Now, a pill-a-day of a lung cancer drug may not be the required protocol to suppress regrowths
Cancer is a mass of cells gone rogue. They grow with little respect for boundaries and nutritional availability. Despite surgically removing a cancerous growth, some tumours recur after some time. Certain newer generation drugs targeted against mutated genes such as Erlotinib and Osimertinib are approved for lung cancer patients with mutations in what is known as the Epidermal Growth Factor Receptor, EGFR gene. Presently, these drugs are administered as daily doses in these cases as a pretreatment procedure. However, they are not without severe side effects. Therefore, any study that can justify reducing the drug dosage is highly desirable and an active research area.
A team of researchers from the Advanced Centre for Treatment, Research and Education in Cancer (ACTREC), Navi Mumbai, has investigated if a weekly dose of the drug, Osimertinib, could be as effective as a daily dose. They conducted experiments on the development of lung cancer in mouse models. Their study results published in Translational Oncology show that a weekly pretreatment dosage of Osimertinib achieves the same results as a daily dosage. This weekly dosage is perhaps as good or better than a daily dosage of Erlotinib in suppressing the tumours.
A recent ADAURA clinical trial has established the utility of a daily dose of Osimertinib as an adjuvant drug (a follow-up treatment given after surgical removal of the tumour) to reduce tumour relapse in patients and extend a disease-free survival for them. Currently, a daily dosage of the same drug can cost more than two lakhs per month. “Our study suggests a similar effect may be attained by weekly instead of daily dosing of Osimertinib, effectively reducing the cost by one-seventh,” says Dr Amit Dutt, head of the research team. Moreover, the reduced dosage could potentially lower the side effects of the medication; besides, administering a weekly dose is more manageable, he adds. A clinical trial to validate their finding is currently initiated at the Tata Memorial Hospital, Mumbai.
For their experiments, the team used a tail vein mouse model for lung cancers. In this approach, the cancer-inducing cells are injected into the animal through its tail vein. These cells then journey into the lungs of mice in 24 hours. Researchers tracked these cells in the animal’s lungs by using a luminescent protein marker that was genetically engineered into the cancer cells. These engineered cancer cells express an enzyme called luciferase, and the chemical reaction gives off luminescence or light. The glowing cancer cells indicate their current location and extent of spread.
The researchers worked with five groups of six mice each of the mouse models. Two groups were dosed daily, two weekly, and one was used as a control (not given any drugs). They pre-treated the mice with Erlotinib and Osimertinib as per the dosage protocol before injecting EGFR mutated human lung cancer cells. In this procedure called pretreatment, the drugs are given before the disease develops (here, before injecting the cancer cells) to mimic a post-surgical condition in humans. (In human trials, the drugs are prescribed after surgery).
(Image credits: authors of the paper)
The mice from each of the groups were injected with the tagged luminescent cancer cells and were monitored. The team observed that the control groups and some mice given Erlotinib showed the presence of lung cancer cells even after day one of injection. But none of the mice in the groups pretreated with Osminitrib on both daily and weekly regimens showed traces of the cancer cells in the lungs even after three days of being injected. Nor did they develop any tumours in the lungs even till the 30th day, implying that daily and weekly doses of Osminitrib yielded the same results.
The authors say that the efficacy of weekly dosage of Osimertinib over Erlotinib in clearing cancer cells from the lungs maybe because of the delayed metabolism of the drug, implying it will remain in the body for a longer time than quickly getting metabolised.
“This could likely be due to the longer-lasting action (half-life) of Osimertinib for 21 days compared to less than 24 hours for Erlotinib,'' says Dr Dutt.
It could also be due to maximum bioavailability (how much is circulated in the blood to reach the target site) of Osimertinib in tumour generation sites and the lungs. He adds that it also has a low clearance from the blood and high distribution in the human body.
Based on their observation, the researchers state that lung cancer pretreatment with Osimertinib daily or weekly doses may offer a viable treatment option to delay the onset of tumour recurrence in patients. The drug can be used as an adjuvant treatment after surgery of early-stage tumours.
Furthermore, cancer cells quickly become resistant to commonly used drugs. Therefore, a drug sparingly used (like in weekly dosages) is less likely to cause resistance. “Relapsed tumours, however, are often resistant to first-generation Erlotinib; thus, daily dosing of the same is not an option. Since our study suggests a weekly pretreatment with Osimertinib generating a response similar to its daily dosing, resistance could be delayed or prevented,” says Dr Dutt.
This article has been run past the researchers, whose work is covered, to ensure accuracy.