Pain is probably one of the most frightening cancer symptoms for patients and their families. Patients with moderate to severe cancer-related pain frequently require the use of opioid treatment. Fentanyl, the main component of TDF, is an effective alternative to oral morphine in patient with stable opioid requirements[8
. In particular, in patients who are unable to take oral medication, it provides constant delivery of fentanyl by less invasive means.
Fentanyl can be delivered in a transdermal controlled release formulation, providing continuous, controlled systemic delivery of fentanyl for up to 72 hours
. Fentanyl in the form of transdermal therapeutic system does not undergo the first-pass effect in liver or is not affected by gastrointestinal absorption. The absolute extent of bioavailability is close to 100% considering the dose derived from the claimed absorption. In adults upon initial application, serum fentanyl concentrations increase gradually, generally levelling off between 12 and 24 hours and remaining relatively constant for the rest of the application. In adults, the serum fentanyl concentrations attained are proportional to the size of the patch, and with repeated 72-hour applications, steady state serum concentration is maintained during subsequent applications of a patch of the same size
Two different types of transdermal fentanyl delivery systems are currently available on market: reservoir and the matrix patches. In a reservoir formulation fentanyl is sandwiched between an occlusive backing layer and an adhesive controlled-released membrane and delivery is determined by the special rate-controlling membrane. Recently, novel matrix delivery systems have been introduced. In a matrix formulation, fentanyl is completely dissolved in an adhesive polymer matrix, from which the drug is continuously released into the skin. The dose of drug delivered depends on the amount of drug held in the matrix and the area of the patch applied to the skin. The active ingredient is distributed evenly throughout the patch, so one-half of a patch will have half the original surface area and deliver half the original dose per hour. Good adhesion of the transdermal patch to the skin is essential for maximum efficacy; therefore patients must be instructed on the proper technique for patch application. The novel matrix and reservoir transdermal delivery systems of fentanyl were safe and equally well tolerated. The pharmacokinetic profiles of reservoir and matrix patches are similar, and two delivery systems were considered bioequivalent since they resulted in similar rates and extents of exposure of fentanyl[26
. However, the matrix formulation has a number of advantages over the reservoir formulation. Compared to the old system, there is a lower risk of accidental overdose with membrane damage for the matrix type. Furthermore, the new system is expected to be more convenient and more comfortable to wear than the old system due to its smaller size and better adhesive properties. Therefore, the reservoir patch is currently being phased out in nearly all market and replaced with the new design.
The new transdermal fentanyl in matrix formulation has been shown to be comparable in efficacy to standard morphine or fentanyl in reservoir formulation in patients with moderate to severe cancer-related pain[29
. This observation is in accordance with the results of previous studies with TDF treatment. Total pain remission rate was 91.29% and there was no significant difference between opioid-naive patients and previously opioid treated patients. For the reason that most patients in this study suffered from chronic visceral pain and/or bone pain but not neuropathic origin[2
, analgesic effect was remarkable.
Many studies demonstrated that one of the advantages of TDF was significantly lower incidence of AEs especially constipation compared to other oral opioids used for pain control, while some others reported the equal incidence
. TDF was found to be safe and well tolerated in this population. The incidence of AEs was 33.75% in our research and the majority of AEs were judged to be mild or moderate in intensity and easy to be managed, similar to most literature reported. No life-threatening or disabling side effects were observed in our study. The most frequent AEs during TDF treatment were constipation, nausea, vomiting, stomach discomfort, dizziness, drowsiness and dysuria, most of which involved the gastrointestinal system and central nervous system.
Respiratory depression is the most serious and potentially life-threatening adverse effect. In the post- marketing experience, deaths from hypoventilation due to inappropriate use of TDF have been reported. Clinically relevant respiratory depression was not observed in patient with chronic pain on opioid analgesics in three randomized trials, but serious or life-threatening hypoventilation has been documented in opioid-naive patient and in the postoperative setting[33
. Consequently, patient with hypoventilation should be carefully observed and their respiratory rate must be monitored until respiratory status has stabilized. Two (0.42%) patients developed mild hypoventilation in this study, which was judged to be “probablely” related to study medication, and both of them experienced self-recovery.
QOL scores clearly improved with the use of TDF. After 2 weeks of treatment, total score of QOL in 91.25% patients increased and each item scores improved to different extents. These findings are especially important for these enrolled patients because most of them were in palliative care and nearing end of their lives.
Furthermore, 85.59% (122) of the initial patches administered in the study were still almost completely to completely adhered to the skin at 72 hours, which ensured the efficacy of study medication. In addition, 91.03% investigators and 87.09% patients were satisfied to very satisfied with the new system. The transdermal therapeutic system is needle-free, easy and convenient to use. Therefore, significantly more patients expressed a preference for transdermal fentanyl than for other opioids in future.
The novel TDF, as a useful alternative to other opioid agents, offers a significant improvement of pain treatment in patients with moderate to severe cancer pain. In addition, transdermal fentanyl is safe and well tolerated and the vast majority of patients in this study were satisfied with it.