Posted: Oct 24, 2016 10:11 pm
by Weaver
Cast an overly wide net, you'll gather in together overly broad conclusions. In this case, mixing in the best chemotherapies with the worst, and cherry-picking only the 5-year survival index - eliminating, say, 2-year for particularly invasive, aggressive cancers which do a lot of damage before they're stopped, and not dealing with the fact that most cancer detections are in the elderly who already have reduced lifespans simply due to age.

There are many other large studies which show highly positive benefits from chemotherapies:

https://www.sciencebasedmedicine.org/ch ... m-history/ (an excellent primer on chemotherapies)

Chemotherapy and breast cancer

There’s one study that I like to cite to people who claim that chemotherapy doesn’t work, and this post seems as good a place to do it as any. It’s a large meta-analysis from two years ago. Funded by Cancer Research UK, the British Heart Foundation and the UK Medical Research Council, this study was carried out by the Early Breast Cancer Trialists’ Collaborative Group (EBCTCG) at the Clinical Trial Service Unit at the University of Oxford, United Kingdom and entitled “Comparisons between different polychemotherapy regimens for early breast cancer: meta-analyses of long-term outcome among 100,000 women in 123 randomised trials.”

It’s really quite an incredible effort to collate patient-level data for so many women in so many clinical trials. I sometimes say about meta-analyses the prototypical complaint about meta-analyses, namely that the quality of the output is critically dependent on the quality of the input. In other words, “garbage in, garbage out.” However, the inclusion criteria for the EBCTCG are actually pretty stringent. More importantly, the EBCTCG has access to unpublished data and patient-level information, as is explained here. The EBCTCG also goes to great lengths to try to include data from every randomized trial ever published, or an unbiased subset of them, in order to try to minimize selection bias that all-too-often results from too-rigid selection criteria used for meta-analyses. All in all, it’s an enormous effort.

Overall, this meta-analysis involved over 100,000 patients involved in 123 randomized trials over 40 years, and the authors made these comparisons: (1) taxane-based versus non-taxane-based regimens (data for 33 trials, begun in 1994-2003); (2) any anthracycline-based regimen versus standard or near-standard (cyclophosphamide/methotrexate/5-fluorouracil (CMF, 20 trials, begun in 1978-97); (3) higher versus lower anthracycline dosage (six trials, begun in 1985-94); and (4) polychemotherapy versus no adjuvant chemotherapy (64 trials, begun in 1973-96, including 22 of various anthracycline-based regimens and 12 of standard or near-standard CMF). Several meta-analyses were performed, which produced five main findings:

Standard CMF and standard 4AC (ACT without the “T,” which is an older chemotherapy regimen used before taxanes were developed) were roughly equivalent in efficacy. Both of them roughly halved two-year recurrence rates and resulted in a proportional decrease in recurrence over the next eight years by approximately one-third. Overall, breast cancer mortality rates were reduced proportionally by 20-25%.
Regimens with lower chemotherapy doses per cycle were less effective.
Regimens with a lot more chemotherapy than the old standard 4AC (but not so nasty that they required stem-cell rescue) were somewhat more effective. They further decreased breast cancer mortality by 15-20%. The most prominent of these regimens is 4AC plus four cycles of “T” (a taxane), which became the standard of care for node-positive breast cancer after taxanes were developed.
In all chemotherapy comparisons, the ten year overall mortality was reduced because there was not very much excess mortality due to causes other than breast cancer during the first year.
In all meta-analyses looking at taxane-based regimens or anthracycline-based regimens (doxorubicin is an anthracycline), the proportional reductions in early recurrence, any recurrence, and breast cancer mortality were more or less independent of age, nodal status, tumor size, or even estrogen receptor status.
The authors conclude:

While awaiting the results of these new trials, it appears that ER status, differentiation, and the other tumour characteristics available for the present meta-analyses had little effect on the proportional risk reductions with taxane-based or anthracycline-based regimens. The more effective of these regimens offer on average a one-third reduction in 10-year breast cancer mortality, roughly independently of the available characteristics. The absolute gain from a one-third breast cancer mortality reduction depends, however, on the absolute risks without chemotherapy (which, for ER-positive disease, are the risks remaining with appropriate endocrine therapy). Although nodal status and tumour diameter and differentiation are of little relevance to the proportional risk reductions produced by such chemotherapy (and by tamoxifen therapy), they can help in treatment decisions as they are strongly predictive of the absolute risk without chemotherapy, and hence of the absolute benefit that would be obtained by a one-third reduction in that risk.