A Randomized Placebo-Controlled Trial of Bupropion for Cancer-Related Fatigue: Study Design and Procedures

Background: Cancer-related fatigue is a significant problem and is associated with poor quality of life. Behavioral interventions include exercise and cognitive-behavioral therapy, which survivors may be unwilling or unable to adopt. Pharmacologic interventions (e.g., selective serotonin reuptake inhibitors) have been disappointing. One potential therapy is the antidepressant bupropion, a norepinephrine-dopamine reuptake inhibitor that targets both inflammation and the hypothalamic-pituitary-adrenal axis. The current study is intended to provide a rigorous test of the efficacy and tolerability of bupropion for cancer-related fatigue. Methods: A randomized, double-blind, placebo-controlled trial will examine the effects of bupropion on cancer-related fatigue. The trial will be conducted nationwide through the University of Rochester Medical Center (URMC) National Cancer Institute Community Oncology Research Program (NCORP). Disease-free breast cancer survivors (n = 422) who completed chemotherapy and/or radiotherapy 12-60 months previously and report significant fatigue will be randomized 1:1 to receive bupropion (300 mg/day) or placebo. Outcomes will be assessed at baseline and the 12-week follow-up. The primary outcome, fatigue, will be measured with the Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-F). Secondary outcomes include quality of life, depression, and drug tolerability. Exploratory outcomes include cognition and symptomatology. Potential biological mechanisms and genetic moderators of cancer-related fatigue will also be explored. Discussion: This study is the first placebo-controlled trial to our knowledge to evaluate bupropion for cancer-related fatigue. Positive results could revolutionize the treatment of cancer-related fatigue, as bupropion is safe, inexpensive, widely-available, and may be more tolerable and acceptable for many patients than current, limited treatment options

Risk of chemotherapy-induced neutropenic complications when treating patients with non-Hodgkin lymphoma

<p><b>Introduction</b>: Myelosuppression induced by cancer chemotherapy is associated with considerable morbidity and mortality. Febrile neutropenia (FN) represents an oncologic emergency requiring immediate evaluation and treatment. Resulting chemotherapy dose reductions or delays may compromise disease control and survival. While non-Hodgkin lymphoma (NHL) represents a potentially curable malignancy, there are limited data on the risk of neutropenic complications. This review represents a systematic search and evidence summary of neutropenic complications reported in randomized controlled trials (RCTs) published over the past decade in adults with NHL receiving myelosuppressive chemotherapy.</p> <p><b>Areas covered</b>: Data captured include the chemotherapy regimen and dosing, the type of NHL, sample size, myeloid growth factor (MGF) use, and myelosuppression including FN and severe neutropenia and infection.</p> <p><b>Expert opinion</b>: Rates of neutropenic complications for commonly utilized chemotherapy regimens vary considerably across studies with FN reported in only one-fourth of study arms. Further challenges in interpreting reported rates are the variable and inconsistent use of MGF support and little or no information on delivered chemotherapy dose intensity. Considerable change in regimens, study populations and reporting of neutropenic events as well as the use of MGF was observed over the decade of RCTs reported. Complete and accurate reporting of treatment-related toxicities in patients receiving cancer chemotherapy is essential in both clinical trials and clinical practice.</p

Economic Analysis of Prophylactic Pegfilgrastim in Adult Cancer Patients Receiving Chemotherapy

AbstractObjectivesNeutropenia and its complications, including febrile neutropenia (FN), are a common side effect of cancer chemotherapy. Results of clinical trials showed that prophylactic use of granulocyte colony-stimulating factors (G-CSF) is effective in preventing FN. In this study, the cost effectiveness (measured as cost per quality-adjusted time [days]) of three treatment alternatives were evaluated: no G-CSF, filgrastim administered daily for 7–12 days after chemotherapy, and a pegylated form of G-CSF pegfilgrastim, administered once per cycle.MethodsA cost-utility model based on standard clinical practice of treating FN with immediate hospitalization or with ambulatory treatment, from a societal perspective was developed. Direct medical cost estimates for hospitalization were derived from claims data reported by 115 US academic medical centers. Indirect medical costs, productivity costs, probabilities, and utilities are based on published literature. Results were subjected to sensitivity analyses and95% confidence intervals are based on a Monte Carlo simulation.ResultsMean estimated costs/day of hospitalization were $1984 (SD$1040, N = 24,687) for surviving patients and $3139 (SD$2014, N = 1437) for dying patients. Under baseline conditions, pegfilgrastim dominated both filgrastim and no G-CSF, with expected costs and effectiveness of $4203 and 12.361 quality adjusted life-days (QALDs) for no G-CSF,$3058 and 12.967 QALDs for pegfilgrastim, and $5264 and 12.698 QALDs for filgrastim.ConclusionsThis cost-utility analysis provides strong evidence that pegfilgrastim is not only cost-effective but also cost-saving in most common clinical and economic settings. There appear to be both clinical and economic benefits from prophylactic administration of pegfilgrastim

Hodgkin lymphoma treatment with ABVD in the US and the EU: neutropenia occurrence and impaired chemotherapy delivery

In newly diagnosed patients with Hodgkin lymphoma (HL) the effect of doxorubicin, bleomycin, vinblastine and dacarbazine (ABVD)-related neutropenia on chemotherapy delivery is poorly documented. The aim of this analysis was to assess the impact of chemotherapy-induced neutropenia (CIN) on ABVD chemotherapy delivery in HL patients