ABSTRACT: Functional iron deficiency may impair response to erythropoiesis-stimulating agents (ESAs) in iron-replete patients with chemotherapy-associated anemia (CAA). This study evaluated whether coadministration of parenteral iron improves ESA efficacy in patients with CAA.
This prospective, multicenter, randomized trial enrolled 502 patients with hemoglobin (Hb) less than 11 g/dL who were undergoing chemotherapy for nonmyeloid malignancies. All patients received darbepoetin alfa once every 3 weeks and were randomly assigned to receive either ferric gluconate 187.5 mg intravenously (IV) every 3 weeks, oral daily ferrous sulfate 325 mg, or oral placebo for 16 weeks.
There was no difference in the erythropoietic response rate (ie, proportion of patients achieving Hb ≥ 12 g/dL or Hb increase ≥ 2 g/dL from baseline): 69.5% (95% CI, 61.9% to 76.5%) of IV iron-treated patients achieved an erythropoietic response compared with 66.9% (95% CI, 59.1% to 74.0%) who received oral iron and 65.0% (95% CI, 57.2% to 72.3%) who received oral placebo (P = .75). There were also no differences in the proportion of patients requiring red cell transfusions, changes in quality of life, or the dose of darbepoetin administered. Adverse events (AEs) tended to be more common in the IV iron arm: grade 3 or higher AEs occurred in 54% (95% CI, 46% to 61%) of patients receiving IV iron compared with 44% (95% CI, 36% to 52%) who received oral iron and 46% (95% CI, 38% to 54%) who received oral placebo (P = .16).
In patients with CAA, addition of IV ferric gluconate to darbepoetin failed to provide additional benefit compared with oral iron or oral placebo.
Journal of Clinical Oncology 01/2011; 29(1):97-105. · 18.37 Impact Factor
ABSTRACT: Epidermal growth factor receptor (EGFR) inhibitors are effective cancer therapies, but they are reported to cause a rash in >50% of patients. In the current study, the authors examined the use of tetracycline for rash prevention.
This placebo-controlled, double-blinded trial enrolled patients who were starting cancer treatment with an EGFR inhibitor. Patients could not have had a rash at the time of enrollment. All patients were randomly assigned to receive either tetracycline at a dose of 500 mg orally twice a day for 28 days versus a placebo. Patients were monitored for rash (through monthly physician assessment and weekly patient-reported questionnaires), quality of life (using the SKINDEX-16, a skin-specific quality of life index), and adverse events. Monitoring occurred during the 4-week intervention and then for an additional 4 weeks. The primary objective of the current study was to compare the incidence of rash between the study arms, and the enrollment of 30 patients per arm provided a 90% probability of detecting a 40% difference in incidence with a P value of .05 (2-sided).
A total of 61 evaluable patients were enrolled. The 2 treatment arms were well balanced with regard to baseline characteristics, dropout rates, and rates of discontinuation of the EGFR inhibitor. The incidence of rash was found to be comparable across treatment arms. Physicians reported that 16 patients treated with tetracycline (70%) and 22 patients treated with placebo (76%) developed a rash (P = .61). Tetracycline appears to have lessened the rash severity, although the high dropout rates invite caution when interpreting these findings. By Week 4, physician-reported grade 2 rash (using the National Cancer Institute's Common Terminology Criteria for Adverse Events [version 3.0]) occurred in 17% of tetracycline-treated patients (n = 4 patients) and in 55% of placebo-exposed patients (n = 16 patients) (P = .04). Patients treated with tetracycline reported better scores, as per the SKINDEX-16, on certain quality-of-life parameters such as skin burning or stinging, skin irritation, and being bothered by the persistence/recurrence of a skin condition. Adverse events were found to be comparable across treatment arms.
In the current study, tetracycline was not found to prevent EGFR inhibitor-induced rashes and therefore cannot be clinically recommended for this purpose. However, preliminary observations of diminished rash severity and improved quality of life suggest this antibiotic merits further study.
Cancer 06/2008; 113(4):847-53. · 4.77 Impact Factor
ABSTRACT: Up to 90% of small cell lung cancer (SCLC) patients suffer cognitive dysfunction. Since donepezil and vitamin E have been somewhat successful in treating other dementias, this study tested the hypothesis that these agents can prevent cognitive decline in SCLC patients. Because accrual was poor, this trial also offered opportunities for suggesting other study designs for future clinical trials on cognitive dysfunction in this group of patients.
This double blind, placebo controlled trial tested oral donepezil 5 mg/day (with dose escalation to 10 mg after 1 month) and oral vitamin E 1,000 IU/day in SCLC patients after completion of all cancer therapy, including prophylactic cranial irradiation (PCI). Cognition, adverse events, and quality of life were assessed throughout the study period.
Only nine of 104 patients enrolled over 15 months (four donepezil and vitamin E-treated versus five placebo-exposed), and thus no definitive conclusions could be drawn. Nonetheless, the only patient who manifested a precipitous decline in cognition was taking donepezil and vitamin E. There was also a slight trend of increased gastrointestinal side effects among donepezil and vitamin E-treated patients. There were no notable differences in cognitive stability, adverse events, or quality of life between treatment arms.
These preliminary findings do not provide enthusiasm for testing donepezil and vitamin E in the manner undertaken here for preventing cognitive dysfunction in SCLC patients. Eligibility criteria and timing of trial intervention are discussed as potential impediments to successful trial completion.
Supportive Care Cancer 02/2005; 13(1):66-9. · 2.60 Impact Factor