FOLFIRI and regorafenib combination therapy with dose escalation of irinotecan as fourth-line treatment for patients with metastatic colon cancer according to UGT1A1 genotyping

Abstract

Here we report a case of metastatic colon cancer treated with 5-fluorouracil, leucovorin, and escalated doses of irinotecan (FOLFIRI) combined with regorafenib in the fourth-line setting after uridine diphosphate glucuronosyltransferase (UGT)1A1 genotyping analysis. A 66-year-old male was initially diagnosed with Union Internationale Contre le Cancer stage III descending colon cancer and underwent curative surgery. He received postoperative adjuvant chemotherapy; however, liver metastasis developed and a partial hepatectomy was performed thereafter. Unfortunately, pulmonary metastases and recurrent liver tumors were found despite a series of systemic treatments with multiple combinations of cytotoxic and biologic agents. Recently, a novel multikinase inhibitor, regorafenib, was approved for the treatment of metastatic colorectal cancer refractory to other therapeutic modalities. As further treatment, we combined regorafenib with FOLFIRI, which included dose escalations of irinotecan, after UGT1A1 genotyping analysis. The therapeutic results were promising, with the improvement in liver and pulmonary metastases being classified as stable disease and partial response, respectively. Moreover, the progression-free survival was over 6 months. FOLFIRI, with dose escalation of irinotecan according to UGT1A1 genotyping plus regorafenib appears to be a promising salvage therapy for patients with refractory metastatic colorectal cancer.

Regorafenib Plus FOLFIRI With Irinotecan Dose Escalated According to Uridine Diphosphate Glucuronosyltransferase 1A1 Genotyping in Patients With Metastatic Colorectal Cancer

“…However, clinical presentations are variable, and patients with UGT1A1*1/*28 can typically tolerate the recommended initial irinotecan dose of 180 mg/m 2( 16 ) . By contrast, patients homozygous for UGT1A1*1/*1 tolerate higher doses of irinotecan owing to an active UGT1A1; in accordance with this observation, we observed that such patients can tolerate an irinotecan dose as high as 290 mg/m 2( 14 ) . For safety reasons, in the aforementioned study, we administered an initial dose of 180 mg/m 2 , subsequently increasing it by 30 mg/m 2 every two cycles and observing for the development of any grade ≥3 AEs or SAEs, reverting to the previously tolerated dosage upon observation of any grade ≥3 AEs or SAEs.…”

“…Therefore, the irinotecan dose should be adjusted according to UGT1A1 genotyping for obtaining minimal AEs and optimal oncological results. Recently, we successfully treated a case of mCRC with escalated irinotecan doses (FOLFIRI regimen) combined with regorafenib in the fourth-line treatment after UGT1A1 genotyping 14 . Herein we report an analysis in which regorafenib combined with FOLFIRI adjusted according to UGT1A1 genotyping was used for treating previously treated patients with mCRC.…”

Oncologic Outcomes in Metastatic Colorectal Cancer with Regorafenib with FOLFIRI as a Third- or Fourth-Line Setting

“…On the contrary, clinical presentations in patients with UGT1A1 *1/*28 vary individually, but these patients generally tolerate the recommended initial irinotecan dose of 180 mg/m 2 [34]. However, patients with the homozygous UGT1A1 *1/*1 genotype are more resistant to irinotecan-associated AEs and could tolerate an irinotecan dose as high as 260 mg/m 2 in previous observational studies [12], [35]. As the result, for patient safety and treatment efficacy of irinotecan dose-escalated FOLFIRI, UGT1A1 genotyping was carried out before treatment was initiated.…”

Combination chemotherapy with Regorafenib in metastatic colorectal cancer treatment: A single center, retrospective study

“…Regorafenib combination use was reported by Wang et al[ 28 ]. Regorafenib combined with FOLFIRI was used in a metastatic colorectal cancer patient in fourth line therapy after FOLFIRI, FOLFOX, cetuximab, and bevacizumab were used.…”