A drug is said to be “experimental” if its efficacy is still uncertain and it is therefore available only in some specialized centers. In these centers, the drug is studied in accordance with specific research protocols that select the particular conditions of the patients to whom it can be administered. This means that an experimental drug cannot be given to all patients who ask for it.
While fairly few experimental therapies are available for use in the adjuvant phase (AN EXPERIMENTAL ADJUVANT THERAPY HAS BEEN PROPOSED), those aimed at the treatment of advanced cancer are very numerous.
When the patient is in an advanced stage of disease, taking part in an experiment is a possibility that should always be borne in mind. Indeed, given that the chances of curing advanced cancer are extremely slim, the gravity of the situation must take priority over all other considerations. If a center is experimenting with new drugs that have already yielded good results, participating in these experiments is a very good choice.
When there is a possibility of taking part in experimental clinical trials in the advanced stages of cancer, the practical problems that patients and their family members may face can be summarized as follows:
1. Is this experimentation suited to the patient’s condition?
Experimental trials usually have very strict entry requirements. For example, some trials are aimed only at patients who have not yet undergone any treatment for advanced cancer (experiments involving first-line therapies). Others are for patients who have already undergone unsuccessful first-line treatment. Moreover, within this requirement, the trial may only accept patients who have failed first-line therapy with the drug combination X Y.
This means that the patient may not be able to take part in a trial, even if she wants to, because she does not meet the “entry requirements”.
2.Is it a randomized study?
“Randomized” means that, once the patient has been accepted into the trial, the type of therapy is selected at random (… “at random?” Yes, at random!) from two possible therapies: a) the experimental therapy with the new drug; and b) the standard therapy (which is the therapy normally administered to such patients).
It is not easy to understand why patients are assigned randomly to receive one treatment or the other. In reality, however, this is the only scientifically valid way to prove that the new therapy is better than the old one; patient selection is left to chance. Indeed, if the doctors had to decide which patients should receive which therapy, they might (unconsciously) assign the new experimental therapy to those patients who are in the best condition, for example, and the standard therapy to those who are not in a worse condition. If that were to happen, the new therapy would probably yield better results than the old one – but only because those who received the new drug were in a better condition in the first place.
Randomization is very frustrating. The patient has a 50% chance of receiving the new drug, but he also has a 50% chance of participating in the trial without engaging in anything experimental. Nevertheless, there are two possible advantages of taking part in randomized experiments, even if the patient does not receive the experimental therapy.
- The possibility of “CROSSOVER”. In some experimental trials, patients who receive the standard therapy are allowed to switch to the experimental therapy if it becomes apparent that the standard therapy is no longer working. A patient who receives the standard therapy outside of the trial does not have this option.
- During the trial, the doctors may realize that the new therapy works better than the old one. In this case, a patient who has participated in the trial without receiving the new drug (i.e. he has received the standard drug) will be allowed to have the new drug before it becomes available to all; in other words, before it is approved and registered by the regulatory authorities (and these bureaucratic steps often take many months).
3.If the study is not randomized, is the experimental drug given to all the patients who take part?
In so-called phase-2 trials, the experimental drug is administered to all patients who participate. This would seem to be the best way conduct experimentation. In reality, however, there is a problem here, too; there is not yet enough certainty that the new drug works better than those already available, as the drug has not yet been tested on enough patients.
The aim of phase-2 trials is to determine the efficacy of a new treatment on a larger number of patients. Once this has been established, randomized trials are conducted in order to compare the new treatment with the standard treatments.
The advantage of taking part in a phase-2 trial is that all the patients receive the new drug; the disadvantage is that little evidence of the drug’s efficacy is so far available.
4.Are additional tests necessary in order to take part in an experimental trial?
The new biological, molecular targeted therapies can only work if there is a target to hit. It is therefore essential to find out whether there is a target or not. This is done by means of molecular tests on tumor samples. These tests can be carried out on a tumor that has been removed or biopsied in the past, but the most advanced experiments require new biopsies to be taken (THE BIOPSY USUALLY PROVIDES CERTAINTY). Taking new biopsy samples causes additional pain, discomfort and anxiety. It is important to discuss the issue openly with the doctor. In general, in well-organized studies involving very promising drugs, undergoing these extra procedures can really be worth it.
After reading all this information on the problems connected with clinical experimentation, we may be left with the impression that all these complications (additional biopsies, entry to the trial only on condition that this or that requirement is met, etc.) reflect a certain insensitivity on the part of doctors and researchers towards patients who are desperately searching for something that can improve their situation. This impression is false. Unfortunately, the clinical efficacy of a new treatment can only be demonstrated through rigorous trials. And, as yet, we have no better way to test new drugs