Doxorubicin administered weekly ...it can be done!3 Feb 2023 10:14
Pfizer's SmPC for doxorubicin 2 mg/ml Solution for Injection:
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"Administration of doxorubicin in a weekly regimen has been shown to be as effective as the 3-weekly regimen. The recommended dosage is 20mg/m² weekly, although, objective responses have been seen at 16mg/m². Weekly administration leads to a reduction in cardiotoxicity."
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https://www.medicines.org.uk/emc/product/6184/smpc
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"A Summary of Product Characteristic (or SmPC) is a monograph for medicines written and updated by pharmaceutical companies based on their product research and knowledge. It outlines important information about medicines such as form, clinical parameters and pharmacological properties."
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"SmPCs are checked and approved by the UK or European medicines licensing agency, ... [MHRA] and ... [EMA]. SmPCs are used by a range of healthcare professionals, including pharmacists, for prescribing and using medicine appropriately and safely."
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https://www.rpharms.com/development/trainee-pharmacists/product-characteristics-summary
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20mg/m² weekly is equivalent to the lowest standard dose of 60mg/m² in a 3-week cycle. (Highest standard dose is 75mg/m²)
If AVA6000 is causing mininimal side-effects and no cardiotoxicity at 200mg/m² (equivalent to 135mg/m² doxorubicin or 2¼ times the lowest standard dose) which, after three doses, is 600mg/m² total (equivalent to 405mg/m² doxorubicin), then...
How about changing the dosing regimen to 200mg/m² WEEKLY until (and allowing for prior anthracycline exposure) MTD is found?
4 weekly cycles would be a total of 540mg/m² doxorubicin equivalent,
5 cycles 675mg/m²,
6 cycles 810mg/m²,
7 cycles 945mg/m²,
8 cycles 1080mg/m²
and so on.
Even 150mg/m² weekly would quickly lead to multiples of the old maximum doxorubicin cumulative lifetime exposure and Phase 1a could be completed by the end of Q2 even with a very late start if, as we suspect, approval to change the dosing reginmen in the trial protocol is being sought - a process that is outside Avacta's and the SDMC's control and could take a long time.
Testing AVA6000 to breaking point or rapid evaluation of its potential, either way this would certainly move the clinical development along.
It depends on what the data and graphs show already and would show during such a rapid dose escalation of course.
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