Clinical trial design for research into cancer in the elderly

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Published: 30 Mar 2011
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Prof Antonio Cherubini - Perugia University Medical School, Italy and Prof Lodovico Balducci - Moffitt Cancer Centre, Tampa, Florida, USA
Prof Antonio Cherubini and Prof Lodovico Balducci speak about the importance of trial design in the research of elderly haematological cancer patients. In order to develop improved therapies for these patients we must increase their representation in clinical trials. The majority of elderly cancer patients are not eligible for randomised clinical trials due to comorbidities or other problems. Profs Cherubini and Balducci stress the need for increased collaboration between haematology oncologists and geriatricians and discuss ‘evidence biased trials’; where large scale international databases that include all patients are used in order to identify problems that are significant to cancer development.

Blood Cancer in the Elderly: European Expert Forum, Rome, 19—20 March 2011

Professor Antonio Cherubini (Perugia University Medical School, Italy) and Professor Lodovico Balducci (Moffitt Cancer Centre, Tampa, Florida, USA)

Clinical trial design for research into cancer in the elderly 

Interviewed by Peter Goodwin

PG: This is reporting from Rome and the Blood Cancer in the Elderly European Expert Forum. Antonio Cherubini, you’re from Italy and also Lodovico Balducci, you were from Italy but now you’re from Tampa, Florida. Now, Antonio, you’re primarily a gerontologist and Lodovico, you’re primarily an oncologist but you came together in this session on managing elderly oncology patients. What do you think are the key things that came out of your discussions in this morning’s session here in Rome?

LB: One of the key issues that came out is, first of all, that we need to identify the best trial design to answer the proper questions in cancer in the elderly. Because the aged population is a very diverse population and it is virtually impossible to account for all the variables that are present in randomised clinical trials.

PG: Antonio, how is that done then?

AC: I presented a European project funded under FP7 called Predicta that addresses the issues concerning exclusion of older people from clinical trials. So there is no doubt that we need to push for including these older people in clinical trials from the early phase to the late phase to understand better what drugs or other treatments can do in this population. But, of course, it is important also to organise large scale databases, that are adequately powered in terms of data, with a collaboration between oncologists and geriatricians to answer questions that clinical trials will never be able to answer.

PG: Yes indeed, co-operation has been a real key issue discussed here in Rome. How do you think this should be done? In fact, do you think geriatricians should be more heavily involved in therapy for patients who are older?

AC: I think we should change the current situation in which there is very little collaboration between haematologists and geriatricians and we should work together, integrating. We need screening and then after the screening we need to identify patients who need the comprehensive geriatric assessment by geriatricians and then we need to work closer with the haematologists and the oncologists that are going to treat this patient and to co-operate for the long-term management.

LB: I agree completely with what Antonio said. From an oncological standpoint what I would like to see happen is that the geriatricians were the primary care physician for an older patient. The geriatrician would be responsible therefore to evaluate the patient - to see what the patient’s life expectancy is in each situation; to see what the patient’s tolerance of stress is, which means tolerance of cancer treatment; to identify the weaknesses of the patient which may cause disability at a later time. For example, I had an uncle of my wife who was one of the most prominent anaesthesiologists in Italy. At age 80 he was still doing snow skiing, down-slope skiing, until he developed colon cancer. A very small colon cancer, he was operated. When he recovered from the operation he started folic and from then on he has been in a completely down-slope situation. Right now he’s practically completely dependent. Was it possible to identify this patient before and prevent him from losing this functional capacity? So that would be one of the keys of the geriatrician’s work in the management of these patients.

PG:  One of the ways of doing that would be randomised controlled trials, but I think you have referred to evidence biased medicine?

LB: Yes. Unfortunately I cannot take credit of that, I think Dr Grimley Evans from the United Kingdom said that in geriatrics, evidence based medicine is evidence biased medicine. The reason is because the randomised clinical trials are very important, like Antonio said, to answer some specific questions. For example, a randomised controlled trial was very important to establish that chronologic age was not a contra-indication to tolerate the treatment for lymphoma. But randomised controlled trials exclude the majority of the patients on account of their comorbidity, of their poor function, of a lot of other problems that are the most common problems in the elderly. So they don’t tell us what happens on the field, they only tell us what happens in the laboratory of the randomised clinical trials.

PG: How, though, do you study cancer in older patients?

LB: As Antonio said, you need to have some very wide, worldwide or at least nationwide, databases in which all older patients are evaluated in the same way in terms of function, in terms of comorbidity, in terms of social support. And after you’ve studied hundreds and thousands of these patients, you realise what factors are important.

PG: But we want to convert cancer to becoming less of an enemy. At the moment it’s shaping up to be a really big enemy.

AC: Exactly, because we have found ways to fight very efficiently cardiovascular diseases and stroke and there are studies showing in the last thirty years that we gained almost five years of life expectancy by defeating these diseases. But unfortunately it’s not the case for cancer and the people that now live longer, surviving a myocardial infarction or a stroke, they will develop a cancer in the future. So cancer is becoming more and more diffuse and still not very treatable in the elderly.

PG: What are your suggestions?

AC: That we need to concentrate our efforts in order to find, not only new therapies, but also new management pathways for these patients.

PG: Now the two of you are absolutely agreed on co-operating the different disciplines. What’s the formula for getting that right?

LB: Well I would say France is an excellent example because France, in geriatric oncology, has already realised that the geriatrician and the oncologist work together virtually in the evaluation and the follow-up of every older patient with cancer. That is the way to do it, simply to make sure that every patient aged 70 and older has a trained geriatrician as a primary care physician and this trained geriatrician is responsible to co-ordinate all the choices related to the health of this patient.

PG: So could I ask both of you, finally, to sum up what are your hot tips for the busy clinician about how best to manage hematologic malignancy in older patients?

LB: Assuming that this co-operation between geriatrician and oncologist does not exist yet, I think that an oncologist needs at least to be able to realise whether the older patient is functionally independent, that is whether the older patient is able to survive alone. Second, is independence of so-called instrumental activity of living, second to make sure what kind of comorbidities the patient has and in particular rule out cardiovascular, pulmonary, renal and other cancer comorbidities. Third, make sure the patient is getting the right medications.

AC: I think, yes, we need to increase the awareness and the knowledge of the haematologist about geriatric issues and geriatricians about haematological issues. So the complexity of older patients does not really allow short-cuts. We need to improve the qualification of both specialties and to start to work together. There was this morning also the excellent proposal of a formal evaluation of the efficacy of adding the comprehensive geriatric assessment to the usual management of onco-haematological malignancies and I think that this is the way forward.

PG: Professor Antonio Cherubini and Professor Lodovico Balducci, thank you very much indeed for joining me here on