GRACE :: Cancer Treatments / Symptoms & Support? Blog Archive

Febrile Neutropenia?Part II, Prevention and Treatment

Preventing F & N

There are three basic ways to prevent febrile neutropenia. When appropriate, a regimen with a smaller chance of causing F & N can be chosen. There are two other options: the use of drugs to bring the neutrophil count up, and prophylactic (preventative) antibiotics.

There are two drugs in common usage for lung cancer that can raise the neutrophil count. The first is called neupogen and the second neulasta. I?ve linked to the Amgen page on neulasta because I think that it?s actually pretty helpful. Granted, it?s there to sell more neulasta, but in trying to do so, the page on blood counts makes two very valid points about low blood counts: they can cause direct problems by causing infection, and they can interfere with needed chemotherapy.

How do these drugs work? As we discussed above, the bone marrow is a factory for making blood cells, including the subtype of white blood cells we?ve been talking about?neutrophils. Neupogen and neulasta send an artificial signal to the bone marrow to make more neutrophils, hurry up and get them ready, and release them into the blood. Neuopgen is given every day until the counts have recovered, typically a week or two. Neulasta is a long-acting drug that you only need to give once.

Both drugs, when utilized, are typically started 24 hours after chemotherapy. The package insert for both says that they shouldn?t be used for 14 days before chemotherapy. The reason for this is theoretical?doctors fear that if they send the bone marrow a signal for the blood-making stem cells to divide while chemo is still around, they will risk poisoning these stem cells, actually making the problem worse. This makes a lot of sense, but is it true? While coming back the next day is only a minor nuisance for some of my patients, for others it represents a significant hardship. What do the data say?

As usual, they are not definitive. Four randomized studies compared same day neulasta administration to the usual 24 hours post administration. Studies were done in patients with breast cancer, Non-Hodgkin?s lymphoma, NSCLC and ovarian CA. Overall, there was no clear harm from giving the neulasta the same day:

As a result of this study, I became less dogmatic about always using neulasta the day after chemo. If a patient has to drive several hours to come to my infusion room and there is no option for administration closer to home, I talk to them about same-day neulasta. But, I don?t do so without some schpilkas. Neutropenia duration was actually longer in the breast study and the lymphoma study with same day dosing. This is important, because risk of F&N goes up with neutropenia duration. Further, none of these studies looked at patients for long followup. Did the same-day groups have more problems with counts in future cycles? We don?t know. My practice, when possible, remains to give the neulasta the next day.

Who should get prophylactic neulasta? While the drug can prevent febrile neutropenia, it can also cause side effects. The patient product information sheet lists all kinds of side effects, but I prefer patient-reported information. Patients most commonly complain of bone pain and a flu-like syndrome. Plus, there?s the inconvenience of having to come to the doctors office the day after chemo, a minor nuisance for some but a big problem for others. Both ASCO (American Society of Clinical Oncology) and NCCN (national comprehensive cancer network) guidelines recommend neulasta prophylaxis when the risk of febrile neutropenia reaches 20% and I think that this guideline is very reasonable.

Now, on to things that don?t work. Preventative antibiotics are rarely used in lung cancer patients. The reason is that the duration and severity of neutropenia with lung cancer regimens is just not deep or long enough to justify the risk of antibiotic side effects and the risk of antibiotic resistance. There are certainly specific cases where I consider it, but routine prophylactic antibiotics would be more likely to harm than to help the average lung cancer patient. Patients often ask about cloistering themselves at home to try to avoid infections while they are neutropenic. Neither data nor my experiences suggest that this works. The biggest reason is that infections with F&N in lung cancer regimens are largely from bugs that are everywhere, rather than from bugs that you specifically pick up from someone. It makes sense to practice good hand hygiene, and to avoid people who are actively sick. It?s unclear that avoiding your healthy grandchildren will help you to live a day longer (unless their mischief is so bad that it shortens your life!) There?s a very important caveat to what I?m saying?while it applies well to lung cancer and head/neck cancer regimens, none of this is true for hematologic cancers (leukemia, lymphoma, bone marrow transplant patients) and is not oriented even towards patients with other solid cancers who get more intensive regimens (such as sarcoma). This conversation is very head/neck and lung centered because, at the time of writing, GRACE is an exclusively head/neck and lung cancer site.

Treatment of febrile neutropenia

In the doctor?s office or hospital, the doctor will look for a source of infection. This workup typically includes history taking (questions that could point to a source, such as, ?Does it burn when you pee?? and ?Are you coughing??), physical examination, imaging, and cultures of urine and blood. If a source can be found, then the antibiotic regimen can be tailored to the bug in question. If not, broad-spectrum antibiotics that are active against most suspected bugs are given. If the suspected source is a line (such as a PICC) then strong consideration must be given to removing it.

The use of neupogen and neulasta to treat febrile neutropenia has not been studied nearly as much as their use to prevent infections. A meta-analysis suggested that their use can shorten length of hospitalization and time to recovery of neutrophil counts, but not survival. NCCN recommends consideration of these drugs if certain risk factors are present. I?ve re-ordered them from the NCCN?s list into the order in which they influence my thinking:

? Sepsis (a severe inflammatory syndrome associated with infection)

? Pneumonia

? Invasive fungal infection

? Neutropenia expected to be more than 10 days in duration

? Severe neutropenia (absolute neutrophil count < 100/mcl)

? Hospitalization at the time of fever

? Other clinically documented infections

? Age > 65 years

? Prior episode of febrile neutropenia

Can any patient with febrile neutropenia be managed at home? Most patients hate being admitted to the hospital. Beyond being unpleasant, admission to the hospital can interfere with sleep, reduce contact with loved ones, and be a great place to catch resistant bugs. To me, the following factors make me more comfortable with considering outpatient treatment of F&N:

? Known or strongly suspected source

? Reliable patient (especially including willingness to go the ER for any worsening)

? Presence of reliable partner (ability to monitor patient, willingness to insist on ER trip if things get worse)

? Patient does not seem super sick?this is a combination of what my patient tells me, my physical examination (especially vital signs) and my gut feeling

? Short expected duration of neutropenia (biggest factor is regimen and current timing from regimen, but patient history with counts also matters)

? Mild severity of neutropenia (counts aren?t super low)

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Source: http://cancergrace.org/cancer-treatments/2011/05/13/1591/

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