| Anticancer chemotherapy is one of the rare fields of therapeutics
in which, with the exception of haematology, most treatment has historically
been given intravenously. Until recently few of the available drugs were
suitable for oral administration, and, therefore, most treatment has
been administered only by specialist staff.
In the past two years several new oral anti-cancer agents have become
commercially available and many more are in development. For example,
it has been estimated that in 2002 alone over 4,000 patients were treated
with capecitabine and by 2005 it is likely that tens of thousands of
outpatients will be receiving oral anti-cancer treatment of some kind.
Oral anti-cancer treatment may offer advantages to patients and to the
NHS. It does not necessitate admission or direct supervision and places
a lesser burden on pharmacy and nursing staff in overstretched chemotherapy
reconstitution and day units. For pharmacy, although there may be a considerable
reduction in the workload for the chemotherapy reconstitution unit, a
significant burden may be shifted to dispensaries and to less specialised
staff. To manage this transition safely and efficiently, thorough planning
will be needed. Treating patients with oral drugs challenges the traditional
approach to anti-cancer treatment, particularly the use of potent anti-cancer
chemotherapy drugs, which have a narrow therapeutic index. Home-based
treatment may continue for weeks at a time without direct professional
intervention or supervision. The significance of, and reasons for, intermittent,
pulsed treatment may be hard for some patients to grasp, yet misinterpretation
carries the risk of serious harm. Education of primary care professionals
and patients about the use and potential for misuse of oral chemotherapy
will be critical to patient safety.1
Compliance with treatment is relatively easy to achieve when professionals
administer treatment personally. When the responsibility for administration
is shifted to the patient, safe and effective treatment requires concordance
rather than, simply, compliance. Cancer patients are often thought of
as well motivated to comply with their treatment instructions. In a study
of patients with lymphoma, Lee et al2 found 100 per cent overall compliance
for oral medicines. In a study of breast cancer patients however, Lebovitz
et al3 found that only 43 per cent took their oral cyclophosphamide as
prescribed and some exceeded the prescribed dose. Experience with capecitabine
has shown the importance of ensuring that patients recognise side effects
so that treatment can be modified accordingly.1
Definitions
For the purposes of this document the term “oral anticancer drugs” is
used to refer to all drugs with direct anti-tumour activity, orally administered
to cancer patients, including: · Bexarotene, busulphan, capecitabine, chlorambucil, cyclophosphamide,
estramustine, fludarabine, hydroxyurea, idarubicin, melphalan, methotrexate,
procarbazine, tegafur/uracil, tioguanide. Oral vinorelbine is likely
to be licensed in 2004.
· Partially targeted treatments such as imatinib and gefitinib.
· Other drugs such as thalidomide.
· Pulsed, intermittent treatments where oral administration replaces
parenteral administration in cyclical regimens; chronic maintenance therapies.
It does not include hormonal or anti-hormonal agents.
It would be inappropriate for BOPA to make firm recommendations about
non-oncology practice. We recognise, however, that many cytotoxic agents
and other potentially hazardous drugs are used in other specialties.
We urge oncology pharmacists to draw these guidelines to the attention
of relevant colleagues and to encourage them to apply the principles
to their own areas of practice.
Principles of safe practice
· The principles of the chemotherapy standards in the Manual of Cancer
Standards (or the equivalent for Wales and Scotland) should always be
applied.
· All cancer patients receiving active anti-cancer treatment should be
under the care of specialist oncology or haematology staff.
· Trust chemotherapy policies and procedures must explicitly encompass
oral as well as parenteral chemotherapy.
· All anticancer drugs, whether conventional or non-conventional cytotoxics,
should be regarded as potentially hazardous, regardless of the intended
route of administration. Formal risk assessment should be applied to
determine for each drug the level of risk posed and hence the risk reduction
and management strategy needed.
· The prescribing and dispensing of oral chemotherapy should be carried
out and monitored to the same standards as those for parenteral chemotherapy.
· Responsibility for administration of oral drugs ultimately lies with
the patient (or a relative or carer) but it is the responsibility of
all members of the multidisciplinary oncology or haematology team to
ensure, as far as practically possible, they are adequately prepared
for this.
· Effective communication between primary and secondary care and with
patients is pivotal to safe and effective treatment.
· Other than in exceptional and clearly defined and mutually agreed circumstances,
prescribing and dispensing should remain the sole responsibility of the
hospital-based oncologist or haematologist and pharmacy, respectively.
Prescribing
· Prescribers should have expert guidance and support at the point of
prescribing.
· All anticancer drugs should be prescribed only in the context of written
protocols.
· The treatment plan should be documented in the notes and should include
criteria for modifying and stopping treatment.
· Electronic systems, or prescription proformas or templates, similar
to those for parenteral chemotherapy, should be used.
· Prescriptions must state clearly for each course of treatment, the
dose, frequency of administration, intended start date, duration of treatment
and, where relevant, the intended stop date.
· For drugs for which a variety of schedules are in common use it is
especially important that the intended schedule is unambiguously specified
on every prescription. (For example, some drugs may be given as two weeks
on treatment and one week off, three weeks on and one week off, two weeks
on and two weeks off or continuously.)
· All intended deviations from protocol, such as dose modifications,
should be clearly identified as such.
Dispensing and labelling
· Prescriptions must be screened by authorised pharmacists before dispensing.
· All pharmacy staff who are, or could be, involved with dispensing oral
anticancer drugs must have access to full copies of all the relevant
protocols.
· All dispensary staff must have ready access to specialist oncology
pharmacy advice.
· The information available to dispensary staff must address the management
of toxicity, the criteria for mid-course dose adjustments or stopping
treatment, and identify in what circumstances and with which drugs continuous
rather than
intermittent treatment may be used.
· This information should be available for all regimens, both in and
outwith the context of clinical trials.
· Dispensary staff should work to detailed operating procedures analogous
to those used for dispensing parenteral chemotherapy.
· The format and detail of dosing instruction should be standardised
and approved by an appropriate senior pharmacist. Label directions must
be clear and unambiguous and include where relevant, the intended period
of treatment, start and stop dates (for short term or intermittent treatment)
and an appropriate indication of the need for safe handling.
· Although it is essential that all patents receive a manufacturer’s
patient information leaflet with their oral chemotherapy drugs the use
of unbroken patient packs may also pose risks to patients if they are
then given more tablets than are needed for the intended course of treatment.
The decision on whether or not to issue whole packs should therefore
be based on a documented local risk assessment.
· Manufacturers’ patient information leaflets may be supplemented
with locally developed information.
· Consideration must be given to the management of patients with swallowing
difficulties. Avoid breaking or crushing tablets or opening capsules
whenever possible — queries should be directed to the local pharmacy
medicines information service — the advice of an oncology or technical
services pharmacist must be sought. Use of a suspension or solution is
preferred and a suitable preparation should be obtained from an NHS hospital
pharmacy or commercial compounding or manufacturing facility with appropriate
safe-handling facilities.
Patient education and information
· Before every treatment cycle, all patients should be seen by a specialist
pharmacist or nurse.
· The pharmacist or technician handing the drugs to patients (or relatives
or carers) must ensure that they fully understand:
· how and when to take their medicines (Some patients may find it particularly
hard to remember the idea of repeated short courses of treatment with “gaps” between
them.)
· what to do in the event of missing one (or more) dose(s)
· what to do in case of vomiting after taking a dose
· likely adverse effects and what to do about them
· the need for and how to obtain further supplies
· the role their GP is expected to play in their treatment
· principles of safe handling, storage and disposal
· that if used, medicine spoons or measures should be used once only
and then disposed of safely
· As much of this information as possible should first be given at the
pre-treatment visit and reinforced on subsequent visits
· This responsibility should be confined
to staff who have received training
specifically for the role. When drugs are handed to the patient by non-pharmacy
staff this should be the responsibility of a specialist nurse trained
to the same standard.
Access to advice and support at home
· Patients should be provided with details of appropriate and readily
accessible 24-hour points of contact with medical, nursing and pharmacy
staff to which they can direct queries.
General risk management
· Prescribing and dispensing arrangements and procedures should take
into account the:
· risk of wastage due to the possible need for interruption of treatment,
dose modifications, inappropriate storage, loss of medicines by a patient
· risk to others, especially young children, if the medicine is not safely
stored in the home
· Trusts should also consider the implications of the changes in activity
type on their contract income. This will further depend on whether treatment
consists of single agent oral therapy or an oral and intravenous combination
regimen.
Audit
· All aspects of practice should be subject to regular audit.
ACKNOWLEDGEMENT The introduction to this position statement was adapted
from O’Neill VJ, Twelve CJ. Oral cancer treatment: developments
in chemotherapy and beyond. British Journal of Cancer 2002;87:933–7.
References
1. Cassidy J, Twelves C, Cameron D, Steward W, O’Byrne K, Joddrell
D et al. Bioequivalence of two tablet formulations of capecitabine and
exploration of age, gender,body surface area and creatinine clearance
as factors influencing systemic exposure in cancer patients. Cancer Chemotherapy
and Pharmacology 1999;44:453–60.
2. Lee CR, Nicholson PW, Souhami RL, Deshmukh AA. Patient compliance
with oral chemotherapy as assessed by a novel electronic technique. Journal
of Clinical Oncology 1992;10:1007–13.
3. Lebovits AH, Strainn JJ, Schleifer SJ. Patient non-compliance with
self-administered chemotherapy. Cancer 1990;65:17–22. |
The
Pharmaceutical Journal
On this and the following page is a position statement
from the British Oncology Pharmacy Association on safe practice and
the pharmaceutical care of patients receiving oral anticancer chemotherapy