No abstract

Background: Since 2000, the combination of three drugs and targeted drugs has further improved the survival of metastatic colorectal carcinoma(mCRC), while the incidence of side effects of triple regimens over grade 3 are much higher than double regimens. Since adjusting the dosage of drugs can't avoid serious toxicity, here we present a new methode of optimizing the scheme by adjusting the time and mode of administration.Methods: TROT is a prospective, open-label, multicentric phase II randomized trial in which unresectable and previously untreated mCRC patients are randomized to receive first-line XELOX followed by XELIRI after disease progression AE bevacizumab(arm A) or these two schemes alternatively use AE bevacizumab of every 2 cycles until disease progression(arm B). The primary endpoint is to compare the efficacy of these two treatment strategies in terms of time to failure of strategy (TFS) and secondary objectives were ORR、DCR、OS and safety. The curative effect will evaluate in every 2 cycles.Results: 66 patients were enrolled.6 patients were lost to follow or fall off. The analysis of curative effect has been evaluated in 31 patients in the arm A and 29 patients in the arm B.ORR was 27.6% in the first-line and 11.5% in the second-line in the arm A vs 67.7% in the arm B (P < 0.001).The DCR was 89.7% in the first-line and 57.7% in the second-line in the arm A vs 100% in the in the arm B (P < 0.001). ETS was 64.5% and DpR was 46% in the arm B. Median TFS was 12.9 months in arm A vs 12.0 months in arm B (P ¼0.735,HR 1.103). Median OS was 20.4 months in arm A vs 18.8 months in arm B (P¼0.712,HR 0.887).Grade !3 AEs occurred in 10 patients (32%)in arm B vs 21 patients (72.4%)in arm A(P<0.001). No treatment-related death was reported. There were significantly lower AEs than current triplet regimens.Conclusions: XELOX/XELIRI alternate regimen AE bevacizumab,compared with first-line XELOX followed by XELIRI after disease progression AE bevacizumab,can improve the effect of tumour shrinkage and significantly reduce treatment-related side effects in mCRC patients with widespread metastasis,and this alternate regimen may become an alternative for patients who can't tolerate the three-drug combination regimen.

Background Hydrocortisone premedication reduces the risk of antibodies to Infliximab (ATIs) formation in patients receiving Infliximab (IFX) therapy for inflammatory bowel disease (IBD). Aim To determine the safety of hydrocortisone premedication withdrawal in IBD patients with sustained clinical response on maintenance therapy with IFX. Methods We performed an observational prospective pharmacoclinical study in a tertiary referral centre including all consecutive IBD outpatients with no previous IFX infusion reaction, and in clinical remission on maintenance IFX (alone or in combination therapy) for at least 6 months. This cohort was followed for one year after discontinuation of hydrocortisone premedication. Results Among the 268 IBD outpatients, 95 patients met the inclusion criteria (mean age 38 years; 64% male; 80% Crohn’s disease, 45% combination therapy). The median IFX duration was 5 years (0.54-14) with a mean infused dose of 533 mg (200-1000) and a mean interval duration of 7.9 weeks (4-10). None of the patients developed permanent ATIs or infusion-related reaction at 1 year. Four patients developed transient ATIs without loss of clinical response. There was no significant variation of Infliximab serum through levels (5.5 µg/mL vs 5.9 µg/mL) measured at the time of the 3 IFX infusions before and after hydrocortisone withdrawal. Loss of response rate to IFX was 18% at one year. Conclusion Hydrocortisone discontinuation is safe in IBD patients with sustained clinical remission on maintenance therapy with IFX. Our data suggest that routine premedication with hydrocortisone is unnecessary in patients in prolonged remission under IFX maintenance therapy.