EAPC - ipac

414 EAPC Abstracts
Objective: To identify and discuss the clinical components of best supportive
care (BSC) packages for patients in lung cancer trials and to determine
to what extent the conduct of clinical and cost-effectiveness analyses
(CEAs) are fully informed. Design: Systematic review of RCTs, systematic
literature reviews (SRs) and economic evaluations (EEs) which compare
chemotherapy versus BSC for adult patients in lung cancer trials. Results:
26 RCTs, 13 SRs and 41 EEs met the review inclusion criteria. Less than
50% of relevant studies included formal definitions of BSC. None of the
papers included in the review adequately described or outlined the BSC
options available to patients, how BSC was delivered or by whom. Data
described in the studies do not facilitate the generation of a clear definition
of a patient pathway in relation to BSC or a clear list of components or costs
of such care. Conclusions: Failure to clearly define BSC packages means
that comparison of treatment outcomes within and across trials is problematic.
Formal definitions of BSC with set parameters for the common complications
of advancing disease, not just the physical symptoms, need to be
established to inform the design of future RCTs and CEAs. From an ethical
perspective, it would seem appropriate to provide patients with an adequate
definition of the care they could expect to receive within the comparator
arm of a cancer trial. Health care professionals involved in the conduct and
reporting of cancer trials must aim to communicate the BSC package delivered
to patients.
49 Invited Lecture
Best Supportive Care versus chemotherapy The right question
to ask
Optimal outcomes for studies comparing best supportive care
with chemotherapy
Authors: Fausto Roila Medical Oncology Division ITALY
Sonia Fatigoni Medical Oncology Division Perugia ITALY
Until 10 – 15 years ago chemotherapeutic agents have been introduced in
the clinical practice on the base of their activity represented by the rates of
complete and, more frequently, partial responses, their duration and the
time to the disease progression. On the other hand, these variables did not
necessarily have a clear relationship to the treatment’s impact on survival
and quality of life, that represent the indexes of efficacy. Therefore, many
subsequent phase III studies in several disseminated cancer patients compared
the chemotherapeutic agents with respect to the best supportive care
to demonstrate their efficacy. Even not clearly defined and standardized,
best supportive therapy means the best control of the cancer symptoms in
the clinical practice. Today, we have several of these studies carried out for
example in lung, gastric, pancreatic disseminated cancer that often showed
the superiority of the chemotherapeutic agents or combinations in terms of
overall median survival without a negative impact on the quality of life. Of
course, these studies should have been planned with a sound methodology
(i.e., randomized, prospective, if possible blind studies with a sample size
calculation, using validated quality of life instruments, etc.).
Unfortunately, until recently, this has not been the case for many of these
studies as we will discuss in the presentation. Furthermore, it is necessary
to outline that these studies in any case need to be well interpreted. For
example, the frequent impossibility to blind the treatments even if have not
impact on survival conditioned their effect on quality of life (symptoms
and adverse effects, psychological status, social relationship, etc). This is
also true for double blind, placebo-controlled, phase III studies evaluating
the efficacy and tolerability of target therapies in which adverse events
(i.e., skin toxicity) permit to recognize patients submitted to the treatment
with respect to those submitted to placebo. Finally, the administration of
large doses of corticosteroids for more consecutive days to avoid adverse
events of chemotherapeutic agents, as in the case of docetaxel, could
induce a better quality of life with respect to patients receiving best
supportive care alone due to impact of corticosteroids on symptoms (amelioration
of anorexia, asthenia, nausea and cenestesis). In this case we
erroneously could have attributed this result on quality of life to the
chemotherapeutic agents.
50 Invited Lecture
Best Supportive Care versus chemotherapy The right question
to ask
BSC a faulted methodology in need of standards
Authors: Nathan Cherny Shaare Zedek Medical Center Director Cancer
Pain and Palliative Medicine, Dept Oncology ISRAEL
(BSC) in two 1988 articles reporting on chemotherapy studies initiated in
1983–84. The qualifier “best” implies that patients are provided optimal
palliative care. Most studies which employ a best supportive care arm
enroll patients with poorly responsive cancers such as non-small cell lung
cancer and colorectal cancer. Usually, but not invariably, the supportive
care arm is found to be inferior to the chemotherapy arm with respect to
objective tumor response and survival. It was subsequently concluded that
it is almost always better to receive treatment than to be referred for palliative
care. This literature is intrinsically misleading since the term “BSC”
does not represent any formally defined concept, rather, it evolved as a
politically correct alternative to “no chemotherapy” that would be palatable
to both patients and ethical review boards. In actuality the “BSC” provided
in these studies can, at best be described as ad-hoc provision of supportive/palliative
care by oncology physicians with no specific training.
Indeed, one may suspect that in some studies the so-called “best supportive
care” may more accurately be expressed as “not-so-best supportive
care”. This suggestion is supported by a very well developed literature
indicating that many oncologists have deficient skills in the management
of pain and palliative care. This adds further to the doubt that in the
absence of highly specified programs involving palliative care physicians,
patients would have received “BSC”. The methodologies in these studies
are characterized by a paucity of data describing “BSC”. Overall the treatment
programs were reactive i.e. that people can receive antibiotics for
infection, opioids for pain, blood transfusions for anemia, etc. Not one
investigator involved a palliative care or hospice team in a study. It is thus
impossible to draw conclusions at to the relative merit of skilled palliative
care as compared to chemotherapy for this patient group. This analysis
underscores the need for clear standards for the “BSC” arm of clinical studies
seeking to address this important question.
51 Invited Lecture
The Trial of Trials in Palliative Care Research
Choosing a placebo
Authors: Claudia Bausewein Dept. of Palliative Care, Policy &
Rehabilitation Kings’s College London UNITED KINGDOM
Randomised controlled trials (RCTs) aim to establish the efficacy of a new
intervention. If there is no active or standard beneficial treatment placebos
are often used as controls. A placebo is defined as a substance without a
pharmacological effect or a sham treatment or an inactive procedure. The
so-called placebo effect is a non-specific effect related to the credibility of
the intervention, patients’ expectations and the therapeutic setting. There is
controversy about the size of the placebo effect. It has been questioned
whether there is an effect at all. Mostly it has been estimated to be about
30% but beneficial results of up to 60–90% have been reported. However,
the claimed effects may be due to spontaneous improvement, fluctuation of
symptoms, regression to the mean, additional treatment, answers of politeness,
scaling bias etc. Careful attention has to be given to which placebo to
choose. This might be straight forward in a drug trial. Originally, RCTs
focused on drugs with a bio-medical theory base. A drug is prescribed on
the base of a bio-medical diagnosis which has been established beforehand.
In these pharmacological trials inert dummy pills are frequently used as
placebos. However, more recently complex interventions such as acupuncture
or psychotherapy or multi-professional palliative care interventions
are also tested in RCTs. Often complex interventions such as acupuncture
have a non-biomedical theory base where talking and listening to patients
are part of the intervention. In trials with experience-based treatments it is