EXAMPLES OF CANCER HERBAL MEDICINE
There are examples of herbal medicines that have been tested in studies. One that I am particularly interested in is the mixture initially called PC-SPES (which stands for Prostate Cancer-spas, from ‘hope’ in Latin). This was allegedly produced from an ‘ancient’ Chinese herbal remedy, and marketed for ‘prostate health’. Around 20 years ago, it was apparent that patients in mainline prostate cancer trials who happened also to be taking PC-SPES were deriving benefit from the herbal remedy. Despite its name, it was never tested by its makers as a cancer therapy but was licensed as a food supplement. Subsequent laboratory investigation confirmed that PC-SPES behaved like an oestrogen – technically, a phyto- (meaning plant) oestrogen. It will be recalled that oestrogens are widely used in prostate cancer therapy, and thus it is entirely plausible that PC-SPES would have anti-prostate-cancer effects. Detailed study of patients, taking the mix demonstrated effects on male hormone levels and the prostate cancer marker PSA consistent with a hormonal basis for action. The clinical and chemical analyses were published in the New England Journal of Medicine, probably the world’s premier medical journal.
This publication prompted the setting up of a trial comparing PC-SPES with a real oestrogen called stilboestrol in patients with advanced prostate cancer. The trial commenced but was stopped early due to minute levels of contamination of PC-SPES with stilboestrol. Botanic Laboratories, the manufacturers, were then shut down by the regulatory authorities in the USA, ending any possibility of completing the study. There are puzzling aspects to this story. PC-SPES had been made for years with no adverse inspections, and analysis in the original New England Journal article had found no contamination with stilboestrol. Furthermore, the trial, in so far as it was completed, suggested that PC-SPES was superior to stilboestrol, a result incompatible with the clinical effects being due to stilboestrol contamination, as has been suggested by some commentators.
The problem with agents such as PC-SPES is that they are only licensed as foodstuffs and hence not subject to the sorts of evaluations that a drug will have to go through. Also, the preparation is a mixture of herbal extracts, raising the question of how many components of the mix are actually required for the undoubted clinical effects seen (which included some of the known adverse effects of oestrogens such as deep vein thrombosis). The example of Shropshire tea and digoxin illustrates the potential route of development. Unravelling this would, of course, take many years and many healthcare dollars, possibly with no patent protection to allow the company to fund these costs. We will probably therefore never know what the real active ingredients are in PC-SPES. Furthermore, although the agent looked to have clinical value, it is no longer available, though a number of similar agents (called by various names, including, in a direct reference to PC-SPES, PC-HOPE) have appeared on the market and are widely used by patients. Whether these PC-SPES clones are really the same as the original, again, we will never know. With patients taking these largely unsupervised, there is no consistent body of literature on dosing, adverse effects, and so on. In addition, as these are mixtures of herbs, even if the components by weight are the same, there is no guarantee that the actual active components will be the same in consecutive batches – anyone who has a garden will know the variation seen from year to year in the plants they grow in the same bit of ground. It is hard to see any coherent way forward given the nature of herbal remedies and the current licensing environment. Companies are unlikely to queue up to carry out trials in the future of their herbal remedies given what happened to Botanic Labs with PC-SPES. Equally, the costs of turning a herbal mix into a regular drug with potentially no patent protection seem prohibitive. The pharmaceutical industry will, of course, continue to screen herbs for useful drug properties, but the subsequent development will be aimed at a single chemical entity not a herbal brew. I suspect that these agents will be forever in a shadowy hinterland between conventional medicine and alternative practitioners. This is unfortunate, as mixed in with the large numbers of ineffective therapies such as mistletoe extracts, there will undoubtedly be agents with potentially valuable activity such as PC-SPES.
In conclusion, complementary and alternative medicines form a large and economically important activity in the health economy. However, direct evidence of benefit for most such therapies is hard to find. Furthermore, in some cases, there is good evidence of lack of benefit. Despite this, a large proportion of cancer patients use these treatments as adjuncts to (or in some cases, in place of) their conventional therapies. Alongside these quasi-medical interventions, there is a further arena of altered diets, supplements, and herbal remedies, again largely with little or no evidence base. Understanding usage of these treatments is important as they may confound the results of trials in cancer therapy and also may interfere with outcomes from conventional therapy, either for better (rarely, probably) or for worse.