Robert W. Dubois

Comparison of pegfilgrastim with filgrastim on febrile neutropenia, grade IV neutropenia and bone pain: a meta-analysis of randomized controlled trials

ABSTRACT Background and objective: While head-to-head clinical trials demonstrate pegfilgrastim to be as efficacious as filgrastim in reducing chemotherapy-induced neutropenia, these studies lacked the statistical power to demonstrate better outcomes with one therapy compared to the other. Our objective was to obtain a pooled estimate of the effect of pegfilgrastim compared with filgrastim on incidence of febrile neutropenia (FN), and related outcomes among patients with solid tumors and malignant lymphomas receiving myelosuppressive chemotherapy. Research design and methods: We searched PubMed and EMBASE for articles published from January 1, 1990 to August 31, 2006 reporting on randomized controlled trials (RCTs) that compared the efficacy and safety of pegfilgrastim versus filgrastim. We only accepted studies in which filgrastim (5 µg/kg/day) and pegfilgrastim (100 µg/kg or a fixed dose of 6 mg) were administered at approved doses indicated on the package insert. Pooled relative risk (RR) was estimated using the conservative random effects, empirical Bayesian method of Hedges and Olkin. Main outcome measures: Rates of grade IV neutropenia and of FN, time to absolute neutrophil count (ANC) recovery, and bone pain. Results: We identified five RCTs, with a total of 617 patients, evaluating the efficacy of a single dose of pegfilgrastim per cycle versus daily filgrastim injections. Although only one study had a statistically significant difference in FN reductions favoring pegfilgrastim over filgrastim (relative risk reduction of 50%; p = 0.027), the pooled RR showed a statistically significant favorable result for pegfilgrastim (RR = 0.64; 95% CI, 0.43–0.97). Grade IV neutropenia rates (for cycle 1: RR = 0.99; 95% CI, 0.91–1.08; cycle 2: RR = 0.88; 95% CI, 0.70–1.11; cycle 3: RR = 0.80; 95% CI, 0.47–1.36; cycle 4: RR = 0.90; 95% CI, 0.71–1.13), time to ANC (SMD = 0.11, 95% CI, –0.34–0.56), and incidence of bone pain (RR = 0.95; 95% CI, 0.76–1.19) were similar between the two G‑CSFs. The included trials varied in the type of cancer, chemotherapy regimen and type of trial. Conclusion: A single dose of pegfilgrastim performed better than a median of 10–14 days of filgrastim in reducing FN rates for patients undergoing myelosuppressive chemotherapy.

Treatment of patients with metastatic renal cell cancer: a RAND Appropriateness Panel.

New developments in the treatment of patients with metastatic renal cell cancer (MRCC) have suggested a need to reevaluate the role of systemic therapies. The authors convened a panel of medical and urologic oncologists to rate the appropriateness of the main options.

Cost-effectiveness of pegfilgrastim versus 6-day filgrastim primary prophylaxis in patients with non-Hodgkin's lymphoma receiving CHOP-21 in United States

ABSTRACT Objectives: Prophylaxis with granulocyte-colony stimulating factor (G-CSF) reduces the risk of febrile neutropenia (FN) in patients receiving myelosuppressive chemotherapy. Randomized clinical trials have shown that pegfilgrastim, a 2nd-generation G-CSF, is at least as effective as the 1st-generation G-CSF filgrastim. In the meta-analysis of trials pegfilgrastim performed better than filgrastim with respect to FN risk. The incremental cost-effectiveness of primary prophylaxis (starting in cycle 1 and continuing in subsequent cycles of chemotherapy) with pegfilgrastim versus filgrastim used for 6 days (as is often used in clinical practice) was estimated in patients with aggressive non-Hodgkins lymphoma (NHL) receiving myelosuppressive chemotherapy in the United States. Methods: A decision-analytic model was constructed from a health insurers perspective with a life-time study horizon. The model considered direct medical costs and outcomes related to reduced FN and potential survival benefits due to reduced FN-related mortality. Inputs for the model were obtained from the medical literature. Sensitivity analyses were conducted across plausible ranges in parameter values. Results: The incremental cost-effectiveness (ICER) of pegfilgrastim versus 6-day filgrastim primary prophylaxis was

Impact of systemic lupus erythematosus on health, family, and work: the patient perspective.

2167/FN episode avoided. Adding survival benefit from avoiding FN mortality yielded an ICER of

Cost-effectiveness of primary versus secondary prophylaxis with pegfilgrastim in women with early-stage breast cancer receiving chemotherapy.

5532/LY gained or

Cost-Effectiveness of Pegfilgrastim Versus Filgrastim Primary Prophylaxis in Women With Early-Stage Breast Cancer Receiving Chemotherapy in the United States

6190/QALY gained. When the potential benefit of optimized chemotherapy was included, the ICER was

Risk of Upper Gastrointestinal Injury and Events in Patients Treated With Cyclooxygenase (COX)-1/COX-2 Nonsteroidal Antiinflammatory Drugs (NSAIDs), COX-2 Selective NSAIDs, and Gastroprotective Cotherapy An Appraisal of the Literature

1494/LY gained or

Impact of Systemic Hypertension on the Cardiovascular Benefits of Statin Therapy—A Meta-Analysis

1677/QALY gained. The most influential factors included cost of pegfilgrastim, relative risk of FN between pegfilgrastim and filgrastim, FN case-fatality rate, cost of filgrastim and baseline FN risk. Conclusions: Pegfilgrastim is cost-effective in primary prophylaxis of FN compared to 6 days per cycle of filgrastim, in patients with NHL receiving myelosuppressive chemotherapy (e.g., cyclophosphamide + doxorubicin + vincristine + prednisolone [CHOP-21]) chemotherapy. Study limitations included lack of direct evidence linking G-CSF use with a reduction in FN-related mortality and limited data that show a relationship between relative dose intensity (RDI) and cancer-specific patient survival.

Development and validation of a case ascertainment tool for ankylosing spondylitis.

Qualitative research among patients with systemic lupus erythematosus (SLE) can identify aspects of the disease relevant to clinical research and practice. A phenomenological, mixed‐method approach was used to investigate these disease‐driven health issues.

Principles for planning and conducting comparative effectiveness research.

OBJECTIVE Prophylaxis with granulocyte colony-stimulating factor (G-CSF) reduces the risk of febrile neutropenia (FN) in patients receiving myelosuppressive chemotherapy. We estimated the incremental cost-effectiveness of G-CSF pegfilgrastim primary (starting in cycle 1 and continuing in subsequent cycles of chemotherapy) versus secondary (only after an FN event) prophylaxis in women with early-stage breast cancer receiving myelosuppressive chemotherapy with a >or=20% FN risk. METHODS A decision-analytic model was constructed from a health insurers perspective with a lifetime study horizon. The model considers direct medical costs and outcomes related to reduced FN and potential survival benefits because of reduced FN-related mortality. Inputs for the model were obtained from the medical literature. Sensitivity analyses were conducted across plausible ranges in parameter values. RESULTS The incremental cost-effectiveness ratio (ICER) of pegfilgrastim as primary versus secondary prophylaxis was