15-07-2025
The Global Applicability of Oral Metronomic Chemotherapy
This transcript has been edited for clarity.
Hello. I'm David Kerr, professor of cancer medicine at University of Oxford. Today, I'd like to discuss a really interesting paper published in JCO Global Oncology by an outstanding cooperative Indian group that was led by Akhil Kapoor. They were interested in looking at platinum-refractory advanced head and neck cancer.
We know that it has a terribly poor outcome with very limited treatment options. Remember, if we're looking at low- and middle-income countries, access to immune checkpoint inhibitors is difficult, given the relative expense of these drugs.
They performed a randomized clinical trial, I think rather beautifully, and I think this is a trial which will be very impactful, perhaps predominantly in low- and middle-income countries, although it would definitely be applicable in some salvage settings in the north and in the west.
They randomized against triple oral metronomic chemotherapy, so this is low-dose continuous chemotherapy. The theoretical basis for this, which we've discussed many times before, is a means of delivering a combination of treatment relatively safely — more on the combination in a moment.
They evaluated triple oral metronomic chemotherapy, which is deliverable in a large complex country such as India with [a large rural poor population], and that was randomized against chemotherapy of physicians' discretion. They randomized 214 patients using a conventional 11-to-11 [ratio]. The metronomic chemotherapy was erlotinib, celecoxib, and methotrexate, given in a low dose weekly.
For physician-determined treatment, the dominant drugs used were capecitabine and gemcitabine, but paclitaxel and docetaxel were used also. Both arms were very well balanced in terms of demographic and prognostic factors, and more than 95% of patients in each arm received the chemotherapy that was promised.
They demonstrated that overall survival, the primary endpoint of the study, was 5 months in the oral metronomic chemotherapy arm compared to 3.1 months in the physician-selected, conventional salvage chemotherapy arm, with a hazard ratio of 0.63 and a very high P value.
I think this is a really important piece of work. Importantly, overall survival counts. Nevertheless, the metronomic chemotherapy improved global health status, physical function, fatigue, and insomnia, and it was well tolerated, with fewer grade 3 or higher adverse events — 28% vs 40% compared to conventional salvage chemotherapy.
This is an important randomized trial. There are many phase 2 trials of metronomic chemotherapy, but this is a cooperative group with a number of important Indian leaders in the field who designed and delivered a trial, which I think will be impactful throughout the world.
The doses and the relative safety of the oral metronomic chemotherapy mean that it can be delivered potentially in district hospitals rather than in fully well-established, central, large cancer centers, and given its relative safety, delivered with a relatively light touch in terms of the blood tests required and so on.
It's a really nice piece of work. Have a look at it and see what you think. As I say, I think this is a message not just for low- and middle-income countries, but as a potential salvage therapy in those countries that are relatively more affluent. Congratulations to the team on this piece of work.
