A study small of with 48 patients with locally advanced rectal cancer receiving neoadjuvant chemotherapy from the University of Colorado Cancer Center found that patients receiving lower-than-recommended doses saw their tumours shrink more than patients receiving the full dose. The was study presented at the 2020 Gastrointestinal Cancers Symposium.
Chemotherapy used to shrink a tumour before surgery, called neoadjuvant chemotherapy, is becoming more common in many cancers, including stage II and III rectal cancer. However, the chemotherapy regimens FOLFOX and CapeOx used in this setting come with significant side effects, to the degree that many patients are unable to complete the recommended schedule.
"I think we need bigger studies to explore less intensive therapy - maybe lower doses, maybe a shorter course of treatment - to see what is the optimal dosing prior to surgery," said Dr Ashley E Glode, PharmD, assistant professor at the Skaggs School of Pharmacy and Pharmaceutical Sciences, and the study's first author.
In some cancers, a tumour may be entwined with nearby organs and blood vessels to the point that surgery is not initially an option. Most patients with locally advanced rectal cancer are surgical candidates, but chemotherapy used to shrink a tumour prior to surgery has been associated with more successful surgeries and a lower rate of cancer recurrence.
As a high-volume centre for the treatment of these cancers, University of Colorado Cancer Center oncologists, including Dr Christopher Lieu, noticed that patients who were unable to complete the recommended course of neoadjuvant chemotherapy seemed to have similar or even better outcomes than patients receiving the full dose, prompting the current study.
"We do all sorts of supportive care options to help keep patients on these therapies at the recommended, high doses,” said Lieu, who is CU Cancer Center's interim associate director for clinical research. “But based on our observations and on this early study, we're starting to talk about having less hesitancy to drop the drug or at least decrease the dosing."
Of the 48 patients included in the study, only 12.5 percent were able to tolerate the full dose of chemotherapy. Due to side effects, none of the six patients taking the regimen CapeOx completed the recommended dose.
"CapeOx is a treatment option mostly taken at home as a pill so it's easier for patient - they only have to come in for infusion once every three weeks,” added Glode. “But the regimen wasn't tolerated by any patients on this study. It makes us think about not offering the option of CapeOx, and sticking with FOLFOX instead.”
In 42 patients receiving less than the full dose of FOLFOX, 45 percent experienced a complete response, meaning that cancer was undetectable after treatment (negating the need for surgery in eight cases). In six patients receiving the full dose of FOLFOX, 33 percent experienced a complete response.
"This is a small, single-institution study, but it certainly gives us pause," he concluded. "Why would patients take more chemotherapy and have more side effects, when less chemotherapy seems equally or even more beneficial?"