ABSTRACT
BACKGROUND: Chemotherapy plus bevacizumab is a standard option for first-line treatment in metastatic colorectal cancer (mCRC) patients. We assessed whether no continuation is non-inferior to continuation of bevacizumab after completing first-line chemotherapy. PATIENTS AND METHODS: In an open-label, phase III multicentre trial, patients with mCRC without disease progression after 4-6 months of standard first-line chemotherapy plus bevacizumab were randomly assigned to continuing bevacizumab at a standard dose or no treatment. CT scans were done every 6 weeks until disease progression. The primary end point was time to progression (TTP). A non-inferiority limit for hazard ratio (HR) of 0.727 was chosen to detect a difference in TTP of 6 weeks or less, with a one-sided significance level of 10% and a statistical power of 85%. RESULTS: The intention-to-treat population comprised 262 patients: median follow-up was 36.7 months. The median TTP was 4.1 [95% confidence interval (CI) 3.1-5.4] months for bevacizumab continuation versus 2.9 (95% CI 2.8-3.8) months for no continuation; HR 0.74 (95% CI 0.58-0.96). Non-inferiority could not be demonstrated. The median overall survival was 25.4 months for bevacizumab continuation versus 23.8 months (HR 0.83; 95% CI 0.63-1.1; P = 0.2) for no continuation. Severe adverse events were uncommon in the bevacizumab continuation arm. Costs for bevacizumab continuation were estimated to be â¼30,000 USD per patient. CONCLUSIONS: Non-inferiority could not be demonstrated for treatment holidays versus continuing bevacizumab monotheray, after 4-6 months of standard first-line chemotherapy plus bevacizumab. Based on no impact on overall survival and increased treatment costs, bevacizumab as a single agent is of no meaningful therapeutic value. More efficient treatment approaches are needed to maintain control of stabilized disease following induction therapy. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, number NCT00544700.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Colorectal Neoplasms/drug therapy , Liver Neoplasms/drug therapy , Adult , Aged , Aged, 80 and over , Bevacizumab/administration & dosage , Camptothecin/administration & dosage , Camptothecin/analogs & derivatives , Colorectal Neoplasms/mortality , Colorectal Neoplasms/pathology , Female , Fluorouracil/administration & dosage , Follow-Up Studies , Humans , Irinotecan , Leucovorin/administration & dosage , Liver Neoplasms/mortality , Liver Neoplasms/secondary , Male , Middle Aged , Neoplasm Staging , Organoplatinum Compounds/administration & dosage , Oxaliplatin , Prognosis , Prospective Studies , Survival Rate , Young AdultABSTRACT
Analysis of the observations of several Pluto-Charon occultation and transit events in 1985 and 1986 has provided a more detailed knowledge of the system. The sum of the radii of Pluto and Charon is 1786 +/- 19 kilometers, but the individual radii are somewhat more poorly determined; Pluto is 1145 +/- 46 kilometers in radius and Charon is 642 +/- 34 kilometers in radius. The mean density of the system is 1.84 +/- 0.19 grams per cubic centimeter, implying that more than half of the mass is due to rock. Charon appears to have hemispheres of two different colors, the Plutofacing side being neutral in color and the opposite hemisphere being a reddish color similar to Pluto.
