Mitomycin C and capecitabine: An additional option as an advanced line therapy in patients with metastatic colorectal cancer

Abstract

BACKGROUND

In recent years survival of patients with metastatic colorectal cancer (mCRC), though still limited, has improved significantly; clearly, when the disease becomes refractory to standard regimens, additional treatment options are needed. Studies have shown that mitomycin C (MMC), an antitumor antibiotic, and capecitabine, a precursor of 5-fluorouracil, may act synergistically in combination. The efficacy of MMC/capecitabine has been demonstrated in the first-line setting, but only a few small studies have tested it in the advanced-line setting, with contradictory results.

AIM

To summarize our experience using MMC/capecitabine as an advanced line treatment for mCRC.

METHODS

A retrospective study was conducted at a tertiary medical center including all patients with histologically proven mCRC who were treated with MMC/capecitabine after at least two previous lines of standard chemotherapy in 2006-2020. Data on patient demographics and past medical history, laboratory, pathological, and radiological factors, and treatment and survival were collected from the files. Survival analyses were performed using the Kaplan-Meier method. The association of patient and tumor characteristics with treatment effectiveness and toxicity was evaluated with univariate and multivariate proportional hazard Cox regression analyses. P ≤ 0.05 was considered statistically significant.

RESULTS

The cohort consisted of 119 patients of median age 64 years (range 37-85). Patients received a median of 2 MMC/capecitabine cycles (range 0.5-9.0). Thirty-four patients (28.6%) experienced grade ≥ 3 toxicity, including 2 (1.7%) with grade 4; there was no drug-related mortality. The objective response rate was 0.8%, and the disease control rate, 24.4%. Median progression-free survival (PFS) was 2.1 mo (range 0.2-20.3), and median overall survival, 4.8 mo (range 0.2-27.5). The 6-month overall survival rate was 44%; 8.7% of patients remained progression-free. Factors associated with longer PFS were lower gamma-glutamyl transferase level (P = 0.030) and primary tumor location in the left colon (P = 0.017). Factors associated with longer overall survival were lower gamma-glutamyl transferase level (P = 0.022), left-colon tumor location (P = 0.044), low-to-moderate histological grade (P = 0.012), Eastern Cooperative Oncology Group performance status 0-1 (P = 0.036), and normal bilirubin level (P = 0.047).

CONCLUSION

MMC/capecitabine is an active, available, and relatively safe regimen for use beyond standard lines of therapy in mCRC. Several clinical and laboratory parameters can identify patients more likely to benefit.

Keywords: Colorectal cancer; Metastatic cancer; Chemotherapy; Mitomycin C/Capecitabine; Advanced line treatment

Core Tip: Survival with metastatic colorectal cancer has improved significantly. However, when the disease becomes refractory, patients are left with limited options. Mitomycin C (MMC) and capecitabine combination is a potential treatment option for metastatic colorectal cancer (mCRC) patients beyond standard lines of treatment. Only a few small studies have tested it in the advanced-line setting, with contradictory results. We present our experience using the MMC/capecitabine combination. Our findings suggest that MMC/capecitabine is a safe, generally well-tolerated regimen. Ours is the largest series on the use of MMC/capecitabine in refractory mCRC. We were able to identify well-defined subgroups which derived clinical benefit from this combination.