Sveikata, A., Liutkauskiene, S., Juozaityte, E., Characiejus, D., Tamosaityte, L., & Sestakauskas, K. (2011). An open-label multicenter safety, tolerability, and efficacy study of recombinant granulocyte colony-stimulating factor in the prevention of neutropenic complications in breast cancer patients. Medicina, 47, 428–433.

The purpose of the study was to evaluate the safety and efficacy of a new rG-CSF in patients receiving chemotherapy for breast cancer.
 

Patients receiving either doxorubicin and docetaxel or docetaxel alone were entered into the study.  Patients were given rG-CSF  5 mcg/kg per day by subcutaneous injection starting on day 2 of each chemotherapy cycle, 24 hours after chemotherapy completion, that continued for either five days or until absolute neutrophil count (ANC) was greater than 1.5 x 10⁹/L. The study duration was 13 months. Severity and incidence of adverse events and antibody formation to the study drug were done. Study endpoints were incidence and duration of febrile neutropenia, duration of fever, chemotherapy cycle delays or dosage reductions, and incidence of antibiotic therapy.

• 50 patients were studied.
• Mean age of the participants was 53.54 years (SD = 10.47).
• All participants were female.
• All had breast cancer; 44% were chemotherapy naïve.

Multiple site in Lithuania.

Active antitumor treatment

Open label phase IV

• Febrile neutropenia defined as axillary temperature greater than 38.5ºC and ANC less than 0.5 x 10⁹/L.
• Common Toxicity Criteria
   

273 cycles of chemotherapy were examined. Mean duration of rG-CSF administration per cycle was 6.3 days. Eight patients withdrew from the study for various reasons. Most adverse events were associated with the chemotherapy. The most frequent grade 3–4 toxicity was neutropenia. Incidence of  grade 4 neutropenia was 47% in cycle 1 and 42% overall in patients receiving docetaxel/doxorubicin and 29% in cycle 1 and 21% overall in patients receiving docetaxel only. Most frequent study drug-related adverse events were bone pain and leukocytosis (21%), headache and musculoskeletal pain (14%), and back pain (7%).  Only bone pain was seen to be of more than mild-to-moderate severity. No neutralizing antibodies were found. Total incidence of febrile neutropenia (FN) was 14%. Mean duration of FN was 2–2.3 days. Mean duration of fever was 2.1–3.6 days depending on chemotherapy group. There was an overall incidence of chemotherapy delays or dosage changes of 1%. Overall, 20% of patients received IV antibiotics.

Overall, the study drug showed similar efficacy to other colony-stimulating factors and appeared to be well tolerated.

• Small sample (less than 100 participants)
• Risk of bias (no control group) 
• Risk of bias (no blinding)  
• Risk of bias (no random assignment)
• Findings were not generalizable
• It is not clear if analysis accounted for study withdrawals as percentages shown assume initial study sample size. Intent to treat analysis is not clearly stated. Open label design and no direct comparison with other formulations. These findings may not be generalizable to patients receiving other chemotherapeutic agents.

 Findings demonstrate effects of another G-CSF formulation.