Intravenous flurbiprofen axetil can increase analgesic effect in refractory cancer pain

Pain is a common problem in cancer patient. About one-third of patients being treated for cancer have pain. More than two-thirds of patients with advanced cancer have pain [1]. Controlling pain and managing symptoms are important goals of cancer treatment [2].

Flurbiprofen is a non-selective cyclooxygenase inhibitor used in clinic as nonsteroidal anti-inflammatory drug [3]. Flurbiprofen axetil, an injectable prodrug of flurbiprofen [4], has been reported to be associated with a reduction postoperative pain [5, 6], propofol injection pain [7, 8], and in initial treated pain induced from cancer [9]. The role of flurbiprofen axetil are not yet clear in the routinely administration of refractory cancer pain. In the present study, we reported the role of intravenous flurbiprofen axetil in this area.

A total of 2109 patients were screened. 37 patients were enrolled based on the criteria (22 men, 15 women; mean [SD] age, 57[13] years, mean [SD] height, 161[9] cm; mean [SD] body weight, 56[11] kg). Other clinic characteristics of those patients were showed in Table 1.

Thirty-three cases of refractory cancer pain were received 50 mg of intravenous flurbiprofen axetil injection every day. Other four cases had to increase the dosage of flurbiprofen axetil to 100 mg a day for the reason of insufficient effect by 50 mg a day. Thirty-four patients were regarded as partial relief or complete relief. The total effective rate was 92%. The results of usage and analgesic effect were showed in Table 2.

In this study, we testified that intravenous flurbiprofen axetil injection could increase the analgesic effects in refractory cancer pain. Lipid microspheres (LM) were target-drug delivery carriers which could congregate selectively in the site such as inflammation or injuring blood vessel and change the distribution of drugs in vivo [13, 14]. Flurbiprofen axetil injection, 0.2 μm in diameter, was composed of lipid microspheres and flurbiprofen axetil[15]. It was target-congregated easily to tumor, especially malignant tumor for there had abundant fresh capillary vessel and released inflammatory factor. The latter could enlarge the fissure of endothelium cells and let it be taken up by macrophages and neutrophils. So, the biosynthesis of prostaglandin was restrained, and the analgesic effects of flurbiprofen axetil would be appeared [16]. Flurbiprofen axetil injection always had better analgesic effects in bone metastasis of tumor while nociceptor pain was mainly expressed [9].

Anaesthetic anodynes were always used in moderate and severe pain patients. It acted in central nerve system, and the analgesic effects was not relative with the site or kind of pain. But, side effects always happened, such as constipation, breath inhibition, drug dependence, even exciting central nerve system when it was used for long time [2]. Flurbiprofen axetil and other NSAIDs drugs acted in the site of distal nerve. Its analgesic effects were always not bad than anaesthetic anodynes when the inflammatory medium was liberated in the site of muscle, tendon, ligament, and bone. It could be used as first line anodyne and combined with anaesthetic anodynes in corresponding cancer pain [4]. Our results showed that intravenous flurbiprofen axetil had better analgesic effect to cancer pain with bone or vertebra metastasis. It could reduce the dosage of the anaesthetic drugs, or increase the analgesic effects with little side effect, especially in patient who had constipation or had a tendency of ileus. Our results showed the analgesic effect was better than the Ou Yang's report [9], and similar to the report by Xu et al [17]. Perhaps for the reason of insufficient cases, we found that flurbiprofen axetil had slight analgesic effect to cancer pain in abdomen.

The half-life time of flurbiprofen axetil was 5.8 hours. Its onset of action was about 15 minutes after being used, and continued about 3 hours in post-operation. When it was used in cancer patients, it began to work quickly about in 30 minutes, and the duration of action was about 9 hours [18]. So it was especially suitable for breakthrough pain to the patient who were using anaesthetic anodyne. We found that most patients could obtain analgesic effects after being added flurbiprofen axetil 50 mg while their pain could not be controlled by anaesthetic drugs. But in some patients, the analgesic effect was only maintained 3–4 hours. So it need to be used continually or time after time, or other analgetic administrations should be used to the patients whose had severe cancer pain but could not deal with mainline.

Sometimes oral NSAIDs drugs are restrictedly applied mainly for the reason to stimulate patient's gastric mucosa. Intravenous flurbiprofen axetil injection could avoid this side effect. In all of 1089 cases, the side effect incidence rate was very low about 2.9% [18]. Most side effects were in gastrointestinal tract such as nausea, vomit, diarrhoea or in neuropsychosis such as fever, fear cold, sleepiness, etc. Few cases expressed as subcutaneous bleeding or pain in the injecting site. Perhaps our cases were insufficient, no side effect of flurbiprofen axetil was found in this study.

In general, cancer pain is considered as chronic. The pain intensity ranges from mild to severe and present for a long time. Harmless approach to therapy such as by oral or by cutaneous are suggested by WHO. But, for some reasons as constipation and psychosomatic symptoms, there has many patients whose can not take drugs by oral, or can not be used cutaneous anaesthetic drugs, intravenous flurbiprofen axetil could exactly remedy the anaesthetic drug's shortcoming, and let itself to be an important switch drug.