Malignant tumor pain is divided into pain caused by tumor invasion, pain caused by anti-tumor treatment, tumor-related pain and pain unrelated to tumor or treatment. Bone is a common site of malignant tumor metastasis, which can be divided into 3 types according to lesion characteristics, namely osteolytic, osteogenic and mixed types. Osteolytic bone metastases account for 70% of the cases and are commonly found in lung cancer and breast cancer; osteogenic bone metastases are commonly found in prostate cancer and bladder cancer, accounting for about 10%.
The main clinical symptom of bone metastasis is pain, which is also a common cause of pain in malignant tumors. Analgesic drugs are the main method to relieve the pain of bone metastases from malignant tumors, including non-steroidal anti-inflammatory analgesics, opioid analgesics, bisphosphonates, and adjuvant drugs. Adjuvant drugs include tricyclic antidepressants, anticonvulsants, glucocorticoids, etc.
Non-steroidal anti-inflammatory analgesics and opioid analgesics
Pain treatment for bone metastases follows the three-step guideline for malignancy: preferred oral and non-invasive routes of administration, stepwise administration, timely administration, individualized administration and attention to detail.
Non-steroidal anti-inflammatory drugs are the basic drugs for pain management of bone metastases. When pain relief is not effective or when moderate or severe pain occurs, opioid analgesics can be combined.
Opioid extended-release agents are used “on time” to provide continuous relief of bone pain, while fast-acting or short-acting analgesics such as morphine immediate-release tablets are used to control sudden (explosive) pain. They can be used in combination with bisphosphonates.
Commonly used NSAIDs include acetaminophen, ibuprofen, diclofenac sodium, indomethacin, naproxen, celecoxib, and cronoxicam.
These drugs have adverse reactions such as gastrointestinal, cardiovascular, renal, hepatic, central nervous system, hematological system, etc. Among them, gastrointestinal adverse reactions are the most common, which can cause gastritis, esophagitis, gastric and duodenal ulcers, bleeding, perforation and obstruction, etc., manifested as nausea, vomiting, epigastric discomfort or pain, diarrhea, vomiting blood, black stool, etc.
Commonly used opioid analgesics include morphine extended-release tablets, fentanyl transdermal patches, oxycodone controlled-release tablets, morphine immediate-release tablets, codeine, methadone, etc. Pethidine should not be used in the treatment of pain in malignant tumors. Adverse effects of these drugs include constipation, nausea, vomiting, skin pruritus, neurological system such as drowsiness or excessive sedation, whistling inhibition, etc.
Bisphosphonates
Bisphosphonates are stable analogues of pyrophosphonate molecules, which can inhibit the lysis and destruction of bone trabeculae by osteoclasts, prevent osteolytic lesions caused by tumor metastases, reduce bone resorption, alleviate bone pain and hypercalcemia caused by bone metastases and other bone-related events, so they can be used for bone pain and hypercalcemia caused by bone metastases of malignant tumors, and can be combined with analgesic drugs.
These drugs mainly include alendronate, pamidronate, zoledronic acid, risedronate, ibandronate, etidronate disodium, and clodronate disodium.
Adverse reactions and medication precautions for these drugs.
Well tolerated, major adverse reactions include gastrointestinal symptoms (e.g. epigastric pain, acid reflux), flu-like symptoms (transient bone pain, fever, fatigue, chills, and arthralgia and myalgia), asymptomatic decreased plasma phosphate levels without treatment, hypocalcemia, renal impairment, osteonecrosis of the jaw (ONJ), and occasionally mild reactions at the injection site.
The risk of osteonecrosis of the jaw after a few long-term bisphosphonates is from high to low for zoledronic acid, pamidronate, alendronate, risedronate, and ibandronate; factors that increase the risk of osteonecrosis of the jaw include chemotherapy, use of glucocorticoids, and poor oral hygiene combined with periodontal disease and periodontal abscesses.
When used intravenously, attention should be paid to the acute phase reaction, with the highest to lowest incidence of zoledronic acid, pamidronate, and ibandronate.
Adjuvant drugs
Adjuvant medication can be selected according to the condition in case of neuropathic pain. In the presence of burning pain and cramping pain, tricyclic antidepressants such as amitriptyline, promethazine, nortriptyline, and desipramine can be combined; tertiary amines (amitriptyline, promethazine) are more effective than secondary amines (nortriptyline, desipramine), but secondary amines are better tolerated.
In the presence of electric shock-like pain or gunshot-like pain or severe pinprick-like pain, anticonvulsants such as gabapentin or carbamazepine can be combined.
Non-steroidal anti-inflammatory analgesics and opioid analgesics are symptomatic treatments for bone pain in malignant tumors; bisphosphonates significantly reduce the osteolytic activity within the foci of malignant bone metastases and reduce the resulting hypercalcemia and hypercalcemia and osteolysis; antidepressants and anticonvulsants are used as adjuvant analgesics for neuropathic pain.