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Preclinical, epidemiological, and small clinical studies suggest that green tea extract (GTE) and its major active component epigallocatechingallate (EGCG) exhibit antineoplastic effects in the colorectum.A randomized, double-blind trial of GTE standardized to 150 mg of EGCG b.i.d. vs placebo over 3 years was conducted to prevent colorectal adenomas (n = 1,001 with colon adenomas enrolled, 40 German centers). Randomization (1:1, n = 879) was performed after a 4-week run-in with GTE for safety assessment. The primary end point was the presence of adenoma/colorectal cancer at the follow-up colonoscopy 3 years after randomization.The safety profile of GTE was favorable with no major differences in adverse events between the 2 well-balanced groups. Adenoma rate in the modified intention-to-treat set (all randomized participants [intention-to-treat population] and a follow-up colonoscopy 26-44 months after randomization; n = 632) was 55.7% in the placebo and 51.1% in the GTE groups. This 4.6% difference was not statistically significant (adjusted relative risk 0.905; P = 0.1613). The respective figures for the per-protocol population were 54.3% (151/278) in the placebo group and 48.3% (129/267) in the GTE group, indicating a slightly lower adenoma rate in the GTE group, which was not significant (adjusted relative risk 0.883; P = 0.1169).GTE was well tolerated, but there was no statistically significant difference in the adenoma rate between the GTE and the placebo groups in the whole study population.

1551 Background: Prevention of colorectal adenomas (CA) can reduce colorectal cancers (CRC). Epidemiological and experimental data suggest that the green tea catechin epigallocatechingallate has an antineoplastic effect in the large bowel. MIRACLE is the largest trial so far to examine the effect of three-year daily intake of green tea extract (GTE) on the incidence of metachronous CA in a Caucasian population. Methods: Prospective, parallel group, double-blinded, placebo-controlled, randomized multicenter trial (40 German centers, recruitment 11/2011-6/2015). Patients (n = 1001, age 50-80y), polypectomy ≤ 6 months and tolerating GTE well (one-month run-in) were randomized to receive decaffeinated GTE standardized to EGCG (150 mg bid, capsules) or placebo (P) for 3 years. Primary endpoint: Incidence of metachronous CA at the 3-year follow-up colonoscopy. Secondary endpoints: Occurrence, number, localization, size, histological subtype of CA, frequency of CRC, biomarker and safety. Strata: study center, low-dose aspirin (≤100 mg/d). Results: Clinical parameters were well balanced. CA incidence at the 3-year follow-up colonoscopy was analyzed in the modified ITT set (modITT; n = 309 patients (GTE), n = 323 (placebo), timely follow up colonoscopy) and the per protocol set (PP, modITT set without major protocol violations). Incidence of CA was 55.7 % (P) and 51.1% (GTE), (modITT, adj. RR 0.905, one sided, p = 0.081), respectively 54.3 % (P) and 48.3% (GTE) (PP, adj. RR 0.883, one sided, p = 0.058). These differences did not reach statistical significance. In the preplanned exploratory analysis regarding gender incidence of CA in females was 47.9% (P) and 47.6% (GTE) in the modITT-set (adj. RR 0.989; 95%-CI: 0.753,1.299; p = 0.935), respectively 45.4% (P) and 46.9% (GTE) in the PP-set (adj. RR 1.014; 95%-CI: 0.748, 1.373; p = 0.930). In contrast, in the male population incidence of CA in the follow-up colonoscopy was 60.4% (P) and 52.9% (GTE) in the modITT-set (adj. RR 0.846; 95% CI 0.717, 0.999); p = 0.048), respectively 59.1% (P) and 49.1% (GTE) in the PP-set (RR 0.803, 95% CI: 0.666, 0.969; p = 0.022). Thus, GTE intake was associated with a significant, 12.4 relative and 7.5% absolute reduction of metachronous CA in the male modITT population. There were no differences with respect to safety between the groups. Conclusions: GTE reduced the incidence of metachronous CA. However, a significant effect was only observed in the in the male population whereas there was no effect in the female population. Clinical trial information: NCT 01360320.

High-dose methotrexate (HDMTX) is a component of many cancer treatment regimens. Despite careful management, delayed renal clearance, followed by extremely high serum levels with potentially life-threatening toxicity can occur. In the present study, we report our results of carboxypeptidase-G2 (CPDG2) rescue in 8 patients with delayed methotrexate elimination and renal impairment after HDMTX therapy for lymphoma or osteosarcoma. A dose of 50 U/kg CPDG2 was administered. MTX plasma levels decreased rapidly and recovery of renal function was observed in all patients. No patient developed severe WHO grade 4 MTX toxicity. CPDG2 provides an alternative route of MTX elimination by converting it to inactive and non-toxic metabolites. CPDG2 rescue was well tolerated, safe and very effective in preventing severe or life-threatening MTX toxicity.

Fallbeschreibungen: Es wird uber vier Patienten berichtet, die zur Abklarung erhohter Transaminasen unter dem Verdacht auf akute Hepatitis stationar eingewiesen wurden. Nach Ausschluss einer spezifischen und unspezifischen Virushepatitis, einer Autoimmunhepatitis, einer leberschadigenden Stoffwechselerkrankung und einer extrahepatischen Cholestase wurde eine toxische Leberschadigung klinisch und histologisch gesichert. Da bei den Patienten andere medikamentose Noxen und besonders Alkohol als Ursache der Schadigung auszuschliesen waren, musste die Lebertoxizitat auf die Einnahme von Statinen bezogen werden. Klinischer Verlauf: Nach Absetzen des Cholesterinsynthesehemmers und unter Fortfuhrung der ubrigen hausarztlichen Medikation normalisierten sich die Transaminasen innerhalb von Wochen. Eine Reexposition wurde aus ethischen Grunden nicht durchgefuhrt. Schlussfolgerung: Bei der Verordnung eines HMG-CoA-Reduktase-Hemmers muss auf eine mogliche Leberschadigung hingewiesen und eine regelmasige Kontrolle der Transaminasen durchgefuhrt werden.

We conducted a randomised phase II study to compare irinotecan monotherapy with irinotecan in combination with infusional 5-fluorouracil/folinic acid (5-FU/FA) regarding efficacy and safety of these regimens in second-line therapy after failed fluoropyrimidine therapy in patients with metastatic colorectal cancer (mCRC). Patients and Methods: 55 patients with mCRC after failure of a first-line therapy were randomised to receive either irinotecan 80 mg/m2 followed by FA 500 mg/m2 and 5-FU 2,000 mg/m2 24 h weekly for 6 weeks, with courses repeated on day 50 (arm A), or irinotecan 125 mg/m2 weekly for 4 weeks, with cycles repeated on day 43 (Arm B). Results: Both regimens yielded a partial response rate of 11% with identical progression-free survival (3.7 months for both regimens) and similar overall survival (9.5 months for the combination therapy vs. 10.7 months for the monotherapy). Both regimens were very well tolerated, and the combination of irinotecan with 5-FU/FA did not result in increased toxicity. Conclusion: Our study confirms that irinotecan alone or in combination with infusional 5-FU/FA is an effective and safe regimen for CRC patients who failed first-line therapies. However, the role of 5-FU in addition to irinotecan for fluoropyrimidine failures remains unclear. Due to the small sample size, a decision cannot be made which therapy should be preferred, and a significant contribution to the efficacy of single-agent irinotecan is not obvious from this small randomised phase II trial.