Published online Nov 15, 2023. doi: 10.4251/wjgo.v15.i11.1913
Peer-review started: May 23, 2023
First decision: July 31, 2023
Revised: August 31, 2023
Accepted: October 11, 2023
Article in press: October 11, 2023
Published online: November 15, 2023
Colorectal cancer (CRC) represents one of the most common and lethal solid tumors. When diagnosed in an early stage, surgery +/- adjuvant chemotherapy may result in cure; however, up to half of all patients present or develop metastases during the course of the disease (mCRC). Standard chemotherapy combinations in use for the treatment of metastatic disease include FOLFIRI, FOLFOX, and XELOX, frequently administered with biological agents such as bevacizumab and cetuximab, resulting in an improved outcome. However, once the disease becomes resistant to standard lines, the prognosis is dismal and further treatment options are limited. In the present study we retrospectively examined the effectiveness and tolerability of mitomycin C (MMC)/capecitabine as an advanced line in patients with mCRC who had progressed on standard systemic regimens.
To determine whether the MMC/capecitabine regimen, a potentially synergistic combination, could represent a valid therapeutic option in patients with refractory mCRC. The use of this combination in this setting has not been fully investigated as yet.
Ours is the largest study published so far on the use of MMC/capecitabine as third or further line of treatment in mCRC. We were able to determine the antitumor activity of this regimen as well as the adverse events resulting from its administration.
This was a retrospective analysis which included 119 patients with previously treated mCRC cared for at a single tertiary facility in Israel over a period of 14 years (2006-2020). Data on patient and tumor characteristics at the onset of MMC/capecitabine and prior treatments were retrieved from the patients’ medical records. A detailed analysis on the delivery of MMC/capecitabine including number of cycles, duration of treatment, dose intensity, its efficacy and toxicity, was carried out. Univariate and multivariate analyses on the impact of various patient and tumor characteristics on response and survival outcomes were performed.
All 119 patients were evaluable for efficacy and toxicity. One patient (0.8%) achieved a partial remission and 28 patients (23.5%) had stable disease for a disease control rate of 24.3%. Median duration of disease control, progression-free survival (PFS) and overall survival (OS) were 4.2 mo, 2.1 mo, and 4.8 mo, respectively, with an estimated 6-mo OS rate of 44.0% and of PFS of 8.7%. The disease control rate was higher in patients with metachronous than with synchronous metastatic disease, and in patients with lower pre-treatment GGT levels, normal hemoglobin, and higher serum albumin levels. PFS correlated with left tumor location and lower GGT levels, while OS correlated with those two parameters as well as with histological grade, performance status and normal bilirubin levels.
MMC/capecitabine as an advanced line in patients with mCRC is generally well tolerated and notwithstanding the almost universally lack of objective responses, about one quarter of our patient population achieved disease control. Moreover, the efficacy and safety features of this easily accessible regimen seem comparable to the two approved treatment options in this setting, regorafenib and TAS-102. Importantly, based on simple and readily available clinical and laboratory parameters, we were able to identify subgroups of patients more likely to benefit from the administration of MMC/capecitabine.
Based on our results, we believe that evaluation of MMC/capecitabine as an advanced line in mCRC should be further pursued. At the same time, intensive research should focus on identifying active novel combinations as this remains an unmet need in refractory mCRC.