Time to look closer at the ‘dark side’ of G-CSF

The indirect benefit of granulocyte-colony stimulating factor (G-CSF) in supporting patients on chemotherapy may be masking its ‘dark side’ – the potential to promote tumour progression and metastasis.

A review of the pre-clinical data on G-CSF provides strong evidence that the cytokine can stimulate tumour cell proliferation and promote angiogenesis.

G-CSF has also been implicated in the establishment and conditioning of the premetastatic niche in a second organ and in suppressing anti-tumorigenic immune cell populations.

However there is as yet no convincing evidence of it causing harm in the clinical setting and the known benefits outweigh currently unknown harms.

Associate Professor Andrew Redfern, from the Fiona Stanley Hospital and the Harry Perkins Institute of Medical Research, told the limbic there was incentive to look closer as G-CSF was being increasingly used.

“G-CSF is about to be substantially de-regulated. There are new PBS guidelines to use it for any cancer where cure or substantial remission is a target of the treatment and where there is a risk of moderate to significant neutropenia. So it is going to be used a lot more.”

“These are going to be scenarios where the benefit is less so we may be moving into a position where we are going to start giving it to people who will benefit less and there may be more potential harm in the future.”

The review found clinical evidence that G-CSF support offered a survival benefit in trials of acute lymphoblastic leukaemia and in metastatic, castrate resistant prostate cancer.

However the findings were not consistent with other trials, for example no survival benefit from G-CSF use in non-Hodgkin lymphoma.

“There is a benefit from using G-CSF in that you can use more chemo and you can get the dose intensity up to improve the cure rate. There is also the potential for a hidden deficit in there but it’s buried by the dose intensity advantage,” Associate Professor Redfern sai

The review also found evidence strongly linking G-CSF expression with poor survival in cohorts including patients with renal cell carcinoma, breast cancer, non-small cell lung cancer and other malignancies.

He said there was a need to start looking at the biology of cancers from the G-CSF perspective.

“It may be the people who are detrimented by G-CSF are those people with the G-CSF receptor.”

“There may be sub-groups where it is not a good idea even in standard usage and there may be potential for using G-CSF possibly with other non-myelosuppressive treatments to actually treat tumours by blocking it.”

“We may need to divorce G-CSF from chemotherapy and look at blocking it with anti-GCSF antibodies or anti-receptor antibodies and look for a benefit of targeting G-CSF alone.”

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