Dose Capping May Explain Reduced Survival in Patients With Colorectal Cancer and High BMI

Capping doses of adjuvant chemotherapy may worsen survival outcomes in colorectal cancer (CRC) patients with a high body mass index (BMI), new research suggests.

The research was presented at the European Society for Medical Oncology (ESMO) World Congress on Gastrointestinal Cancer 2021 by Corinna Slawinski, MBBS, of the University of Manchester in the United Kingdom.

Dr Slawinski noted that adjuvant chemotherapy is often capped at a body surface area of 2.2m², potentially reducing the average cumulative relative dose (ACRD) and average relative dose intensity (ARDI) in patients with high BMIs.

To investigate potential links between ACRD, ARDI, BMI, and survival outcomes in patients with CRC, Dr Slawinski and colleagues evaluated data from 4 randomized trials within the OCTOPUS consortium — the MOSAIC trial (ClinicalTrials.gov Identifier: NCT00275210), the SCOT trial (EudraCT Number: 2007-003957-10), the CHRONICLE trial (ClinicalTrials.gov Identifier: NCT00427713), and the PROCTOR-SCRIPT trial (ISRCTN Number: 36266738).

The data encompassed 7271 patients. Both ACRD and ARDI were determined as percentage values of actual versus expected dose, averaged across the number of drugs in the regimen.

The results showed no significant relationship between ARDI and survival, including disease-free survival (hazard ratio [HR], 1.015; 95% CI, 0.967-1.065), overall survival (HR, 1.035; 95% CI, 0.990-1.081), and cancer-specific survival (HR, 1.022; 95% CI, 0.982-1.064).

However, there was a significant relationship between ACRD and survival outcomes. Each 5% ACRD increment increase was linked with:

• A 5% reduction in mortality for disease-free survival (HR, 0.953; 95% CI, 0.926-0.979)
• A 7% reduction in mortality for overall survival (HR, 0.931; 95% CI, 0.908-0.955)
• A 6% reduction in mortality for cancer-specific survival (HR, 0.941; 95% CI, 0.924-0.959).

In addition, each 5 kg/m² increment increase of BMI was associated with reductions in ACRD (-1.048; 95% CI, -1.838 to -0.257) and ARDI (-1.021; 95% CI, -1.427 to -0.615).

“These modest reductions would equate to approximately a 4% to 5% reduction in ARDI and ACRD if we compared a normal BMI to a morbidly obese BMI,” Dr Slawinski said.

“In conclusion, average cumulative dose appeared to be more important than average relative dose intensity in determining survival in colorectal cancers,” she said. “BMI was associated with a modest reduction of both average cumulative relative dose and average relative dose intensity.”

These results suggest that dose capping might explain some of the poorer survival outcomes seen in CRC patients with obesity, but more research is needed, Dr Slawinski said.  

Reference

Slawinski CGV, Malcomson L, Barriuso J, et al. Average cumulative relative dose of adjuvant chemotherapy is more important than average relative dose intensity  for colorectal cancer survival, with implications for treating obese patients: The OCTOPUS consortium. Presented at: ESMO World Congress on Gastrointestinal Cancer; June 30-July 3, 2021. Abstract O-4.

This article originally appeared on Cancer Therapy Advisor