.134; CSS: HR, 1.022, 95 percent CI, 0.982–1.064; p=0.282).

Previous studies have suggested that obese patients have poorer survival outcomes than non-obese patients following curative surgery for CRC. However, it was unknown if the poorer outcomes were due to BMI itself or other factors such as treatment dose.

“Adjuvant chemotherapy is dosed according to a person’s BSA,” said Slawinski. “[I]n obese patients (with a high BMI, and who are more likely to have high BSAs), doses are often capped, or based on an idealized weight, because of concern that large doses might increase side effects. This means that obese patients may receive proportionately lower doses of chemotherapy,” she said.

“These indirect effects through suboptimal treatment might explain poorer survival in obese patients, rather than direct effects of obesity resulting from, for example, tumour biology,” she continued.

While these results suggest that obese patients should be given the full dose of chemotherapy based on body weight, toxicities still need to be considered.

“Toxicity has the potential to reduce quality of life and can be life threatening. [T]here may also be other reasons for reducing chemotherapy doses, such as comorbidities, so it is important that dosing and treatment decisions are individualized to the patient,” said Slawinsky.

“Adjuvant chemotherapy has the potential to cure patients with residual micrometastatic disease following curative surgery, so it is important that we maximize the benefits for all patients,” pointed out Dr Elizabeth Smyth from Addenbrooke’s Hospital, Cambridge, UK, and member of the ESMO Faculty for gastrointestinal tumours, who was not affiliated with the study.

“The main message from this study is that we should consider whether dose reductions are necessary in patients with a high BMI when treating them with adjuvant chemotherapy,” she said. However, dosing is dependent on more than just weight and includes other factors such as fitness and comorbidities, she added. 

“We should take all aspects of the patient into account when making chemotherapy dosing decisions. Dose reductions do seem to be associated with [poorer] survival in this study, but these may still be required for safety,” she concluded, highlighting that more research is warranted before practice changing decisions are made.