Practice Update: Oncology

Drugs that boost white blood cells prove safe during

chemoradiotherapy of small-cell lung cancer

White blood cell-boosting drugs have proven safe during concurrent chemoradiotherapy of small-cell lung cancer, report late-

breaking results of a subanalysis of the phase 3 Concurrent ONce-daily VErsus twice-daily RadioTherapy (CONVERT) trial.

abio Gomes, MD, of the Christie

National Health Service Foundation

Trust, Manchester, UK, explained “Opti-

mal treatment for limited-stage small-cell

lung cancer is concurrent chemoradiother-

apy. The efficacy of this intensive treatment

is balanced by more toxicity, mainly hemato-

logical but also esophageal and pulmonary.

This is not a treatment for every patient and

many will struggle to stay on track with the

planned treatment.”

Granulocyte colony-stimulating factors are

commonly used supportively 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.

Its use during concurrent chemoradiother-

apy in small-cell lung cancer is controversial,

however, and the American Society of Clin-

ical Oncology (ASCO) recommends against

its routine use. The controversy is based on

results of a randomized trial of 215 patients

performed between 1989 and 1991. A signif-

icant increase in severe thrombocytopenia,

severe anemia, pulmonary complications,

and toxic deaths was observed when

granulocyte-macrophage colony-stimulat-

ing factors were used during concurrent

chemoradiotherapy.

Dr Gomes said, “Two major changes have

occurred since this trial was published in

1995 that may affect the safety of colo-

ny-stimulating factors in this context. First,

the trial evaluated granulocyte-macro-

phage colony-stimulating factors, which

act on more than one blood cell lineage

and are not used commonly.”

He continued, “Instead, we use granulo-

cyte colony-stimulating factors, which are

more specific and aim for neutrophil lin-

eage only. Second, modern radiotherapy

techniques have evolved significantly since

then, are more precise, and reduce the

risks of toxicity.”

CONVERT randomized 547 patients with

limited-stage small-cell lung cancer for

concurrent chemoradiotherapy to once-

or twice-daily radiotherapy. No difference

in overall survival was observed between

the two groups.

The protocol allowed the use of granulo-

cyte colony-stimulating factors, and around

40% of patients received one at some point

during the treatment. For the analysis pre-

sented at ELCC, toxicities and outcomes

were compared between patients who

received granulocyte colony-stimulating

factor during concurrent chemoradiother-

apy and those who did not.

They confirmed that the chance of severe

thrombocytopenia or anemia during treat-

ment nearly doubled in patients given

granulocyte colony-stimulating factor to

around 30% and 20%, respectively. These

incidences were lower than previous

reports.

Significantly higher use of further support-

ive measures such as platelet and blood

transfusions followed. No difference in the

incidence of pulmonary complications or

survival was observed.

Dr Gomes said, “Granulocyte colony-stimu-

lating factor exerted no significant negative

impact on patient outcomes, a comforting

result. Higher hematological toxicity was

balanced by appropriate supportive care

throughout treatment.”

He concluded, “The use of granulocyte

colony-stimulating factor during thoracic

radiotherapy is safe and supports the full

planned course of concurrent chemoradio-

therapy to achieve the best possible benefit.”

He added, “The findings should give clini-

cians the confidence to use granulocyte

colony-stimulating factor when needed in

this context. A complete analysis to be pub-

lished later this year may hopefully help

change current guidelines.”

Stefan Zimmermann, MD, of the Hôpi-

tal Cantonal, Fribourg, Switzerland,

said, “Oncologists need granulocyte

colony-stimulating factor to mitigate neutro-

penia and increase chemotherapy delivery

and compliance, but also want to see that

the benefits of timely concurrent therapy

outweigh the risks of toxicity.”

He concluded, “In this analysis, the use

of granulocyte colony-stimulating factor

did not raise risk of pneumonitis, but the

incidence of severe thrombocytopenia is

a concern. The use of granulocyte colo-

ny-stimulating factor was not detrimental to

progression-free or overall survival.

He continued, “We can conclude that pri-

mary or secondary prophylaxis of febrile

neutropenia with granulocyte colony-stim-

ulating factor is justified, but patients at

higher risk of thrombocytopenia should

be treated with caution.”

PracticeUpdate Editorial Team

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