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Purpose. To evaluate progression-free survival (PFS), overall response rate (ORR) and disease control rate (DCR) as potential surrogate endpoints (SEP) for overall survival (OS) in second-line treatment for metastatic colorectal cancer (mCRC). Methods. A systematic literature search of randomised trials of second-line chemotherapy for mCRC reported from January 2000 to July 2013 was performed. Correlation coefficients weighted by number of patients in the treatment arms between median PFS, ORR and DCR with median OS were estimated. Results. Twenty-three trials reflecting 10 800 patients met the inclusion criteria. Median PFS and OS across all trials were 4.5 months and 11.5 months and median ORR and DCR were 11.4% and 65%, respectively. PFS showed moderate correlation with OS [RPFS = 0.73; 95% confidence interval (CI) 0.61-0.82]. In contrast, ORR only weakly correlated with OS (RORR = 0.58; 95% CI 0.38-0.72, n = 22). Despite a small number of studies (n = 10) reporting on DCR, moderate correlation with OS was observed (RDCR = 0.74; 95% CI 0.56-0.86). Conclusion. Based on the available trial-level data, PFS may serve as an appropriate SEP in second-line chemotherapy for mCRC. A small number of studies revealed moderate correlation of DCR with OS that justifies further investigation. [ABSTRACT FROM AUTHOR]

Purpose. This study investigated the impact of early tumor shrinkage (ETS) on progression-free- (PFS) and overall survival (OS) in patients with metastatic colorectal cancer (mCRC) treated within the AIO KRK 0104 trial as first-line therapy. Moreover, correlations of ETS with clinical characteristics and prognostic markers were evaluated. Patients and methods. In total, 121 patients were included into this analysis. Patients were treated with cetuximab combined with either CAPIRI or CAPOX. ETS at six weeks was defined as a relative change of ≥ 20% in the sum of the longest diameters of target lesions compared to baseline. Survival times were compared between patients with ETS ≥ 20% versus no-ETS. Results. ETS ≥ 20% was observed in 59% of all patients with KRAS wild-type tumors. In these patients ETS ≥ 20% was associated with higher overall response rate (82% vs. 19%, p < 0.001). Also, PFS (8.9 vs. 4.7 months, p < 0.001) and OS (31.6 vs. 15.8 months, p = 0.005) were significantly superior in ETS ≥ 20% of patients compared to no-ETS. In patients with KRAS mutant mCRC ETS ≥ 20% neither had an effect on PFS nor OS. Cetuximab-induced skin toxicity correlated with the occurrence of ETS ≥ 20% (p = 0.002). Conclusion. In patients with KRAS wild-type tumors treated with cetuximab plus capecitabine-based chemotherapy ETS ≥ 20% is an important predictor of favorable outcome. [ABSTRACT FROM AUTHOR]

Background: The objective of this retrospective study was to assess the survival of patients after resection of hepatic and pulmonary colorectal metastases to identify predictors of long-term survival. Methods: Patients receiving chemotherapy alone were compared to patients receiving surgery and chemotherapy in a matched-pair analysis with the following criteria: UICC stage, grading, and date of initial primary tumor occurrence. Results: A total of 30 patients with liver and lung metastases of colorectal carcinoma underwent resection. In 20 cases, complete resection was achieved (median survival, 67 months). Incomplete resection and preoperatively elevated carcinoembryonic antigen (CEA) levels are independent risk factors for reduced survival. Patients developing pulmonary metastases prior to hepatic metastases had the worst prognosis. Surgical resection significantly increased survival compared to chemotherapy alone in matched-pair analysis (65 vs. 30 months, p = 0.03). Conclusions: Incomplete resection and elevated CEA levels are predictors of poor outcome. Matched-paired analysis confirmed that surgical resection in combination with chemotherapy appears to be superior to chemotherapy alone. [ABSTRACT FROM AUTHOR]

Purpose: To determine whether irinotecan plus oxaliplatin (mIROX) is superior to irinotecan plus infusional 5-fluorouracil, leucovorin (FUFIRI) as first-line therapy of patients with metastatic colorectal cancer (mCRC). Patients and methods: A phase III, randomised, open-label multicentre study compared standard treatment with FUFIRI (irinotecan 80mg/m2, 5-fluorouracil 2000mg/m2, folinic acid 500mg/m2 weekly times 6) to mIROX using an identical schedule of irinotecan plus oxaliplatin 85mg/m2 applied on days 1, 15 and 29 of a 7-week cycle. The primary end-point was progression-free survival (PFS). Results: A total of 479 eligible patients were randomly assigned. Progression-free survival was 7.2months in the mIROX arm and 8.2months in the FUFIRI arm [hazard ratio=1.14; 95% confidence interval (CI) 0.94–1.37; P =0.178]. Comparable results were also obtained for overall survival time with 19months in the mIROX-arm and 22months in the FUFIRI-arm (hazard ratio=1.08, P =0.276). Both regimens induced an identical objective response rate (ORR) of 41%, but disease control rate (ORR plus stable disease) was significantly greater in the FUFIRI group (81% versus 68%, P =0.001). Most frequent grades 1–4 side-effects of mIROX and FUFIRI treatment were nausea (80% versus 73%) and delayed diarrhoea (79% versus 68%). Grades 3–4 toxicities were generally below 10%, except for diarrhoea which was more frequent in the mIROX-arm compared to the FUFIRI-arm (19% versus 30%, P =0.006) Conclusion: mIROX failed to show superior activity compared to high-dose 5-FU/folinic acid plus irinotecan. Due to better tolerability the combination of high-dose 5-FU/folinic acid and irinotecan remains a standard of care in first-line treatment of metastatic colorectal cancer. [Copyright &y& Elsevier]