Long-Term Safety of Oral Transmucosal Fentanyl Citrate for Breakthrough Cancer Pain

Authors: Payne R, Coluzzi P, Hart L, et al.
Source:Journal of Pain and Symptom Management, Vol 22 (1), 575-583, 2001

Background

• Treatment of pain is very often an important part of a cancer treatment regimen
• Standard pain treatment regimens include long-acting, baseline (usually narcotic) pain medication with supplemental pain medication as needed for "breakthrough pain", which are flares of pain not controlled by the baseline medication
• Breakthrough pain is usually treated with a short-acting oral opioid
• Because of the slower onset of oral medication, there can be delays in the relief of breakthrough pain
• Oral transmucosal fentanyl citrate (OTFC) has a rapid delivery and absorption for quicker relief
• Although OTFC's safety has been evaluated in the short-term, this study evaluates its use over a long period
• This is especially important as patients with cancer pain are likely to require medication for extended periods

Materials and Methods

• Study of 155 patients who had previously been on a short term study of OTFC
• Patients were required to have baseline narcotic requirement, at least one episode of breakthrough pain per day, and relief of this breakthrough pain by narcotics
• Baseline narcotics could be increased at the physician's discretion
• Patients used the dose of OFTC for breakthrough pain that had been successful in the short term study
• Patients could use up to four units per episode of breakthrough pain
• A successful treatment of breakthrough pain was defined as adequate pain relief with one unit of OFTC
• Data regarding efficacy and safety were obtained via a questionnaire filled out by the patients

Results

• Of 167 patients who had participated in a short term study of OFTC use, 155 (93%) participated in this long term study
• About half of the patients were male, average age was 54 years, with 23% of patients taking OFTC for neuropathic type breakthrough pain
• A mean number of 277 units were used per patient over a mean period of 91 days
• Adverse effects of OFTC use were somnolence, constipation, nausea, dizziness, and vomiting. None occurred in more than 9% of patients.
• Only 6 (4%) of patients stopped OFTC use due to toxicity
• 61% of patients never had to increase their dosage of OFTC for breakthrough pain, while 36% required an increase in dose of OFTC
• 92% of breakthrough pain episodes were successfully treated (with only one unit of OFTC)
• Global satisfaction ratings on the questionnaire were consistently on the very good to excellent scale

Author's Conclusions

• Patients who were successfully titrated to an effective dose of OFTC can benefit from long term use
• OFTC use is safe and effective in the long term
• OFTCs can be useful therapy in the long term management of breakthrough pain in cancer patients

Scientific Implications

Pain is likely the most debilitating symptom from cancer. The majority of patients diagnosed with cancer will require analgesic therapy at some point during the course of their disease. Though this is recognized, pain continues to often be undertreated. The obvious, though often overlooked, problem with breakthrough pain, is that patients must experience pain before they can be treated for it. Hence, the quicker the relief, the better. Oral transmucosal fentanyl citrate has a very quick onset and has demonstrated safety and efficacy in shorter trials. This trial does demonstrate its safety and efficacy in the long term. Taking away from the strength of this study is that it was conducted in patients who were already pre-selected (by their participation in a short term study) to respond to OFTC and without any direct comparison to other short acting narcotics or placebo. Also, the majority of the data collected was from a questionnaire self scored by the patients. This always has flaws. However, because of its effectiveness, rapid onset, and reports of toxicity that are consistent with other short acting narcotics, OFTC units can be very useful in the treatment of breakthrough pain in the chronic setting. One concern with OFTCs, as pointed out by the authors, is the fact that the units resemble a lozenge attached to a handle and could potentially be abused by children. Care must be taken to insure against accidental use.