Chemotherapy Use & Chemotherapy-Induced Myelosuppression

Gary H. Lyman, MD, MPH, FASCO, FRCP: Chemotherapy, despite the excitement around targeted therapies and immunotherapies that we all share, remains the backbone of systemic cancer treatment today and is likely to remain as such for the foreseeable future. We know that about 1 million patients receive chemotherapy annually in the United States. Therefore, it is a treatment that we need to continue to fully understand. Most important, we need to manage the adverse effects that occur.

These are very active but very myelosuppressive agents. We know they attack stem cells, both healthy and diseased—tumor stem cells. They can damage hematopoietic progenitor cells at the origin of hematopoietic cells and right through committed precursors. Of course, it can have an impact on all lineages. The hematopoietic stem cells give rise to not only neutrophils and infection-fighting cells but red cells resulting in anemia. They give rise to platelets. If they’re severely low, it may lead to bleeding issues. This major dose-limiting toxicity of cytotoxic chemotherapy remains that of the damage to stem cells in all 3 lineages, and it’s important that we optimize the methods to preserve those healthy stem cells in the normal cells throughout the course of treatment to minimize these complications.

Because the cytotoxic nature of chemotherapy has an impact on all 3 lineages, in addition to immune cells in the body and T cells in particular, it is imperative that we understand the risk of neutropenia, particularly febrile neutropenia, which is tantamount to an infection. If the neutropenia is severe, it can be life threatening. This often results in hospitalization. Although most patients survive those infections, we know that there is still, based on our national data of hospitalized patients with febrile neutropenia, a real mortality rate that may reach the 6%-to-8% range across all patients with cancer receiving chemotherapy.

In addition, a major adverse effect of chemotherapy is fatigue, and that often relates to anemia. Of course, it may be further worsened by the cancer itself or any bleeding associated with the cancer. But because the red cell precursors are impacted just like the neutrophils, anemia can be a problem that may require intervention with transfusions or other therapeutic interventions.

We are also concerned about thrombocytopenia, which is less common. We’re trying, as part of therapy, to suppress all these lineages by impacting the marrow itself. But if thrombocytopenia does occur and it becomes profound enough, bleeding risk is a real concern. We can give platelet transfusions, and they’re usually reserved for very low platelet counts. We now have some thrombopoietic agents that are available and FDA approved. But they’re not used until we see more severe levels of thrombocytopenia that put the patient at risk for bleeding complications.

The impact of cytotoxic chemotherapy on the immune system is something we’ve recognized more recently. We know cancer can suppress the immune system as well as other therapies like corticosteroids. We also now understand that cytotoxic therapy may impact the immune response to either the cancer or to infectious conditions.

All of these—anemia, neutropenia, thrombocytopenia, and immunosuppression—may result from cytotoxic chemotherapy, which remains the mainstay of cancer systemic therapy.

The cytotoxic effects of chemotherapy obviously have a direct impact on the patient. While we have focused on the clinical aspects and the complications that may ensue, the patient is the one who’s most profoundly impacted. Recent surveys have clearly demonstrated that across solid tumors—breast cancer, lung cancer, colorectal cancer—anemia, leukocytopenia, thrombocytopenia, and neutropenia all occur and are recognized by patients as the cause of many of their symptoms. In fact, the vast majority of patients surveyed receiving cytotoxic chemotherapy indicate that chemotherapy-induced myelosuppression can have either a moderate or severe impact on their quality of life. Two-thirds of these patients particularly report fatigue as the biggest issue.

These are really part of the patient experience of going through cytotoxic therapy. Again, this is something we want to lessen by trying to preserve stem cells. Clearly, the physical aspects that we see often relate to the fatigue, to the performance status of the patient. The likelihood of these factors having a profound impact in patients clearly relates to the clinical scenario, the stage of the disease, and then of course the intention of treatment, regardless of whether the intention is curative in patients with early stage responsive malignancies or more palliative, for which the main goal of therapy is to minimize the effect of the cancer and the treatment on the patient in preserving patient preferences.

All of these have an impact on quality of life. We can talk about cost a little later. But we can’t forget what a major impact this is on the patient who goes through cytotoxic therapy.

Transcript Edited for Clarity