Neulasta Treatment of Neutropenia Improves Treatment

Understand the role of Neulasta treatment of Neutropenia to prevent infection and improve chemotherapy treatment.

by Dr. C.H. Weaver M.D. updated 7/2019

What is neutopenia and why is it important to prevent?

Chemotherapy remains the cornerstone of treatment for many patients with cancer. Unfortunately, chemotherapy is associated with side effects, including low levels of white blood immune cells-a condition referred to as neutropenia. Patients with neutropenia can become susceptible to infection with bacteria, viruses, and/or fungus. Among patients with neutropenia accompanied by fever (febrile neutropenia [FN]), even the slightest infection can become life-threatening. Patients with FN typically must have their chemotherapy treatment doses delayed or reduced, which decreases the chance for the best outcomes.(1)

Neulasta is a type of white blood cell growth factor of booster.

Fortunately, neutropenic patients can receive blood cell boosters (growth factors) such as Neulasta, which are given by injection during chemotherapy cycles. Neulasta has the ability to reduce infections, prevent hospitalizations, lower medical cost, avoid dose delays, and prevent death associated with infection in neutropenic patients. The FDA has approved Neulasta to be given at least 24 hours following initiation of chemotherapy.(1-8)

How does Neulasta work?

Neulasta® belongs to a group of drugs called colony stimulating factors. Neulasta® stimulates the growth of neutrophils, a type of white blood cell, which are important immune cells that fight infection caused by bacteria, viruses or fungus. Neutrophils can be damaged by chemotherapy and leave patients susceptible to severe infection. Neulasta® works by binding to areas on immature blood cells, which stimulates the blood cells to grow, reproduce and mature into neutrophils. Neulasta® is a long-acting form of another commonly used colony stimulating factor, Neupogen® (filgrastim), meaning it stays active in the body for a longer time than Neupogen®.

What are the side effects of Neulasta?

The following side effects may occur in individuals treated with Neulasta® but occur in less than 1/3 of individuals.

  • Bone pain
  • Changes in some laboratory tests, which tend to normalize following treatment
  • Soreness or tenderness at the injection site

What can patients do to alleviate bone pain associated with Neulasta injection?

Tylenol (acetaminophen) and NSAID'S like Naproxen both help reduce bone pain once it occurs. Claritin (loratadine) taken prior to Neulasta injection can help prevent bone pain by blocking histamine release.(1,2)

What do the clinical studies show about Neulasta?

Early Use of Neulasta® is Superior to Later Use In Elderly Patients Undergoing Chemotherapy

Elderly patients are also considered to be at a higher risk of developing neutropenia than their younger counterparts. Researchers from the H. Lee Moffitt Cancer Center conducted a clinical trial including 852 elderly patients undergoing chemotherapy for either solid tumors (cancers not originating from the blood or lymph system) or non-Hodgkin’s lymphoma (NHL). Patients were divided into two groups: one group received Neulasta following their first cycle of chemotherapy (proactive use), while the other group received Neulasta at the discretion of their physician (reactive treatment).

  • The incidence of FN was significantly lower among patients in the proactive group compared with those in the reactive group.
  • Hospitalizations for FN or neutropenia were reduced by half among the proactive versus reactive groups.
  • Among patients with solid tumors, antibiotic use was reduced among the proactive versus reactive groups.

The researchers concluded: “Neulasta should be used proactively in elderly cancer patients to support the optimal delivery of standard chemotherapy.” Elderly patients undergoing chemotherapy may wish to speak with their physician regarding their individual risks and benefits of receiving proactive Neulasta.(2)

Neulasta Reduces Incidence of Neutropenia and Infections in Breast Cancer Patients and Prevents Hospitalizations

According to results presented at the Multinational Association of Supportive Care in Cancer (MASCC) Annual Meeting, Neulasta administered during the first and subsequent cycles of chemotherapy significantly reduces the risk of neutropenia and associated complications in breast cancer patients.(8)

Researchers from Memphis, Tennessee conducted a clinical trial to compare the use of Neulasta® to placebo (inactive substitute) in patients with breast cancer undergoing chemotherapy. This trial included 928 patients who were being treated with Taxotere®-based chemotherapy. Half of the patients received Neulasta® on the first and subsequent cycles of chemotherapy, while the other half received placebo. Only 1% of patients who were treated with Neulasta® developed febrile neutropenia, compared with 17% of patients who received placebo. Febrile neutropenia occurred most often in the first cycle of chemotherapy (65%) in the group of patients who received placebo. Additionally, only 1% of patients treated with Neulasta® required hospitalization, compared with 14% of patients who received placebo. Anti-infectives delivered into a vein (intravenous) were required in only 2% of patients treated with Neulasta®, compared with 10% of patients who received placebo.

The researchers concluded that the preventive use of Neulasta® significantly decreases febrile neutropenia, hospitalizations, and intravenous anti-infective use when used in the first and subsequent cycles of chemotherapy that is only moderately associated with the development of febrile neutropenia in breast cancer patients. The presenter also stated that results of this trial provide evidence that preventive use of agents such as Neulasta® may ultimately become more widely used in patients undergoing chemotherapy.(5,6)

Meta-Analysis Reveals that Neulasta® Can Significantly Reduce the Risk of Death Caused by Infection in Cancer Patients

According to results recently presented at the 17th MASCC/ISOO international symposium, the granulocyte-colony stimulating factor (G-CSF) agents Neupogen® (filgrastim) and Neulasta® (pegfilgrastim) significantly reduce the risk of death caused by infection in cancer patients undergoing therapy.

Neulasta and Neupogen are agents that stimulate the production of immune cells in the body. Neulasta reduces or even completely prevents the development of neutropenia and its associated complications in patients undergoing chemotherapy. Neulasta is currently FDA-approved for patients who are receiving chemotherapy associated with a significant risk of developing febrile neutropenia (neutropenia accompanied by fever). The drug is designed so that only one injection is given per chemotherapy cycle. Researchers continue to evaluate which patients benefit the most from treatment with Neulasta, as well as to determine whether its use can completely prevent the development of neutropenia associated with chemotherapy. Currently, most physicians reserve the use of Neulasta for patients who are considered to be at high risk for developing neutropenia or for those who have already developed neutropenia. However, recent research suggests that the development of neutropenia and its associated complications may be greatest during the first cycle of chemotherapy. Therefore, prevention of neutropenia is crucial during the initial cycle of chemotherapy treatment.

Researchers from the United States recently conducted a data analysis of 14 clinical trials involving over 3,000 patients with cancer. These trials involved patients who were undergoing treatment for cancer. Some received G-CSFs such as Neulasta or Neupogen to prevent neutropenia, while control groups received no preventative agents. Overall results showed a reduced risk of febrile neutropenia in patients treated with CG-CSFs: 0 percent to 63 percent in the G-CSFs groups veruse 7 percent to 78 percent in control groups. In other words, patients treated with G-CSFs had almost half (48 percent) the risk of infection-related death. Furthermore, Neulasta provided superior results to other G-CSFs in these studies.

The researchers concluded that prevention with G-CSFs, particularly Neulasta, in patients with cancer who are undergoing therapy appears to significantly reduce the risk of infection-related death compared to no prevention for neutropenia. Patients undergoing therapy for cancer may wish to speak with their physician regarding their individual risks and benefits of the preventive use of Neulasta or other G-CSFs.(11)

Neulasta® Allows for More Effective Chemotherapy in Non-Hodgkin’s Lymphoma

The growth factor Neulasta® allows patients to tolerate more dose-dense chemotherapy in the treatment of non-Hodgkin’s lymphoma (NHL). Chemotherapy is a common therapeutic approach for the treatment of NHL and the chemotherapy combination consisting of cyclophosphamide, doxorubicin, oncovin, and prednisone plus the biologic agent Rituxan® (CHOP-R) is the standard of care for various types of NHL.

Results from previous clinical studies have indicated that CHOP-R administered on a schedule that is considered more dose-dense (given every 14 days) may be more effective for some patients than administering the regimen every 21 days. Delivery of dose-dense chemotherapy has been demonstrated in clinical trials to improve survival of patients with NHL and breast cancer. Dose-dense chemotherapy, however, is associated with a higher risk of some side effects. Specifically, dose-dense CHOP-R is associated with a higher risk of neutropenia.

Researchers from Europe conducted a clinical trial directly comparing Neulasta® to Neupogen® in patients with aggressive B-cell NHL. Patients were treated with CHOP-R every 14 days (CHOP-R 14) and received either an injection of Neulasta® once per chemotherapy cycle or daily injections with Neupogen®. The two groups were then directly compared. Planned cycles of chemotherapy could be administered to 98% of all patients who received Neulasta®, compared with 93% of all patients treated with Neupogen®. Of the cycles of chemotherapy administered, the rate of the planned dose of chemotherapy and administration on time was nearly identical between the two groups of patients (94% for Neupogen® and 94% for Neulasta®). Febrile neutropenia (neutropenia accompanied by fever) occurred in 1.4% of patients treated with Neupogen® and 3.9% of patients treated with Neulasta®.

The researchers concluded that the use of Neulasta® once per chemotherapy cycle of CHOP-R 14 is comparable to daily injections with Neupogen® in patients with aggressive B-cell NHL. Patients may wish to speak with their physician about their individual risks and benefits of using Neulasta® to facilitate the optimal delivery of chemotherapy and avoid the complication of neutropenia.(3)

Neulasta™ as Effective and More Convenient Than Neupogen® for Neutropenia

Neulasta is as effective and more convenient than Neupogen for the treatment of neutropenia caused by chemotherapy.

A multi-institutional clinical trial was conducted to directly compare Neupogen® to Neulasta™ in patients being treated with chemotherapy. This trial involved nearly 160 patients who were treated with the chemotherapy followed by either daily injections of Neupogen® or a one-time dose of Neulasta™.

The average duration of severe neutropenia, the average lowest white blood cell levels and the time it took for white blood cell levels to return to normal were the same regardless of treatment with Neupogen® or Neulasta™. However, neutropenia accompanied by a fever (febrile neutropenia) occurred in fewer patients treated with Neulasta™ (13%), compared to those treated with Neupogen® (20%). Neulasta™ was as safe and well tolerated as Neupogen®. (4)

A Single Dose of Neulasta® is as Effective as 16 Doses of Neupogen® in the Management of Patients with Leukemia

According to results recently presented at the 46th annual meeting of the American Society of Hematology (ASH), Neulasta® (pegfilgrastim) appears at least as effective as Neupogen® (filgrastim) in the treatment of chemotherapy-induced neutropenia in patients with acute myeloid leukemia. One injection of Neulasta® was comparable to 16 injections of Neupogen® in this group of patients.

Acute myeloid leukemia (AML) is a cancer of the bone marrow and blood characterized by the uncontrolled growth of immature white blood cells (immune cells), which never develop into functioning cells. Besides not being able to carry out the functions of mature immune cells, AML cells may also crowd out normal blood cells in the bone marrow and blood. AML is considered to be an aggressive cancer and patients are often at a high risk of developing a cancer recurrence following therapy, particularly if they are not able to undergo high doses of therapy.

Researchers have learned that the best way to cure patients with AML is to administer large doses of chemotherapeutic agents in a short period of time. The concept is to kill leukemia cells within 6 months before resistance to the drugs occurs. Therapy is divided into two phases: remission induction and post-remission consolidation/maintenance. Induction chemotherapy is administered to produce a complete remission in the bone marrow, which is defined as less than 5% “blasts” in the bone marrow sample and a return to normal blood counts. Patients are at a high risk for developing neutropenia during induction therapy. Neutropenia occurs when white blood cells (immune cells) are destroyed by chemotherapy, leaving the immune system unable to fight bacterial, viral and fungal infections. Chemotherapy-induced neutropenia is a serious condition for several reasons. Patients that develop neutropenia are more likely to get infections, may require hospitalization; and even minor infections can become life threatening. Perhaps more important and often overlooked is that patients who develop neutropenia often require a dose reduction or delay in their chemotherapy treatment, which may prevent patients from achieving the best possible outcome from chemotherapy treatment.

Researchers from Europe and Australia conducted a clinical trial to compare Neulasta® to Neupogen® in the treatment of chemotherapy-induced neutropenia in 83 patients with AML. Patients had undergone induction therapy with idarubicin and cytarabine and had developed severe neutropenia. Patients were then treated with either a single dose of Neulasta® or daily injections of Neupogen® for their severe neutropenia. The average time to recovery from severe neutropenia and the average duration of severe neutropenia was approximately 22 days in both groups of patients. Patients treated with Neulasta® only received one injection and patients treated with Neupogen® received an average of 16 injections. Complications associated with infections occurred in only 12% of patients treated with Neulasta®, compared with 22% of patients treated with Neupogen®.

The researchers concluded that Neulasta® appears at least as effective as Neupogen® and requires significantly fewer injections in treating chemotherapy-induced neutropenia in patients undergoing induction therapy for AML. Patients undergoing induction therapy with AML who have neutropenia may wish to discuss the risks and benefits of a treatment strategy utilizing Neulasta®.

References:

  1. Lyman GH, Kuderer MN, Crawford J, Dale DC. Prophylactic granulocyte colony-stimulating factor (G-CSF) in cancer patients receiving chemotherapy: a meta-analysis. Proceedings from the 17th MASCC/ISOO International Symposium. Geneva, Switzerland. 2005; Abstract #076-059.
  2. Kirshner JJ, Heckler CE, Janelsins MC, et al. Prevention of pegfilgrastim-induced bone pain: A phase III double-blind placebo-controlled randomized clinical trial of the University of Rochester Cancer Center Clinical Community Oncology Program Research Base. Journal of Clinical Oncology. 2012; 16: 1974-1979.
  3. Balducci L, Al-Halawario H, Charu V, et al. Elderly cancer patients receiving chemotherapy benefit from first-cycle pegfilgrastim. Oncologist. 2007;12:1416-1424.
  4. Lopez A, de Sevilla A, Castaigne S, et al. Pegfilgrastim supports delivery of CHOP-R chemotherapy administered every 14 days: a randomized phase II study. Proceedings from the 46th meeting of the American Society of Hematology (ASH). December 2004.
  5. Green M, Koelbl H, Baselga J. A randomized double-blind multicenter phase III study of fixed-dose single-administration pegfilgrastim versus daily filgrastim in patients receiving myelosuppressive chemotherapy. Annals of Oncology. 2003:14:29-35.
  6. Proceedings from the 2004 Multinational Association of Supportive Care in Cancer (MASCC) Annual Meeting. Schwarzberg L, et al. Abstract #A-52.
  7. Phase 3 Study Shows First-Cycle Administration of Neulasta Significantly Lowers Incidence of Infection and Hospitalization. Available at: . Accessed July 2004.
  8. Vogel C, et al. Phase 3 study shows majority of neutropenia with related fever and hospitalization occurs in first treatment cycle for breast cancer patients not receiving Neulasta®. Proceedings from the 27th annual San Antonio Breast Cancer Symposium. December 2004. Abstract #5044.
  9. Aapro M, Schwenkglenks M, Lyman G et al. Improved chemotherapy delivery in breast cancer patients receiving pegfilgrastim primary prophylaxis compared with current practice neutropenia management – results from an integrated analysis (NeuCuP). Presented at ECCO-14 – The European Cancer Conference. Barcelona, Spain, September 23-27, 2007. Abstract O#2033.
  10. Bosi A, Szer J, Kassis J, et al. A Multicentre, Double-Blind, Randomized, Phase 2 Trial Comparing Pegfilgrastim with Filgrastim as an Adjunct to Chemotherapy for Acute Myeloid Leukaemia (AML). Proceedings from the 46th annual meeting of the American Society of Hematology (ASH). December 2004. Abstract # 866.
  11. Lyman GH, Kuderer MN, Crawford J, Dale DC. Prophylactic granulocyte colony-stimulating factor (G-CSF) in cancer patients receiving chemotherapy: a meta-analysis. Proceedings from the 17th MASCC/ISOO International Symposium. Geneva, Switzerland. 2005; Abstract #076-059.

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