Wethe shape and scale of the Weibull log hazard custom peptide synthesis curves between treatments. Overlap of credible intervals should not be used when interpreting significance of results as the credible intervals may not be comparable due to differing variances.22 The projected mean duration of PFS may provide clinicians more confidence when selecting the initial therapeutic strategy for treatment naïve CLL patients. PFS and overall survival outcomes may be affected by patient and disease characteristics including: age, gender, stage of disease, doubling lymphocyte count time, patient performance status, comorbidities, immunophenotype, cytogenetic abnormalities, rhein genetic over expression of the heavy chain immunoglobulin protein, and blood cell counts.23 Overall, the patients included in our comparison network appeared to be fairly homogenous and had more favorable prognostic characteristics. The trials included in our meta analysis enrolled a relatively small number of patients with high risk features, including those with 17p and 11q deletions and some trials did not report cytogenetic profiles. Therefore, our results apply to younger, healthier patients with low to intermediate risk CLL, and additional studies are necessary in order to define the optimal initial treatment strategy for high risk patients.
In the published literature, we identified a review of a mixed treatment comparison that evaluated therapies for previously untreated CLL. The MTC was conducted to support a European marketing authorization application for rituximab. As described in a health technology assessment review of the submission, nattokinase the MTC included FCR, FC, chlorambucil, fludarabine, alemtuzumab, and bendamustine.24 Unlike our study, which compared differences between shape and scale parameters of PFS curves, the MTC described in the HTA review used a Cox regression model for the PFS outcome which assumes proportional hazards. Given the various prognostic factors for CLL, a proportional hazards assumption may be challenged. Despite the differences in study design, both studies estimated that FCR had better treatment effect on disease progression than chlorambucil. The MTC described in the HTA review is not published so we cannot determine anastrozole how the rest of our results compared. The RCT conducted by Hillmen, et al.13 demonstrated that alemtuzumab had significantly improved PFS when compared against chlorambucil.
However, our results suggested that alemtuzumabhad the highest hazard of disease progression or death among the comparators and is not a satisfactory first line therapy option for younger, healthier patients with low to intermediate risk disease. It is uncertain if the hazard rate for alemtuzumab was associated with lower therapeutic activity, higher mortality risk from adverse events, or unobserved differences in base line patient characteristics. Given the activity of alemtuzumab in CLL patients with poor prognosis or higher risk disease, the clinical value of alemtuzumab appears to be in its use as second line or salvage therapy. Combination regimens such as FCR are generally associated with greater toxicities than monotherapy. Even though our results showed that FCR had the greatest potential of preventing disease progression, fludarabine and chlorambucil monothera.