Capecitabine (Xeloda, Roche) is an oral chemotherapy drug developed for use in place of some intravenous chemotherapy regimens in specific cancers and it is important, as with intravenous (IV) chemotherapy regimens, to carry out a toxicity assessment and to provide patients with support. This paper explores a service development in St Luke’s Cancer Centre, Surrey and in the Surrey, West Sussex and Hampshire Cancer Network that involved introduction of this new oral chemotherapy agent.
Paula Deery, RGN, OncCert
Chemotherapy Practice Development Sister, Royal Surrey County Hospital
Innovations in health technology can have rapid and profound changes on service delivery, as can the developments in outpatient services, new surgical procedures, drugs and devices, enabling many interventions to take place outside the inpatient setting (Cameron, 2000). The speed with which these changes occur is increasing and there is now greater emphasis on ambulatory health-care services and primary care.
This paper examines the introduction of an innovation in cancer chemotherapy involving administration of a new oral chemotherapy drug, capecitabine and explores its use as a therapy in a cancer centre.
The term chemotherapy refers to the use of cytotoxic (toxic to cells) drugs or chemicals that prevent cancer cells from multiplying, invading adjacent tissues or developing metastases. It is one of several treatment modalities used in treating cancers (the others include surgery, radiotherapy and hormone therapy).
In considering the use of chemotherapy, it is necessary to take into account factors such as histology, stage of disease at diagnosis, presence/ absence of metastases and the ability of the patient to withstand treatment and side-effects. The aims of chemotherapy could be to achieve a cure, to control disease or to relieve symptoms of the cancer, such as pain or breathlessness.
A new cytotoxic agent
Since its development in the 1950s, 5-fluorouracil (5-FU) has remained one of the most extensively used chemotherapy drugs for treating cancer. It is part of many standard cancer regimens, used either as a single agent or in combination with other cytotoxic drugs for solid tumours, including colorectal and breast cancers. Owing to the unpredictable nature of how oral 5-FU is absorbed, it has been administered intravenously, either as a bolus injection or, more commonly, as a continuous infusion.
The continuous infusional route of administering 5-FU requires the insertion of a central venous access device (CVAD), which is performed on a day-case/outpatient basis. The treatment is delivered over a week via a small pump which has to be carried by the patient at all times throughout treatment. Patients and carers require education on caring for the CVAD and pump, and need regular support from the primary care and cancer teams (Dougherty and Viner, 1998).
This route is associated with greater inconvenience for patients and service costs (Meta Analysis Group in Cancer, 1998). Complications, such as thrombosis and infection, may lead to hospitalisation and can interrupt therapy (Koeppen and Caspers, 1994). Thus, administering chemotherapy via a route that would not only avoid these problems but would be just as effective would improve a patient’s quality of life.
Capecitabine was developed as an oral agent capable of mimicking a continuous 5-FU infusion. The drug is rapidly and almost completely absorbed in the upper gastrointestinal tract as an intact molecule, reducing risk of local toxicity. It then converts to 5-FU via a three-way enzymatic cascade, with the final step in the process being mediated by the enzyme, thymidine phosphorylase (TP). The enzyme is highly active in most solid tumours. Its activity in cancer tissue is three to 10 times higher than in corresponding normal tissue (Miwa et al, 1998). Capecitabine, therefore, has potential for use for a wide range of cancers, including colorectal, breast, gastric, cervical, uterine, ovarian and renal tumours, as well as liver metastases from colorectal tumours.
The use of oral chemotherapy agents is not a new concept: drugs such as chlorambucil, procarbazine, melphalan, lomustine and cyclophosphamide are administered orally for treating some cancers. However, because of pharmacological problems with absorption and how the body metabolises drugs, oral cytotoxic agents have not been used extensively in cancer treatment (Tortorice, 2000).
Oral chemotherapy has obvious benefits for patients. However, compliance with taking medication must be considered should the number of tablets be excessive. Patients’ perceptions or attitudes to oral chemotherapy may affect the overall success of treatment as they may not think they are as ill as those receiving IV therapy because they self-administer the drugs. They should be informed that oral chemotherapy is as effective as IV treatment, provided it is taken correctly and interrupted appropriately if side-effects develop.
To replicate the continuous nature of 5-FU delivery patients must take medication consistently. The standard treatment with capecitabine as a single-agent drug for patients with metastatic colorectal and breast cancer is 1250mg/m2. Tablets are taken twice daily, within 30 minutes of eating breakfast and dinner, for 14 days, with one week off, which improves compliance. This cycle continues until the treatment stops being effective or the patient is unable to tolerate it. Patients on oral chemotherapy need to be aware of, and monitor, their side-effects as toxicity will affect the dosing regimen and delivery.
Although it may be more convenient for patients to be treated at home, side-effects and toxicities can have a major impact on quality of life and will require close monitoring. Health education and broader support strategies help prevent problems and ensure safe delivery of chemotherapy agents.
Developing cancer services
Changes in service delivery require careful management to implement research in practice (Tolson, 1999). It is crucial not only to ensure that information is transferred from researchers to those providing health-care services (Harvey et al, 2002), but also to change attitudes towards oral chemotherapy. Studies show that the barriers to change in health-care settings (Rutledge et al, 1998; Johnstone et al, 2000) are not only a lack of research awareness, but also a sense of scepticism of its benefits and an unwillingness to try new things (Nagy et al, 2001). More commonly, though, the barriers are organisational: for example, insufficient authority to change patient pathways, lack of physician co-operation, insufficient time to implement ideas or inadequate facilities (Nilsson et al, 2001; Parahoo, 2000)
Few resources are usually allocated to implementing innovation in practice (Haines and Jones, 1994). Strategies for implementation need to be made sustainable and dynamic to ensure they meet the changing needs of health care but this requires planning. Davies (1999) advises that, before embarking on changes, it is important to consider what is to be changed, how such change might be brought about effectively and efficiently, and how it can be monitored and evaluated.
What needs to change
The key priority was to develop and define the patient pathway for those receiving capecitabine, defining the care required, information resources, and the patient support necessary both outside and within the cancer centre.
Responsibility for the project fell to the practice development sister, whose role in the cancer centre includes educating and supporting staff on issues relating to chemotherapy. A mapping exercise was undertaken to assess how patients receiving oral chemotherapy were being managed. Traditionally, outpatients on oral chemotherapy were issued with a prescription that would be collected by the patient or carer from pharmacy before they returned home. There was no formal home follow-up but the patient could ring the unit for support or if they felt unwell.
The mapping exercise highlighted the fact that it was difficult to assess quality and consistency of information because consultations took place in different settings and because patient information and checking their understanding were not being done. The key factor was changing attitudes about the fact that patients on oral chemotherapy need as much support as those using the IV route.
The patient pathway
A working group, consisting of practitioners from a range of settings, was set up to develop a patient pathway. It was agreed that a more formal approach to managing patients on oral chemotherapy would be required. For the first three cycles they would attend the chemotherapy clinic where trained nurses would provide education and information, as well as assess a patient’s physical and psychological symptoms. The clinic would also be a central point of contact for patients and health professionals.
How to effect change
The aim of changing existing service patterns was to better inform and educate both patients and health professionals (in both the hospital and primary care teams) on the use of capecitabine to minimise potentially serious complications by early recognition and intervention. It is also important to identify patients at particular risk and to alert primary care teams. Attendance at the chemotherapy clinic seeks to minimise the risks to those on oral chemotherapy because having access to staff knowledgeable about management of the drug can avoid occurrence.
One of the essential elements to making change successful is in communicating change. Engaging in discussions with community staff, GPs, chemotherapy nurses and oncologists made it possible to prepare locally based guidance based on an analysis of what measures were needed to introduce this change. The importance of involving the primary care team in a service development that involved a new oral chemotherapy drug is one of the keys to successful management of patients having cancer therapy (Turner and Pateman, 2000).
Personal contact with colleagues is an important way of bringing about change (Stocking, 1992). Information relating to treatment management or support for patients on continuous infusional chemotherapy, for example, is normally conveyed via a telephone referral and supported with a letter containing similar information. For patients on oral chemotherapy, the process would be the same; however, developing printed educational materials required a different approach.
The successful management of patients needs to depend not only on the assessment made by district nurses but also on the quality of the information supplied to them by the centre. Primary care teams often criticise hospitals for sending copious documentation, which often arrives late, is too complex or not relevant to primary care team practice. Information needs to be stored with the patient’s record, so the documentation developed had to be concise and not bulky. A pro forma was created to provide details about each patient and included important issues relating to treatment that could be posted or faxed to the community staff. Often, when change is instigated for primary care teams, they are exhorted to change practice and, while they may be provided with the knowledge, they are often not offered practical help (Dietrich, 1994). So it was important to provide consistent information and to offer support to clinicians through the practice development sister, who was the key link in the process.
Education for members of the multiprofessional team was instigated through staff seminars for all those involved in prescribing, dispensing, providing information to patients and carers and the primary care team. On the hospital side, it included doctors at all levels, nurses, nurse managers, staff from outpatient and chemotherapy clinics, research nurses and those in the wards. A representative from the drug company facilitated the sessions. Pharmacy staff, especially those in the dispensary, not only had a vital role in dispensing the drugs but also in planning the project pathway as it was to be their role to instruct patients to return to the chemotherapy clinic.
A chemotherapy drug chart that incorporated the details required for the prescription, including the patient’s body surface area and calculated creatinine clearance, was devised. This was done with the intention of aiding physicians in checking relevant clinical assessment and to alert dispensary staff to the new chemotherapy drug being issued, as well as to remind them to advise the patient to return to the chemotherapy clinic for information or follow-up.
To target the primary care team, a list of names of key nurses and GP practices within the network was obtained. Telephone contact was made with them by the drug company representative to organise how the educational programme that had taken place in the cancer centre could be rolled out to community staff. During the sessions, attended mainly by district nurses, discussion centred on clinical issues relating to the importance of early recognition of toxicities, communication between hospital and primary care teams, and the documentation specifically designed for the project, such as the toxicity guidelines document.
Clinical guidelines are also an important way of changing practice (Davies, 1999). The toxicity guidelines document was developed to provide GPs and district nurses with important information about the drug and was to be patient-specific to enable it to be filed in records.
The document included information on when treatment started, drug side-effects and their management, possible drug interactions and 24-hour contact details for hospital staff. A section was included for additional comments to enable hospital nurses to provide community staff with information on possible compliance problems in vulnerable groups such as elderly people or those with hearing or visual impairments, or if the patient was entered in a clinical trial that included the drug. These were posted to GPs and faxed to district nurses after telephone referral. The patient was given a copy to keep at home if they needed to call medical staff who may be unfamiliar with the drug.
Crucial to making changes in practice is the involvement of patients: they are best placed to question existing practices and to demand information about new procedures (Davies, 1999). The need for patients to be self-aware, to check symptoms and report back if problems arise, highlighted the need to develop and support the patient.
At their first visit to the chemotherapy clinic, patients are given verbal information and education about the oral chemotherapy drug. A patient guidance information sheet was developed to act as an aide memoire. It explains why the drug is being used, its constituents, contraindications for use, possible allergies, interactions, side-effects and advises of correct storage. It also provides 24-hour contact details of the cancer centre. It is used to back up the verbal information given by clinic nurses and is kept by the patient at home. The information it contains is also useful to members of the primary care team who may be unfamiliar with the drug and its side-effects.
The use of diaries for monitoring and logging of symptoms is widely used in other areas of practice for clinical assessment. A diary is issued to the patient on oral chemotherapy; this contains the treatment details, including the number of tablets to be taken each day, dosages and possible side-effects. Patients are encouraged to use the diary to record side-effects they experience and to monitor progress. This helps medical and nursing staff to build up a profile of how the oral chemotherapy drug is affecting patients and to detect potential problems earlier. After treatment is completed the diaries are kept in patients’ records and, with their permission, can be used as an audit tool.
All the documentation, created for this project by the practice development sister, was included in special coloured packs put together in advance to minimise the amount of time spent by nurses on paperwork. They included the standard documentation, such as the chemotherapy referral form, consent form, drug chart and nursing documentation. Documentation created specifically for the project included were:
- Toxicity guidelines document: a double-sided A4 sheet containing information about the drug, its side-effects and instructions on how to monitor them, details of drug interactions, a space for comments in case of vulnerable patients and the 24-hour contact details of the cancer centre. The document was designed to be patient-specific by means of attaching an identity sticker before it was sent to the primary care teams.
- A sheet containing key points and instructions for nurses to give to new patients. It would act as an aide memoire for staff unfamiliar with the drug and ensure consistency of information provided
- Information for GPs: a brief covering letter was printed to inform them about the toxicity guidelines document; an envelope required to post the documents in was included in the pack
- Documents for district nurses: a fax cover sheet was printed to minimise the time spent when sending them the toxicity guidelines
- Guidelines for patients on oral chemotherapy.
The packs were prepared for specific disease sites, for example, colorectal and breast cancers, and were identified by means of a coloured sticker attached to the front of the packs.
Davies (1999) suggests it is important to evaluate and monitor the effectiveness of the implementation when instigating change. Now that the oral chemotherapy service has been in operation for one year the next step in our practice development is to evaluate the patient pathway.
Developing services to meet innovations in treatment delivery is not a simple task. While it is important to inform all relevant practitioners, it is also essential to support clinicians through the process of developing local clinical guidance, patient information and education. As an oral chemotherapy agent capecitabine has the potential to improve a patient’s quality of life and offers greater independence to patients having treatment at home. However, it is also important to consider patients’ attitudes and awareness of treatment side-effects to help the primary care team to monitor and respond to symptoms effectively. The team has successfully met the challenge of monitoring patients on this new drug and their role will continue to remain important in assessing toxicities and patient compliance.
Further clinical trials of oral chemotherapy are under way, and we will be seeing it used more frequently to target different disease sites. It may be used in an adjuvant setting, as well as in combination with other treatments, such as radiotherapy.
Evaluation of the drug’s efficacy and side-effects has not yet been undertaken. However, informal observation would suggest that the need to manage side-effects could be reduced if patients were educated and informed at the outset of treatment in the chemotherapy clinic. It also seems evident that the new programme has improved the knowledge of health-care professionals about the drug and its profile.
Members of the working group
Dr G. Middleton, Consultant Medical Oncologist
Dr C. Topham, Consultant Clinical Oncologist
Carol Redfern, Lead Nurse
Margaret Powell, Deputy Lead Nurse
Rebecca Slee-Smith, Oncology Nurse Manager
Isabel Patterson, Oncology Out-patient Manager
Judith Moore, Clinical trials Co-ordinator
Claire Palles-Clarke, Breast Research Sister
Carolyn Tucker, Senior Oncology Pharmacist
Rebecca Lagden, Aseptic Services Manager
Julie-Anne Cox, Roche Hospital Sales Specialist
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