Targeted Anti-Cytokine Therapy

• Cohort A: Six patients received docetaxel (43 mg/m²) weekly for six weeks every eight weeks.
• Cohort B: Six patients received docetaxel weekly combined with etanercept (25 mg subcutaneously) twice weekly in addition to the docetaxel dosing schedule observed in Cohort A.
• Cohort C: Six patients received docetaxel at a higher dose (52 mg/m²) weekly combined with etanercept (25 mg subcutaneously) twice a week for six weeks.
• Cohort D: Eight patients received docetaxel (52 mg/m²) weekly combined with etanercept (25 mg subcutaneously) twice a week and G-CSF (5 ug/kg per day for four consecutive days starting the day after each docetaxel administration).
• Outcomes were assessed at baseline and each week.

N = 28

MEDIAN AGE = 56 years

AGE RANGE = 25–83 years

MALES = 17

KEY DISEASE CHARACTERISTICS: Most had received previous chemotherapy and/or radiotherapy and had multiple disease sites. The most common disease site was non-small-cell lung.

EXCLUSION CRITERIA: Patients were excluded if they were scheduled for major surgery, radiotherapy, or chemotherapy within 28 days of study entry or had brain metastases, serious infections, or psychiatric disorders that would interfere with consent or follow-up; pre-existing moderate-to-severe peripheral neuropathy; or cardiac disease. Pregnant or lactating women also were excluded.

• PHASE OF CARE: Active treatment

• Pilot feasibility study

• National Cancer Institute (NCI) fatigue grade assessment
• Fatigue Symptom Inventory (FSI)

Patients randomly were selected to receive etanercept/docetaxel. Less fatigue was self-reported in comparison to patients who received docetaxel only (p < 0.001). The FSI Interference score of Cohort A was significantly greater than the score of Cohort B (p < 0.001). Patients receiving additional cycles for treatment (Cohorts B,C, and D) did not experience worsening fatigue.

• Pilot study and therefore lacking a neutral comparison group
• Small sample size
• Fatigue assessment endpoints were not predetermined

In the original protocol, infliximab was given as an intravenous infusion at 5 mg/kg over a two-hour period, followed by a two-hour observation period, at baseline and two, four, and every four weeks after that if improvement was demonstrated. After a patient suffered a serious infection following the week 2 infusion, the dosing regimen was amended to 5 mg/kg at week 0 and every four weeks after if improvement was observed. The first five patients were treated under the original protocol, and the next 12 were treated according to the amended protocol. Patient outcomes were evaluated at every time point.

• The sample was comprised of 17 patients with end-stage cancer.
• Mean age was 63.5 years.
• The majority of the patients were male (76.5%) and had multiple cancer diagnoses, with the most common being renal cell carcinoma (23.5%) and nonsmall cell lung carcinoma (NSCLC) (23.5%).
• Patients were excluded if they had a reversible cause of fatigue (i.e., anemia, hypercalcemia, hyponatremia, or hypothyroidism) or had major surgery, chemotherapy, or radiotherapy within four weeks of study enrollment, which were medical contraindications for infliximab treatment.

Outpatient, daytime therapy clinics for specialist palliative care at the Marie Curie Hospice, United Kingdom

Patients were undergoing the palliative phase of care.

This was an open-label, pilot study.

Fatigue Severity Scale (FSS)

The infliximab intervention did not show an overall improvement of fatigue in patients. However, a small cohort of six patients showed an improvement in FSS scores over time with repeated infliximab infusions, although this difference did not reach statistical significance. The six patients shared a similar profile of NSCLC that was progressive through chemotherapy and received the amended protocol treatment.

• The study had a small sample size.
• The stuck lacked a neutral comparison group.