Low-dose chemo may keep cancer under control: study

A novel treatment strategy that uses lower amounts of chemotherapy may work better to keep cancer under control, rather than trying to wipe out tumours with powerful doses of medication, scientists say.
Despite numerous advances in oncology since the 'War on Cancer' began, many patients develop resistance to standard therapies and eventually relapse, researchers said.
Researchers at the Moffitt Cancer Centre in US hope to improve treatment outcomes with development of a therapeutic strategy, called adaptive therapy, which is based on evolutionary principals and aims to keep resistant cells in check by maintaining a population of chemo-sensitive cells.
Cancer drugs are given at the maximum tolerated dose that a patient can tolerate without any life-threatening toxicity.

While this strategy works very effectively at killing cancer cells in the short-term, once the chemo-sensitive cells are removed, existing chemo-resistant cells survive and then continue to grow and divide despite the ongoing therapy.
The adaptive strategy uses short bursts of therapy to maintain a residual population of chemo-sensitive cells that keep resistant cells in check and prevent them from growing uncontrollably.

"There is a natural tendency to use high-dose therapy based on the assumption that each patient receives maximum benefit by killing as many cancer cells as possible," said Robert Gatenby, study author and leader of the Cancer Biology and Evolution Programme at Moffitt.

"However, according to evolutionary principals, high-dose therapy is the least likely to be successful in controlling the tumour for any length of time because it intensely selects for resistant cells and allows them to grow rapidly because the treatment has eliminated all of their competitors," said Gatenby.
Researchers reported that adaptive therapy is effective in preclinical mouse models of triple-negative and Estrogen receptor-positive (ER+) breast cancer.
They treated mice with the common breast cancer chemotherapeutic agent paclitaxel according to three different treatment strategies: the standard maximum dose (ST), an adaptive therapeutic dose (AT-1) in which the frequency of paclitaxel is the same but the dose decreases as the tumour responds, and a second adaptive therapeutic dose (AT-2) in which the dose of paclitaxel is the same but doses are skipped when the tumour responds to therapy.

The researchers found that all three treatment strategies initially decreased tumour growth to similar levels; however, as soon as the tumours responded and treatment stopped during the standard regimen or was skipped during the AT-2 regimen, the tumours rapidly regrew.
Alternatively, treatment with the AT-1 dosing regimen resulted in a long-term stabilisation of the tumour to the point that lower doses of paclitaxel could be used and eventually treatment was able to be withdrawn completely.
Mice treated with the AT-1 regimen survived significantly longer than those in the standard and AT-2 treatment groups.
The research was published in the journal Science Translational Medicine.