Is Tapentadol An Effective Treatment For Cancer Pain

The life expectancy of cancer patients has significantly improved due to advancements in early diagnosis and treatment of the disease. Therefore, it is more likely that patients will perceive their particular cancer pain as chronic pain. As a result, long-term management of cancer-related pain and the pain associated with oncological therapy is crucial for all patients and a problem for all health providers.

Tapentadol is a centrally-acting analgesic drug with synergistic mechanisms of action. It acts at the µ-opioid receptor and inhibits noradrenaline reuptake. Tapentadol is, therefore, regarded as the pioneer of the MOR-NRI drug class. 

Tapentadol has been evaluated on various cancer patient populations (opioid-naive and -pretreated), including those with pain of mixed causes, advanced cancer, and advanced-stage patients. Let us see this in detail.

In 2019, the United States reported 1,752,735 new cancer cases, and 599,589 people died of cancer. After heart disease, cancer is the second leading cause of death in the US.

"Cancer Statistics, 2022," published in the American Cancer Society Journal, states that an estimated 1.9 million new cancer cases will be diagnosed and 609,360 cancer deaths in the United States in 2022. This estimate excludes basal and squamous cell skin cancers, as cancer registries do not require reporting them. 

What Is Tapentadol?

Tapentadol is a centrally-acting analgesic that works by a dual mechanism. It acts by activating mu-opioid receptors and inhibiting norepinephrine reuptake. It helps to relieve moderate to severe pain in adults.

Tapentadol is distinct from classic opioids and thus may be suitable for chronic, neuropathic, and mixed pain. Therefore, it can be considered a general-purpose analgesic for moderate to severe cancer pain in opioid-naive and opioid-pretreated patients. 

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What is Cancer?

Cancer is a category of disorders marked by uncontrolled cell proliferation and invasion into other body regions. Cancers result from specific changes at the molecular level in response to various stimuli.
Numerous factors are known to increase the risk of cancer:

• Physical carcinogens, such as UV radiation
• Chemical carcinogens, such as components of tobacco smoke, alcohol, aflatoxin, arsenic, and asbestos;
• Biological carcinogens- certain viral or bacterial infections 

Types of Cancer Pain

People who have cancer may experience moderate to severe pain. As cancer progresses, pain can become worse. It can dull aching, stabbing, or burning. Most cancer pain is manageable, and controlling your pain is essential for treatment.

Acute pain: Acute pain is short-lived. The cause can be easily identified, such as an activity that causes it. The pain goes away when the wound heals.

Chronic pain: Chronic pain may be due to cancer pressing on the nerves or to chemicals produced by a tumor. Nerve changes resulting from cancer treatment can also cause pain. Chronic pain lasts long after the injury or treatment and can range from mild to severe.

Somatic pain: The patient feels pain in body parts, such as bones, muscles, joints, and ligaments. It may be aching, dull, or throbbing in nature.

Neuropathic pain: Caused by pressure on nerves or the spinal cord or by nerve damage. People often experience it as a burning or tingling sensation.

Visceral pain- Viscera are the soft, internal organs in areas of the body, such as the chest, abdomen, and pelvis. The patient feels pain in an organ in one of these areas. The origin of the pain is difficult to pinpoint because it is diffuse and widespread. 

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What Causes Cancer Pain?

• Most cancer pain is due to the tumor pressing on bones, nerves, or other organs in the body.
• Sometimes the pain may be due to cancer treatment. For example, some chemotherapy drugs can cause numbness in your hands and feet. Or they may cause a burning sensation when the drug gets injected.
• Radiation therapy often results in skin redness and irritation.

Tapentadol For Cancer Pain

Tapentadol provides excellent analgesia with good tolerability. It combines opioid receptor agonist activity with norepinephrine reuptake (NRI) suppression.

Tapentadol may benefit cancer patients who experience frequent nausea, vomiting, constipation, or other events that reduce their quality of life. Its fewer gastrointestinal side effects and favorable Safety profile make Tapentadol an appealing option for some cancer patients.

How Does Tapentadol Work?

Tapentadol reduces pain through two action modes: MOR(mu-opioid receptor) agonism and NRI (noradrenaline reuptake inhibition). Compared to delta- and kappa-opioid receptors, it has a more than or equal to a ten-fold affinity for MOR. Tapentadol has a 44-fold reduced affinity for MOR than Morphine.

NRI raises noradrenaline (NA) levels, which activates inhibitory alpha-2 receptors to provide analgesia. Its opioid-sparing actions are a result of this dual mode of action. Although Tapentadol has a negligible effect on serotonin reuptake, it does have an analgesic effect.

Studies Related To Tapentadol Use in Cancer Pain

In a four-week prospective study by Mercadante et al., 50 opioid-naive cancer patients with moderate-to-severe pain participated; each patient received 50 mg of Tapentadol PR twice daily, and doses were adjusted following the patients' clinical responses. Thirty-nine patients completed the study in total. 

As of the first week, pain intensity was significantly reduced compared to the baseline, and the study's duration improved the quality of life. Individuals who previously used NSAIDs or paracetamol tolerated Tapentadol well with little to no side effects. There was no worsening clinical status—Tapentadol in cancer pain management: a prospective open-label study. 

Brunetti et al. investigated the Safety and effectiveness of Tapentadol PR in a retrospective trial. The study included 36 challenging patients with hematological malignancies and uncontrolled pain. Overall, there was a reduction in pain intensity without any pertinent adverse events—Tapentadol PR for pain syndromes in actual-life patients with hematological malignancy. 

Dosage of Tapentadol for Cancer Pain

Design the dosing regimen based on the severity of pain and previous treatment experience. Patients should begin treatment with 50 mg of Tapentadol administered every 4 to 6 hours. If the first dose did not provide adequate pain relief, initiate the second one hour later.

Acute Moderate- to-Severe Pain

• Immediate-release tablet or oral solution: 50-100 mg PO every 4-6 hrs; not to exceed 700 mg on day 1 and 600 mg/day following days.

Chronic (extended-release tablet)

• 50-250 mg
• Opioid-naive patients: Start with 50 mg BD every 12hr as needed; not to exceed 500 mg/day.
• Opioid-experienced patients: The initial dose depends on the type of the previous analgesic used.

Chronic Severe Pain

• 50-250 mg as needed every 12 hours; not to exceed 500 mg/day.
• Opioid-naive patients: 50 mg PO every 12 hours; titrated to optimal dosage as required; not to exceed 500 mg/day.

Possible Side Effects of Tapentadol

Side effects are undesired effects that occur after taking the drug. These can be expected or severe side effects. Talk to your doctor if any of the symptoms appear. 

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Other Alternatives for Cancer Pain

Treatment options for cancer pain include non-opioid analgesics, opioid analgesics, radiation therapy, and surgery. Adjuvant medications are also essential for pain control.

• Mild cancer pain can be treated with non-opioid analgesics such as paracetamol or NSAIDs (e.g., aspirin, ibuprofen, diclofenac). These can be given alone or in combination with opioids.
• Mild to moderate cancer pain can be treated with weak opioids such as codeine or tramadol. Physicians usually administer them with non-opioids.
• Treatment for moderate to severe cancer pain includes opioids such as morphine, oxycodone, fentanyl, and methadone.
• Morphine and fentanyl are common treatments for episodes of severe breakthrough cancer.
• Treatment options for cancer-related bone pain include radiation therapy, bisphosphonates, denosumab, and analgesics. Percutaneous vertebroplasty relieves spinal pain by stabilizing the bones.
• Pain due to spinal cord compression requires treatment with radiation therapy with or without steroids. Surgery also
• helps to remove the tumor or stabilize the vertebrae.
• Treatment of neuropathic pain includes opioid combinations, anticonvulsants, antidepressants, and lidocaine patches.

Precautions Before Taking Tapentadol

• Let your doctor know about any allergies or conditions you may have before taking a drug and any other prescriptions you may be taking.
• Inform your doctor if you are pregnant or breastfeeding. Tapentadol withdrawal symptoms have been observed in children born to moms who used the drug during pregnancy.
• If Tapentadol enters breast milk is unknown. It may affect your infant if you are breastfeeding while taking this medicine.
• Tapentadol may cause severe reactions like Serotonin syndrome if taken with other drugs that affect serotonin, such as tricyclic antidepressants and serotonin reuptake inhibitors.
• If you have a history of epilepsy or medical conditions that increase the risk of seizures since there have been seizure reports with Tapentadol.
• This drug may make you feel sleepy or less alert. Until you know how the medication affects you, avoid driving or doing other tasks requiring attentiveness.
• Alcohol and anti-anxiety drugs may increase the drowsiness brought on by this medication.

Bottom Line From Practical Anxiety Solutions

Pain can be a long-term side effect of cancer treatment. It is important to tell your doctor or nurse about persistent or new pain so they can help you manage it. Many effective treatments can relieve pain at all stages and for all types of cancer.

Interestingly, a Cochrane review from 2015 found that Tapentadol proved to be at least as effective in relieving cancer patients' pain as morphine or oxycodone. 

Tapentadol's lower incidence of gastrointestinal side effects and generally positive Safety profile make it a suitable alternative for cancer pain patients. Another significant benefit of Tapentadol in cancer patients receiving intensive pharmacological therapy is its minimal likelihood of experiencing drug-drug interactions. Tapentadol can be regarded as an acceptable option for supportive treatment in those cancer patients who are most at risk and likely to develop gastrointestinal side effects.