New Directions in Chemotherapy-Induced Neutropenia - Episode 5
A historical overview regarding the development and role of granulocyte colony-stimulating factors as prophylaxis for chemotherapy-induced neutropenia and recommendations for use.
Lee Schwartzberg, MD, FACP: We have had effective prophylaxis against CIN [chemotherapy-induced neutropenia] for the past 30 years, with the advent of recombinant growth factors, predominantly G-CSF, granulocyte colony-stimulating factor. Studies done in the early ’90s with highly myelosuppressive chemotherapy showed that we could reduce, but not eliminate, CIN with the delivery of G-CSF given after chemotherapy that was heavily myelosuppressive. We also in early days used GM-CSF [granulocyte-macrophage colony-stimulating factor], but in the clinic that’s rarely used today because of other toxicities, and it probably doesn’t work as well as a broader growth factor stimulant, not just of granulocytes.
For the last 30 years, we’ve had either short-acting G-CSF, which is administered daily after chemotherapy, usually starting at least 24 hours after chemotherapy and continued until the [neutrophil] count recovery, which is typically around 10 days afterward. We give G-CSF as a daily injection, and for the last 20 years we’ve had a long-acting version of G-CSF, which is pegfilgrastim, which allows dosing much more conveniently, only once because it has decreased clearance through the kidneys and is self-regulated. Once the white blood cell count comes back, it metabolizes the drug. Giving G-CSF has revolutionized the approach to CIN because [it can give patients prophylaxis] against CIN when they’re getting a myelosuppressive regimen, with an appropriate G-CSF dose.
The NCCN [National Comprehensive Cancer Network] has a growth factor guideline committee, and it recommends prophylaxis with G-CSF for any patient who is receiving a myelosuppressive regimen where that risk of febrile neutropenia [FN] would be at least 20%, and particularly when it’s in a curative regimen. In a palliative regimen, another alternative would be to reduce the dose in subsequent cycles, although it must be noted that that might decrease the efficacy, even in a palliative setting.
For FN risk greater than 20% by chemotherapy, it’s recommended. For patients in the intermediate range, which is considered 10% to 20% risk from the chemotherapy itself, patient risk factors should be taken into account, and based on the clinician and patient’s decision together, consider growth factor prophylaxis starting with the first cycle of therapy, importantly. For regimens that have less than a 10% risk, the NCCN does not recommend growth factor support, even if there are patient risk factors, because it’s relatively low.