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ELCC 2017: Study Shows White Blood Cell–Boosting Drugs Safe During Small Cell Lung Cancer Chemoradiotherapy

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Key Points

  • The chance of severe thrombocytopenia or anemia during treatment almost doubled in patients given G-CSF to around 30% and 20%, respectively—however, these were lower than previously reported.
  • The development of hematologic toxicities was followed by a significantly higher use of further supportive measures, such as platelets and blood transfusions.
  • There was no difference in the incidence of pulmonary complications or in survival.

A late-breaking subanalysis of the phase III CONVERT trial presented by Gomes et al at the 2017 European Lung Cancer Conference (ELCC) shows that white blood cell–boosting drugs are safe during concurrent chemoradiotherapy of small cell lung cancer (SCLC, Abstract LBA2_PR).

“The optimal treatment for limited-stage SCLC is concurrent chemoradiotherapy,” said lead author Fabio Gomes, MD, a medical oncologist at the Christie NHS Foundation Trust, Manchester, UK. “The efficacy of this intensive treatment is balanced by more toxicity, mainly hematologic but also esophageal and pulmonary … meaning this is not a treatment to be considered for every patient, and many more will struggle to stay on track with the planned treatment”.

Controversial Usage

Granulocyte colony-stimulating factors (G-CSFs) are commonly used as a supportive measure to boost the survival, proliferation, and differentiation of neutrophils. The expected neutropenia is less severe, and patients recover more quickly, reducing their risk for infectious complications. However, its use during concurrent chemoradiotherapy in SCLC is controversial—ASCO recommends against its routine use, according to research published by Smith et al in the Journal of Clinical Oncology. This is due to a randomized trial published by Bunn et al in the Journal of Clinical Oncology with 215 eligible patients treated between 1989 and 1991, which showed a significant increase in severe thrombocytopenia, severe anemia, pulmonary complications, and toxic deaths when granulocyte-macrophage colony-stimulating factors (GM-CSFs) were used during concurrent chemoradiotherapy.

Dr. Gomes said, “There have been two major changes since this trial was published in 1995 that may affect the safety of CSF in this context. First, the trial tested GM-CSFs which act on more than one blood cell lineage and are not commonly used nowadays. Instead, we use G-CSFs, which are more specific and aim for the neutrophil lineage only. Second, modern radiotherapy techniques have evolved significantly since then and are more precise, which reduces the risks of toxicity.”

CONVERT Trial Findings

The phase III CONVERT trial enrolled 547 patients with limited-stage SCLC for concurrent chemoradiotherapy who were randomized to once-daily or twice-daily radiotherapy. There was no difference in overall survival between the two groups.

The trial protocol allowed the use of G-CSF, and around 40% of patients received it at some point during the treatment. For the analysis presented, the researchers compared the toxicities and outcomes between patients who received G-CSF during concurrent chemoradiotherapy and those who did not.

They confirmed that the chance of severe thrombocytopenia or anemia during treatment almost doubled in patients given G-CSF to around 30% and 20%, respectively—however, these were lower than previously reported. That was followed by a significantly higher use of further supportive measures, such as platelets and blood transfusions. However, there was no difference in the incidence of pulmonary complications or in survival.

Dr. Gomes said, “G-CSF had no significant negative impact on the outcomes of these patients, which is a very comforting result. The higher hematologic toxicity was balanced by an appropriate supportive care throughout treatment.”

He continued, “We can conclude from this analysis that the use of G-CSF during thoracic radiotherapy is safe and should support patients to receive the full planned course of concurrent chemoradiotherapy and achieve the best possible benefit. These findings should give clinicians the confidence to use G-CSF when needed in this context. We aim to publish a complete analysis later this year, which may hopefully help change the current guidelines.”

Commentary

Commenting on the findings, Stefan Zimmermann, MD, Senior Consultant, Medical Oncology Department, HFR–Hôpital Cantonal, Fribourg, Switzerland, said, “Oncologists do need G-CSF to mitigate neutropenia and increase chemotherapy delivery and compliance, but want the beneficial effect of timely concurrent therapy to outweigh the toxic risks.”

“In this analysis, the use of G-CSF did not result in an increased risk of pneumonitis, but the incidence of severe thrombocytopenia is a concern,” he continued. “The use of G-CSF was not detrimental to progression-free survival or overall survival. We can conclude that primary or secondary prophylaxis of febrile neutropenia with G-CSF is justified, but patients at higher risk for thrombocytopenia should be treated with caution.”

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.


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