Objective TAS‐102 is effective for treating patients with metastatic colorectal cancer (mCRC). This study determined whether combining bevacizumab (Bmab) with TAS‐102 improves clinical outcomes in refractory mCRC. Patients and Methods We retrospectively analyzed data from Japanese patients with refractory mCRC who received TAS‐102 (35 mg/m2, twice a day) with (T‐B group) or without Bmab (TAS‐102 monotherapy; T group) between July 2014 and December 2018. The primary endpoint was median overall survival (OS), and secondary endpoints were median time to treatment failure, overall response rate, and the incidence of adverse events. Clinical outcomes were compared using propensity score matched analysis. Results Data from 57 patients were analyzed (T‐B group: 21 patients, T group: 36 patients). Median OS was significantly longer in the T‐B group than the T group (14.4 months vs. 4.5 months, p < .001). Cox proportional hazard analysis showed that combination therapy with Bmab was significantly correlated with OS. Propensity score matched analysis confirmed that the median OS was significantly longer in the T‐B group than the T group (14.4 months vs. 6.1 months, p = .006) and that there was a significant correlation between Bmab and OS. The incidence of hypertension (grade ≥2) as an adverse event was significantly higher in the T‐B group than the T group (23.8% vs. 0.0%, p = .005), whereas other adverse events were comparable between the two groups. Conclusion Treatment with Bmab in combination with TAS‐102 is significantly associated with improved clinical outcomes in patients with mCRC refractory to standard therapies. Implications for Practice Combining bevacizumab (Bmab) with TAS‐102 significantly improved overall survival and several prognostic indicators in patients with metastatic colorectal cancer (mCRC) refractory to standard therapies, with manageable toxicities. Treatment with Bmab in combination with TAS‐102 is significantly associated with improved clinical outcomes in patients with mCRC.
Purpose Irinotecan is effective for metastatic colorectal cancer (mCRC). SN-38 is an active metabolite of irinotecan, which is formed by carboxylesterase and inactivated by UDP-glucuronyltransferase (UGT) 1A1. The UGT enzyme activity is reduced in patients with homozygous mutation in UGT1A1 genes (*6/*6, *28/*28 and *6/*28); thus dose reduction is required for prevention of severe adverse events associated with irinotecan. The present study was designed to investigate the relationship between UGT1A1 polymorphisms and the incidence of adverse events or the therapeutic effect in mCRC patients who received irinotecan. Methods Sixty-three mCRC patients who received irinotecan during January 2014 and May 2018 were the subjects of this study. The incidence of adverse events, including diarrhea and neutropenia, and the therapeutic effect of irinotecan were compared among homozygous group, heterozygous group and wild-type group. The initial dose of irinotecan was 150 mg/m 2 in the heterozygous group and wild-type group, while the dose was reduced by 20% (120 mg/m 2 ) in the homozygous group. Results The UGT1A1 polymorphisms occurred in 15.9%, 33.3%, and 50.8% for homozygous group, heterozygous group, and wild-type group, respectively. The average dose of irinotecan during overall cycles was not significantly different among three groups, despite the reduction of initial dose in homozygous group. There were no significant differences in the incidence rates of adverse events, tumor response, or time to treatment failure among three groups. Conclusion The present study demonstrated that dose reduction by 20% ensured safety and efficacy of irinotecan in mCRC patients with homozygous mutation in UGT1A1 genes.
While modified FOLFIRINOX therapy is effective for treating advanced pancreatic cancer, it frequently causes severe neutropenia. The present study investigated the effect of severe neutropenia on clinical outcomes in advanced pancreatic cancer patients who received modified FOLFIRINOX. The study subjects were 51 patients (30 males and 21 females) with advanced pancreatic cancer who received modified FOLFIRINOX (2h bolus injection of oxaliplatin at 85 mg/m2, 2 h bolus injection of L-leucovorin at 200 mg/m2, 90min bolus injection of irinotecan at 150 mg/m2, followed by continuous infusion of 5-fluorouracil for 46 h at 2400 mg/m2 without bolus 5-fluorouracil) during the period from January 2014 to May 2018. No patients had prior history of chemotherapy. Adverse events, including neutropenia, were graded according to the Common Terminology Criteria for Adverse Events, version 4.0. Median overall survival (OS) was the primary endpoint, while median time to treatment failure (TTF), overall response rate (ORR), and the incidence of other adverse events were secondary endpoints. Severe neutropenia (grade ≥3) occurred in 39 patients (76.4%), and Cox proportional hazard analysis identified high total bilirubin level as a significant risk factor. Median duration of OS was significantly longer in patients with severe neutropenia than in those without it (21.3 months versus 8.9 months, p = 0.020). Moreover, there was a significant correlation between OS and the grade of neutropenia (r = 0.306, p = 0.029). ORR tended to be higher, though not significantly, in patients with severe neutropenia. In contrast, the incidence rates of other adverse events were not different between the two groups. Severe neutropenia is an independent predictor of prognosis in advanced pancreatic cancer patients received modified FOLFIRINOX therapy.
Background/Aim: To clarify whether renal dysfunction affects the incidence of adverse events associated with oxaliplatin, the present study was designed to investigate the relationship between creatinine clearance (Ccr) and the incidence of oxaliplatin-related adverse events. Patients and Methods: A total of 287 CRC patients who received the first cycle of oxaliplatin-based chemotherapy were eligible. Adverse events, including nausea, vomiting, neutropenia and thrombocytopenia, were graded, and the relationship between Ccr and the incidence of adverse events was examined using multivariable logistic regression analysis. Results: A multivariable analysis indicated that the incidence of grade ≥2 nausea increased, while the incidence of other adverse events tended to be higher, as the Ccr decreased. Particularly, renal dysfunction (Ccr <60 ml/min) was a significant risk factor for grade ≥2 nausea (p=0.042). Conclusion: Care should be taken to avoid adverse events associated with oxaliplatin in patients with renal dysfunction.
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