Weight-Based Chemotherapy Dosing May Improve Outcomes in Obese Populations With CRC

Obese patients with colorectal cancer (CRC) were found to experience poor survival from adjuvant chemotherapy that had been dose-reduced, as well as from the average cumulative relative dose (ACRD), according to findings from the OCTOPUS Consortium of trial data that were presented at the 2021 World Congress on Gastrointestinal Cancer.¹

Therefore, the investigators suggested in a presentation during the European Society for Medical Oncology (ESMO) 2021 World Congress on Gastrointestinal Cancer that ACRD is more important than average relative dose intensity (ARDI) for determining patient survival.

“Adjuvant chemotherapy is dosed according to a person’s body surface area, which is calculated from their height and weight. But in obese patients (with a high body mass index [BMI], and who are more likely to have high BSAs [body surface areas]), 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,” reported lead study author Corinna Slawinski, a clinical research fellow in the Division of Cancer Sciences, University of Manchester, United Kingdom, prior to the presentation.

Previous reports have shown that obese patients with CRC have worse outcomes, but this study suggests that these prior findings may be limited or due to other factors, including treatment.

Recently, the American Society of Clinical Oncology (ASCO) updated its guidelines on the treatment of obese patients with cancer to recommend full, weight-based doses of chemotherapy. Findings from the consortium support these guidelines.

“Our study has demonstrated an association between increasing body mass index and modest reductions in the cumulative relative dose of adjuvant chemotherapy in patients with colorectal cancer. And we also saw an association between increased cumulative relative dose and improved survival,” Slawinski said.

The OCTOPUS Consortium included patient-level data including 7269 eligible patients from several large, randomized studies of adjuvant chemotherapy use for CRC (MOSAIC, NCT00275210; SCOT, ISRCTN59757862; PROCTOR-SCRIPT, ISRCTN36266738; and CHRONICLE, NCT00427713). The investigators analyzed BMI and BSA related to chemotherapy doses in patients receiving treatment after undergoing curative surgery.

The primary outcome measure was disease-free survival (DFS), with secondary measures of overall survival (OS) and cancer-specific survival (CSS).

BMI increments of 5 kg/m2 were associated with a 2.04% lower dose of chemotherapy in cycle 1 (95% CI, –2.45 to –1.64; P < .001) as well as a modest lowering of both ACRD (–1.05%; 95% CI, –1.84% to –0.26%; P = .009) and ARDI (–1.02%; 95% CI, –1.43% to –0.62%; P < .001). As such, a patient with a BMI of 37.5 kg/m2 would have a 3% reduction in ACRD and ARDI compared with a patient with a BMI of 22.5 kg/m2.

Five percent increments in ACRD were associated with an improvement in DFS (HR, 0.953; 95% CI, 0.926-0.980; P = .001), OS (HR, 0.931; 95% CI, 0.908-0.955; P < .001), and CSS (HR, 0.941; 95% CI, 0.924- 0.959; P < .001).

Elizabeth Smyth, MD, a consultant in gastrointestinal oncology at Addenbrooke’s Hospital in Cambridge, United Kingdom, and member of the ESMO Faculty for Gastrointestinal Tumours, commented on the results of the study: “Dose reductions for high BMI may be associated with lower cure rates in resected colon cancer treated with adjuvant chemotherapy. 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.”

“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,” Smyth added. “Dosing chemotherapy is complex and includes not only weight but fitness, comorbidities including renal function, and dihydropyrimidine dehydrogenase testing results.”

The study authors noted that further prospective studies are needed before treatment practices can be changed.

“We should take all aspects of the patient into account when making chemotherapy dosing decisions. Dose reductions do seem to be associated with [worse] survival in this study, but these may still be required for safety,” Smyth urged.

References

1. Slawinski C, Malcomson L, Barriuso J, et al. Average cumulative relative dose (ACRD) of adjuvant chemotherapy is more important than average relative dose intensity (ARDI) for colorectal cancer survival, with implications for treating obese patients: the OCTOPUS consortium. Ann Oncol. 2021;32(suppl 3):O-4.
2. Griggs JJ, Bohlke K, Balaban EP, et al. Appropriate systemic therapy dosing for obese adult patients with cancer: ASCO guideline update. J Clin Oncol. 2021;39(18):2037-2048. doi:10.1200/JCO.21.00471