Extensive-Stage Small Cell Lung Cancer and Chemotherapy-Induced Myelosuppression - Episode 2
Drs Charu Aggarwal and Jared Weiss react to the impact that chemotherapy-induced myelosuppression can have on patients with extensive-stage small cell lung cancer, as well as the overall health system.
Jared Weiss, MD: Myelosuppression is not just about a number; it’s about what the number conveys a risk of. Let’s go through each of the major counts. For neutrophils, the major downstream sequela is febrile neutropenia. Strictly defined it’s the combination of a low neutrophil count and a fever. In practice, what it prompts is antibiotics and frequently hospital admission. And of course, sometimes these turn into severe, even life-threatening or ending, infection. For anemia, our patients feel tired and short of breath, and it often requires treatments with transfusions, which have adverse effects such as transfusion-related reactions or volume overload. As well, it’s immunosuppressive to receive someone else’s blood. When the platelets go low, that’s thrombocytopenia. We don’t see a lot of major bleeding in small cell [lung cancer] but what does happen is dose delays or dose reductions that can cause patient anxiety, increased cost, and perhaps reduced efficacy of therapy.
Charu Aggarwal, MD, MPH: I would say that one of the main linkages between myelosuppression and cancer-related treatments is that we may need to either hold treatment, or delay treatment, or directly lead to a dose reduction. Now, this we know can directly impact outcomes because we are compromising the way that chemotherapy or other regimens are administered to our patients.
When a patient presents to me who I have not used prophylactic growth factor support in, but prior to their subsequent cycle I notice that the patient has significant myelosuppression, I ask whether there was a dose-limiting event in the past or a neutropenic event. And if there was, I would recommend that we use growth factor support right away with subsequent cycles of chemotherapy.
However, if there was no febrile neutropenia, and this is the first time I’m noticing something, and this is not a highly myelosuppressive regimen, I may continue at the same dose and then reconsider. But often, for my elderly patients with other risk factors that I discussed with you earlier, more often than not I am coming in with growth factor support based on how the outcomes panned out after the previous cycle. And at what level do I consider? I would say an absolute neutrophil count of less than 1000 [per μL] is my threshold to hold treatment, and I would get to a point where I want to be above 1000 [per μL] before I begin the next treatment, and I use the threshold of platelets of 100,000 [per μL].
Jared Weiss, MD: The effects of myelosuppression on the quality of life and acceptance of treatment are understated. And this is especially true of fatigue. There was a great poster at ISPOR [the International Society for Pharmacoeconomics and Outcomes Research meeting] that did the math on some of this. It started looking at occurrence of medical events and looked at a 4-year period. Things weren’t very different across the 4 years, so I’ll give the summary measures. But anemia occurred in 72% of patients; neutropenia in 45%; thrombocytopenia in 27%; and pancytopenia in just under a quarter of patients. Also, 74% of chemotherapy-treated patients experienced at least in 1 inpatient admission associated with myelosuppression. The hospital admissions for myelosuppression most frequently reported were for anemia at 53% of patients, followed by neutropenia at one-third; thrombocytopenia at 17%, and pancytopenia at 14%. Of course, admission is a big deal for patient quality of life and for expense. There’s also an interesting survey that asked patients who had a myelosuppressive event how much it affected them. This was not restricted to lung cancer. Among the 301 survey participants, fatigue was the most frequently reported adverse effect of chemotherapy. And 55% of participants rated fatigue as highly bothersome, meaning 9 or 10 on a 1 to 10 scale. Participants rated symptoms associated with chemotherapy-induced myelosuppression, including fatigue but also weakened immune system, bleeding or bruising, shortness of breath, as being bothersome. And they were at least as bothersome as other adverse effects including alopecia, neuropathy, and nausea/vomiting. Overall, 24% to 43% of participants thought that chemotherapy-induced myelosuppressive symptoms had a negative impact on their daily lives, including their ability to complete tasks at home and work and to socialize.
Transcript edited for clarity.