MedicalResearch.com Interview with:
Jonas Bergh M.D, Ph.D. F.R.C.P. (London, UK)
Professor of Oncology (Mimi Althainz´donation)
Director Strategic Research Program in Cancer
Radiumhemmet, Karolinska University Hospital
MedicalResearch.com: What is the background for this study?
Response: Present standard dosing of chemotherapy is aiming at a similar dose for each individual (similar effects and side-effects) , by calculating the dose per mg/m2 based on a formula originally established by du Bois (1916), based on body surface calculations by measuring height and weight. As I recall it, this was done on nine individuals…
However, the body surface has very little to do with how you cytotoxic drugs are metabolized and excreted… in practice this means that chemotherapy dosing based on body surface area will result in under- or overdosing of quite a proposition of the patients… Please Google/run a PubMed research on H. Gurney in Australia, he and other have really expressed their concerns with our present chemotherapy dosing strategies.
In our prospective adjuvant chemotherapy study of high risk breast cancer patients we tested a very well established standard chemotherapy regimen given every third week (FEC100 mg/m2 x 3+ docetaxel 100 mg/m2 x3) vs. our experimental arm given very second week in a dose dense fashion. We also tried to optimize the dosing, aiming at avoiding overdosing some patients at the first course and increase the dose for those without predefined toxicities. Therapy duration was similar in both groups, 15 weeks. Please see the end of the discussion in JAMA for the shortcomings with our study.
MedicalResearch.com: What are the main findings?
Response: The HR were in the same range (around a 17-23 % reduction of events) for all studied efficacy end-points (please see the abstract), albeit not statistically significant expect for the secondary end-point of event-free survival, the end-point with most events (and thereby having more power).
The toxicities were in general higher in the experimental group, please observe that those patients received two more courses and thereby having a higher chance to develop more toxicities. In addition, some of the toxicities should also be higher while patients in the tailored arm received higher cumulative doses of the drugs. On the good side; the higher doses did not result in a higher rate of secondary malignancies and the there was no increased risk of therapy related deaths, just one occurred in the standard group, overall demonstrating that modern adjuvant chemotherapy can be given safely.
MedicalResearch.com: What should readers take away from your report?
Response: Reflect around whether you can improve dosing of chemotherapy; present strategies based on body surface area dosing are by no means optimal. The present standard dosing strategy will result in too high doses for quite a few, resulting in marked toxicities; the starting doses should be considered be modified and for those tolerating the next course can then be given at higher dose levels, maybe being the regular starting dose.
MedicalResearch.com: What recommendations do you have for future research as a result of this study?
- Longer follow-up is important.
- To run exploratory studies aiming to understand more the biology in relation to the recorded effects and side-effects.
- The principles for tailoring should be explored by other investigators, aiming at reducing both under- and overtreament for used drugs.
MedicalResearch.com: Thank you for your contribution to the MedicalResearch.com community.
Foukakis T, von Minckwitz G, Bengtsson N, Brandberg Y, Wallberg B, Fornander T, Mlineritsch B, Schmatloch S, Singer CF, Steger G, Egle D, Karlsson E, Carlsson L, Loibl S, Untch M, Hellström M, Johansson H, Anderson H, Malmström P, Gnant M, Greil R, Möbus V, Bergh J, . Effect of Tailored Dose-Dense Chemotherapy vs Standard 3-Weekly Adjuvant Chemotherapy on Recurrence-Free Survival Among Women With High-Risk Early Breast CancerA Randomized Clinical Trial. JAMA.2016;316(18):1888-1896. doi:10.1001/jama.2016.15865
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