radiotherapy or capecitabine (at 825mg/m2) twice daily 5 days per week with ... Treating patients with capecitabine saves a median of 280 minutes in DTU per.
Metro North Hospital and Health Service Royal Brisbane and Women’s Hospital
The benefits and cost savings of capecitabine substituted for infusional fluorouracil in the neo-adjuvant treatment of rectal cancer Miranda King B. Pharm | Jessica Toleman B. Pharm | Courtney King B. Pharm | Dr Matthew Burge MB, ChB, FRACP | Dr David Wyld MBBS (Hons) FRACP Cancer Care Services, Royal Brisbane and Women’s Hospital, Metro North Hospital and Health Service Table 2. Unique complications of 5-FU infusion
Background
Complication
Historically fluorouracil (5-FU) based chemotherapy in combination with concurrent radiotherapy was regarded as the standard of care in the neo-adjuvant setting of locally advanced rectal cancer1. Recent studies have shown that capecitabine with concurrent long course radiotherapy provides equivalent outcomes to 5-FU based treatment1,2.
No. of patients
Failed PICC insertion
1
PICC requiring re-insertion
3
Severe PICC dressing reaction
2
PICC dressing dislodgment
2
Capecitabine has been observed to be as well tolerated as 5-fU with the exception of slightly higher incidence of hand and foot syndrome and gastrointestinal toxicity with radiotherapy1,3.
PICC insertion length adjustment
2
Blocked PICC line
3
Incomplete infusion after 7 days
4
Prior to its current unrestricted PBS listing, a major barrier to accessing capecitabine was cost as rectal cancer was not a listed PBS reimbursed indication4.
PICC exit site infection requiring oral Antibiotics
2
Clot (requiring ClexaneTM)
1
Systemic infection requiring IV antibiotics
1
PICC line damaged (break in line)
1
Admission to Hospital due to Coronary Artery Vasospasm
2
Systemic infection requiring antibiotics
1
Patients unable to complete treatment
8
5-FU based therapy requires a peripherally inserted intravenous catheter (PICC) insertion3. There are several complications associated with PICC lines such as infection, thrombosis and blockage. These complications are eliminated with the use of capecitabine2,3.
Table 3. Complications of Capecitabine
Aim
Complication
To quantify and compare the total healthcare costs of neo-adjuvant treatment of rectal cancer using oral capecitabine and radiotherapy to the current standard of care, 5-FU 7day infusion with radiotherapy in a metropolitan hospital.
Method Eligible patients were identified using retrospective reports from the CHARM prescribing software as well as concurrently via the iPharmacy dispensing system. Patients were treated with either a 5-FU continuous infusion (at 225mg/m2/day) with concurrent radiotherapy or capecitabine (at 825mg/m2) twice daily 5 days per week with radiotherapy for 5-6 weeks. Individual patient data was then obtained using a combination of electronic health records and patient chart audit. The cost of neo-adjuvant treatment with both capecitabine and 5-FU was recorded using our chosen manufacturers drug price list as well as prices listed in our dispensing program. The cost of PICC line insertion for 5-FU treated patients included cost of the PICC line as well as well as the staff cost per hour of 2 registered nurses and a radiographer. In addition to this, the cost of dressings for the PICC line per cycle were recorded as an average per patient. Medications used to treat complications associated with the PICC line were recorded, these included Warfarin, Enoxaparin, Urokinase and oral or intravenous antibiotics. All medication costs were obtained from the current dispensing system. The time cost of both treatments was also recorded using the check in and check out times logged in the hospital’s booking system. Time spent waiting for clinic appointment, time in appointment as well as time spent in the day therapy unit was recorded.
Results A total of 63 patients were included in the analysis, 33 treated with infusional 5-FU and 30 treated with capecitabine.
No. of patients
Coronary Artery Vasospasm requiring admission
1
Grade I Diarrhoea
1
Grade II Diarrhoea
2
Dose reduction required
1
Hand and Foot syndrome (Grade I)
1
Rash (Grade I)
1
Nausea (Grade I)
2
Patients unable to complete treatment
1
Discussion The results show a clear patient benefit for using capecitabine in this patient group due to lower complication rates, equivalent costs and less time spent at the in the cancer care centre. Capecitabine was also very well tolerated among patients with only 1 patient unable to complete the treatment course (see Table 3). Aside from these benefits, there were several intangible costs to the patients Quality Of Life (QOL) that should be considered. The social implications for 5-FU treated patients were unable to be measured. These patients spent double the amount of time at the hospital, had a visible infusional device attached to their upper torso and also had to deal with the the burden of taking additional medications for subsequent complications. An issue unique to treatment with capecitabine is adherence. During review it was noted that some patients were not compliant with prescribed doses or it was not clear whether they received enough supply to finish the treatment course. This highlights the need in some cases for staged supply (week by week dispensing) and documentation by prescribers of the amount of tablets supplied.
Conclusions
Despite the disparity of drug cost, the overall cost of treatment was almost equivalent when the cost of managing the PICC line was taken into consideration (see Table 1).
• The drug costs of 5-FU and capecitabine are approximately the same when PICC lines costs and complications are factored in
Table 1. Medicines, patients and costs
• Capecitabine patients time spent in the outpatient department per visit approximately half that of those treatment with 5-FU
is
Medicine
5-FU
Capecitabine
No. of patients
N=33
N=30
• Treating patients with capecitabine saves a median of 280 minutes in DTU per patient
Median Cost of drug
$999
$969
• PICC complications of various types are common
Median total time spent each week at the hospital was also calculated for each patient group. 5-FU treated patients required both a consultation and a visit to the day therapy unit for PICC line flushes, disconnection/reconnection of infusor device as well as dressing change. Their median total time per cycle was 123 minutes compared to 60 minutes for capecitabine patients who required only a consultation with the doctor.
• The role of the pharmacist in educating patients as well as dispensing exact quantities is valuable for patient compliance and ensuring they receive enough to complete treatment course
References 1.
Rates of side-effects were similar as expected however there were several unique complications in the 5-FU treated group related to the PICC line (see Table 2).
2. 3. 4.
Ralf-Dieter H, Wenz F, Post S et al. “Chemoradiotherapy with Capecitabine versus Fluorouracil for locally advanced rectal cancer: A randomized, multicenter, non-inferiority, phase 3 trial” The Lancet (oncology) Volume 13 June 2012 page 579-588. www.thelancet.com/oncology Chu E, Devita VT. Physicians’ Cancer Chemotherapy Drug Manual 2010. Chapter 2: Chemotherapeutic and Biologic Drugs. Jones and Bartlett Publishers Sudbury, Massachusetts. 2010 eviQ Cancer Treatment Online. Rectal Locally Advanced Fluorouracil (protracted Infusion) Chemoradiation. Cancer Institute NSW, NSW Government https://www.eviq.org.au/Protocol/tabid/66/categoryid/328/id/73/Rectal+Locally+Advanced+Fluorouracil+(Protracted+Infusion)+Chemoradiation.aspx Department of Health. The Pharmaceutical Benefits Scheme. Capecitabine 500mg tablet. Australian Government. http://www.pbs.gov.au/medicine/item/8362D
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