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Abstract
BackgroundIt is unclear whether the UGT1A1 status, single heterozygous (SH) or wild type (WT), is associated with the efficacy and toxicity of irinotecan monotherapy in advanced gastric cancer (AGC). We investigated the association between clinical outcomes (efficacy and safety) and UGT1A1 status in patients who received irinotecan monotherapy.MethodsWe evaluated AGC patients who received irinotecan monotherapy between January 2011 and December 2017. Efficacy was assessed according to overall survival (OS) and progression-free survival (PFS). Toxicity was graded using the Common Toxicity Criteria for Adverse Events (version 4.0).ResultsA total of 100 patients were evaluated (62 and 38 patients with UGT1A1 WT and SH, respectively). In the WT and SH groups, the irinotecan dose was reduced in 19 (30.6%) and 18 (47.2%) patients (p = 0.135), respectively; treatment was delayed due to adverse events (AEs) in 19 (30.6%) and 13 (34.2%) patients (p = 0.826), respectively; the median PFS was 3.15 and 3.25 months (HR, 0.734; 95% CI 0.465–1.158; p = 0.184), respectively; and the median OS was 10.4 and 7.26 months (HR, 1.137; 95% CI 0.752–1.721; p = 0.543), respectively. Severe hematological AEs (Grade ≥ 3) were significantly more frequent in the SH group than in the WT group (63% vs. 36%; p = 0.008), while severe non-hematological AEs was not significantly different (16.0% vs. 6.5%; p = 0.173).ConclusionThere was no significant difference in the efficacy of irinotecan monotherapy between UGT1A1 WT and UGT1A1 SH, but UGT1A1 SH was associated with a high frequency of severe hematological toxicity.
Highlights
Gastric cancer is the third leading cause of cancer-related mortality worldwide, accounting for 8.8% of all cancer deaths [1]
Of the 174 patients initially assessed, 74 patients were excluded because the irinotecan dose was initially reduced (n = 50), they did not undergo UGT1A1 tests (n = 19), or they had a UGT1A1 double-heterozygous or homozygous status (n = 5; Fig. 1)
The common (5% or higher) severe adverse events (AEs) were decreased white blood cell count (11% and 16%), neutropenia (15% and 32%), anemia (21% and 24%), and anorexia (1.6% and 11%) in the UGT1A1 wild type (WT) and UGT1A1 single heterozygous (SH) groups. This multicenter retrospective study showed that among advanced gastric cancer (AGC) patients treated with irinotecan monotherapy as second- or later-line treatment the incidence of hematological AEs was higher in UGT1A1 SH patients than UGT1A1 WT patients
Summary
Gastric cancer is the third leading cause of cancer-related mortality worldwide, accounting for 8.8% of all cancer deaths [1]. Advanced gastric cancer (AGC) is primarily treated with systemic chemotherapy, with fluoropyrimidine and platinum-based combination therapy recommended by several guidelines [2, 3] as first-line chemotherapy. The Pan-Asian-adapted ESMO Clinical Practice Guidelines recommend second-line chemotherapy with either irinotecan, taxanes, ramucirumab monotherapy, or combination ramucirumab and paclitaxel therapy for metastatic gastric cancer [7]. The latest Japanese gastric cancer treatment guideline (5th edition) recommends irinotecan monotherapy as a third-line chemotherapy [3]. It is unclear whether the UGT1A1 status, single heterozygous (SH) or wild type (WT), is associated with the efficacy and toxicity of irinotecan monotherapy in advanced gastric cancer (AGC). Conclusion There was no significant difference in the efficacy of irinotecan monotherapy between UGT1A1 WT and UGT1A1 SH, but UGT1A1 SH was associated with a high frequency of severe hematological toxicity
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