Palliative Care Therapies

Abstract

Palliative care considered as a support care for anyone living with a complex disease such as cancer, it has a great role in decreasing the severity of illness and slowness loss of functions by symptoms control and management in different stages of cancer. Palliative care is a specialized care area bounded to deliver health care facilities to patients who suffer from direct, indirect symptoms, unmet needs, for prevention and relief suffering from psychological issues mainly emotional issues (depression, anxiety, and delirium) and physiological issues like (nausea, vomiting, fatigue, xerostomia, headache, osteoradionecrosis, hemoptysis, dyspnea, taste loss, and pain). So its goal is to prolong their survival with the best possible quality of life for both the patients and their families.

1. Introduction

Cancer considers the first cause of death globally and it is accounting for about 10 million deaths in 2020 [1]. It has bad impact on physical and social life. Patients with cancer may experience one symptom or more at one time. Those with advanced disease that characterized by breathlessness and metastatic cancer may have on average about 14 symptoms [2], including symptoms of cancer itself and the side effect of cancer therapies [3].

Non-curative therapy creates a multidisciplinary effort for patients whose disease is unresponsive to indicated treatment curative intent, so its purpose is life-enhancing and prolonging. Those patients will go through progressive disease, that makes patients suffer from restlessness as a result of their illness, strategies of treatment, which negatively affect their treatment and the recovering handle, so, it is fundamental to control and reduce such suffering, which makes them need a shift in the objective of medical care. Despite the fact, that life-prolonging treatment can provide prolonged disease control with the present armamentarium of treatment modalities, side effects such as pain, anxiety, depression, fatigue, dyspnea, diarrhea, loss of appetite, nausea, and vomiting, often reduce the patient’s quality of life [4, 5, 6, 7, 8].

In order to prevent/palliate these negative impacts of the outcomes of the disease and to enhance quality of life of patients and their families, the urgency for palliative care as the main goal in providing therapy and care for patients who face problems of life-threatening diseases. Palliative care can relieve of the patient’s suffering by early identification, evaluation and treatment of physical, psychological, and social problems that include request for hastened death, assistance with making decision or care planning, patient demand for referral, spinal cord compression, delirium, brain, or leptomeningeal metastases [9, 10, 11, 12, 13].

According to the World Health Organization (WHO), more than 50% of the countries in the world are making efforts to provide treatment and palliative care for cancer patients. At the same time, many countries do not have a cancer control program [14]. Approximated cancer patients require more than one-quarter of global palliative care need [15]. Lack of enough communication enhance stress, decrease patient satisfaction, and decrease strictly following medical instructions, so adequate collection of data at a palliative care service enhance quality of patient care [16, 17, 18]. Early appearance of palliative care enhances quality of life, decreases therapeutic cost, and superior survival time. But, to provide convenient care to cancer patients, it is necessary to refer them to health services timely [19].

The core focus of palliative care also improves the care quality for the health care system [20, 21]. Besides improving physical symptoms, it will reduce emergency visits and reduces hospital admissions. For patients who have not taken palliative care at all or who came late to palliative care are more probably to receive invasive treatments, such as chemotherapy, and increase risk of death from treatment complications. Starting the palliative care at the time of diagnosis provides an adjuvant partnership for the treatment team and as the disease develops, the need for palliative care increases. That’s why it is suggested that palliative care be started in the first 8 weeks after the onset of the disease and the American Society of Oncology Guidelines also suggested that palliative care be initiated at the onset of cancer for some patients [22, 23, 24, 25].

That’s can improve all phases of the disease, it makes better decisions in the end-of-life care and potentially decreases health-care expenditures [26], and can generate consequential savings for the health system by decreasing hospitalization and interventions [27].

2. Palliative care for lung cancer patients

Lung cancer is considered as the main cause of cancer death among both men and women in the world [28]. The survival rate is estimated not more than 5-year [29] and the average survival patients who do not take any anti-neoplastic treatment is about 7 months, according to a meta-analysis of over 5000 patients [30]. The main reasons of death from lung cancer included complications of metastases, tumor burden, infection, thromboembolism, pulmonary hemorrhage, and diffuse alveolar damage. The final common attributor for most of these complications is respiratory failure. Both survivals, quality of life and symptoms are commonly worse for patients with end stage of the disease. Symptoms related to lung cancer can include pain, anorexia/cachexia, dyspnea, nausea, fatigue, confusion/delirium, and depression [31].

As pain is generally part of the reasons behind the suffering in these patients, beside psychological distress. Opioids are chief support that provides effective analgesia in cancer pain, such as morphine, which considered as is the most used opioid for moderate to severe pain. It can be used rectally or transdermally in patients who cannot take it orally [32]. Low-dose corticosteroids are also recommended for relieving pain from liver metastases, bony metastases, or neuropathic pain [33]. Anticonvulsants such as phenytoin, carbamazepine, and clonazepam are also helpful in treating that pain. Tricyclic antidepressants increase the effects of opioids and have analgesic properties [34].

Other symptoms that can develop from locally advanced NSCLC or lung cancer metastases are dyspnea and cough, these symptoms are disease-related complications, such as malignant effusions and airway obstruction. Therapeutic procedures with palliative aide can be helpful, such as pericardiocentesis with a pericardial drain/window, thoracentesis, or placement of pleural drain [35]. Other strategies for resolving airway obstruction include laser therapy, bronchoscopy, stent placement (endobronchial or vascular), or photodynamic therapy [36].

Morphine is usually used drug while recommendation of codeine or dihydrocodeine may be considered in dyspnea with lower intensity [37, 38]. Other opioids, including fentanyl and oxycodone, have been studied in this management, opioid mechanism of action is conveyed via opioid receptors of the cardio-respiratory system [39]. Benzodiazepines are also utilized as an adjunct, or as an alternative, to opioids for treating dyspnea which considered as a second or third choice in cases where morphine and non-pharmacological methods are not enough to control dyspnea [40]. Anticholinergic drugs such as hyoscyamine, scopolamine, atropine, and glycopyrrolate can be described to decrease excessive secretions [41, 42].

In 47–86% of lung cancer patients, cough is one of the most common symptoms of lung cancer. Pharmacotherapy includes administration of antitussive drugs and opioids. Oral corticosteroids that are taken for 14 days may resolve coughing result from direct infiltration of the bronchus by the tumor. As consequences of cough, gastro-intestinal reflux may occur; which may resolve with metoclopramide or domperidone. Dihydrocodeine, codeine also can be prescribed as antitussive opioid, codeine is usually in complex preparations with paracetamol. Constipation on the other hand is a complication of systematic administration of opioid, therefore prophylactic administration of laxatives is essential. Morphine or other strong opioids such as methadone are recommended for severe cough with pain in the chest, co-administration of more than one opioid is not appropriate. Mucolytic agents such as bromhexine and acetylcysteine that can be taken orally or by inhalation, but have limited use [43, 44].

Hemoptysis is a symptom that appears in about 20% of lung cancer patients. Pulmonary hemorrhage, which usually leads to death, is noticed in 3% of patients. The reasons behind hemoptysis include bronchiectasis, trauma after bronchoscopy, anticoagulation therapy, pulmonary embolism, fistulas, and others. Tranexamic acid and medications that support hemostasis such as vitamin K and antitussives are drugs that inhibit fibrinolysis that is used in adjunctive therapy at the end stage of disease. Also in the mentioned stage of disease mitigation procedures are used such as an appropriate position to forbid choking, taking anti-anxiety drugs (diazepam, midazolam) and using bed linen in dark colors [37, 43] in case of superior vena cava syndrome. The most seen symptoms include swelling of the face and congestion, upper chest and shoulders, shortness of breath, hoarseness, fainting on standing at the slope, dizziness, headache, and extension veins in the neck and the chest wall, corticosteroids such as dexamethasone are used as palliative treatment. Also, the use of heparin because of risk of thrombosis SVCS in the superior vena cava is reasonable [43, 45, 46].

Nutrition and appetite stimulants advising can be considered for patients with critical appetite and weight loss. Low-dose corticosteroids for appetite stimulation are unclear, but the benefit of it is often related to its antiemetic effect. Medications such as stimulants, antidepressants, steroids, and erythropoietin-stimulating agents have been assessed for treating fatigue but without definite evidence of benefit. The intervention studied for enhancing fatigue is exercise and physical activity [47, 48, 49].

3. Palliative care for ovarian cancer patients

Generally, it is called as the silent killer and it is the dominant gynecological cancer worldwide. Long-term survival of more than 5 years for those with advanced disease is realized in approximately 25% of patients [50, 51, 52]. Ovarian cancer’s early-stage signs and symptoms are usually vague and similar to other genitourinary or gastrointestinal illnesses. The recurrence is about 70% of ovarian cancer patients. Nearly all of the parenteral cytotoxic drugs indicated for recurrent ovarian cancer have massive side effects that decrease the therapeutic benefit and consequently patients’ acceptance of therapy. The less toxic alternative is altretamine which works to enhance the outcome of these patients.

Altretamine is an oral alkylating activity drug that has been prescribed for advanced ovarian carcinoma, it is prescribed for patients with recurrent ovarian cancer or who had undergone surgery and failed one or more chemotherapy regimen. It works as palliation for those with recurrent disease or as a maintenance drug to enhance and increase progression-free survival for these patients. Most benefit of altretamine is the decrease of physical and psychological discomfort came with the parenteral therapies and its oral use decreases the need for hospitalization [53, 54].

Besides altretamine, palliative therapy is used to minimize the symptoms of ovarian cancer. Women with ovarian cancer can have ascites. It can be very annoying but can be treated with paracentesis. It is a procedure where skin is numbed, a needle is inserted to withdraw the fluid. Another therapeutic option is a catheter which placed into the abdomen and the fluid can be eliminated as often as is needed. Bevacizumab (Avastin) can also help by slow fluid buildup, it is injected directly into the abdomen. These treatments can decrease symptoms, but rarely, might aide some women live longer. After all, their effects are temporary, and the cancer persists.

Another symptom is intestinal tract obstruction. That can cause nausea, vomiting, and abdominal pain, another procedure to allow the stomach juices to drain so that the digestive tract isn’t completely blocked, this is done by placing a tube through the skin and into the stomach [55, 56]. Other therapies to facilitate bowel movements include, drinking adequate fluids, and gentle exercise. To manage the symptoms of constipation some medications can be prescribed including ondansetron as anti-emitting, Miralax as laxatives, and steroids to reduce inflammation [57].

3.1 Pelvic or abdominal pain

At the beginning of ovarian cancer, pain can be easily ignored, hard to diagnose, or missed with other conditions. But, later in advance stage of ovarian cancer, it may cause a lot of pain and discomfort in the abdominal parts of your body. Over-the-counter (OTC) pain medications such as acetaminophen or anti-inflammatory pain relievers ibuprofen (Motrin, Advil). If your pain isn’t controlled by OTC medications, an opioid indicated in such cases, can help minimize stronger pain such as morphine, fentanyl patch, hydromorphone, and methadone. Also find an alternative therapy to decrease abdominal pain, for example, massage, try: acupuncture, relaxation techniques, such as guided imagery, meditation, and chiropractic treatment.

Ovarian cancer can expand and affect the urinary system. Its tumor can block the ureters that prevent the urine from reaching the bladder, which results in swelling, pain, and kidney damage if don’t treat. To relieve this pressure and pain, a special tube may utilize to drain the urine during cancer treatment. The tube can be placed inside the body to excrete urine from the kidney into the bladder, or outside of the body to excrete urine directly from the kidney.

Bloating and swelling can be seen at any stage of ovarian cancer. OTC remedies may not decrease this discomfort; octreotide may decrease these symptoms. Additionally, decreasing secondary bloating by staying away from carbonated beverages, processed foods, and gas-producing foods such as cabbage, beans, and broccoli [58, 59, 60, 61].

4. Palliative care for metastatic bone cancer patients

The skeletal system is the third most known site for cancer metastases, particularly in end stages of the disease. The presence of bone metastases leads to poorer diagnosis, decrease of survival and is usually associated with several complications, including spinal cord compression, severe bone pain, pathological fracture, and hypercalcemia, etc. [62, 63, 64, 65]. Nearly 60–84% of patients with late cancer experiences varying level of bone pain. Bon pain affects millions of patients worldwide, and approximately 450,000 patients in the USA alone annually [66, 67]. Generally, pain varies in severity depending on the stage of the disease. Most patients at the beginning of the disease experience infrequent dull aches, but as the disease advanced, pain becomes constant and increase in severity [68, 69].

Analgesic medications involve pain management with analgesics (non-opioid and opioid), adjuvants (corticosteroids, anticonvulsants), and bone-targeted therapies (NGF inhibitors; osteoclast inhibitors, such as denosumab and bisphosphonates). Radiotherapy (RT) is also used to reduce analgesic need, enhance the quality of life (QoL), also keep or improve skeletal function by minimizing the risk of metastatic spinal cord compression (mSCC) or pathological fractures [70].

Bone-seeking radiopharmaceuticals emitting-particles such as [223Ra] radium-dichloride at the top have been prescribed for bone-pain palliation. Beside [223Ra] a number of long-established and novel bone-seeking radiopharmaceuticals are prescribed for bone-pain palliation, including [89Sr] strontium-dichloride, [153Sm] samarium, [186Re] rhenium, [188Re] rhenium, [177Lu] lutetium, and [166Ho] holmium labeled [71, 72, 73, 74, 75, 76]. the control of painful bone metastases is still a challenging problem. Bone-pain palliation with radiopharmaceuticals emitting-particles been utilized for decades, demonstrate an acceptable result. [223Ra] Radium shows higher advantages impact on survival over other radiopharmaceuticals; at the same time, still the expensive [223Ra] radium is not generally available [77].

5. Palliative care for pancreatic cancer patients

Pancreatic cancer is the twelfth most common cancer in the world and the seventh leading cause of cancer death. It has a poor survival rate, it mortality rate about 4.0% of all cancer deaths [78, 79, 80]. Now a day surgical resection is the only choice for treatment, however, only 20% of pancreatic cancer is surgically removable at the time of diagnosis [81, 82, 83]. The maximum survival rates are 22–26 months in patients who are undergoing surgical resection and taking adjuvant therapy resect able to improve survival [84, 85, 86, 87] latest studies evaluating the effect of neoadjuvant therapy on highly picked patients with resect able disease have led to median survival life about 44 months in patients with R0 resection, node-negative disease [88, 89, 90].

5.1 Planned operative and endoscopic palliation

Choledochojejunostomy or Roux-en-Y hepatico was surgical palliation that was most commonly done. But its performance fell out of favor as a result of a high probability of cystic duct, gastric outlet, or duodenal obstruction by the tumor over time, as well as the likelihood of bile reflux into the stomach. The placing of endoscopic biliary stents throughout endoscopic retrograde cholangiopancreatography (ERCP) is the favorite method for palliation of obstructive jaundice in patients with metastatic or unresectable pancreatic cancer. Development in endoscopic technology results in successful stent placement in more than 90% of patients during ERCP with the same efficacy, but less mortality and morbidity in comparison with surgical palliation with biliary-enteric bypass. After all, studies still present the majority of patients who are stented have an enhancement in quality of life, even with higher rates of recurrence [91, 92, 93]. Prophylactic gastrojejunostomy was associated with a diminished incidence of late GOO (gastric outlet obstruction). It was also indicated in patients with unresectable periampullary cancer that undergo exploratory laparotomy [94, 95, 96].

5.2 Endoscopic palliation

Treatment of gastric outlet obstruction can be done endoscopically, with placing of large self-expanding stents which are successful in 92–100% of cases permitting patients to take back oral intake in 24 hours in 73–93% of patients. Even though patients can control their own drink liquids and salivary secretions, stent obstruction usually occurs with solid food [91, 93].

5.3 Thromboembolic disease

Pancreatic cancer patients have one of the highest frequencies of pulmonary embolism (PE) or deep venous thrombosis (DVT) with incidence rates between 17 and 57%. Anticoagulation drugs with low-molecular-weight heparin or a direct oral anticoagulant are useful in patients who develop a VTE. Many studies estimate this risk, showing a 10–25% risk of VTE, with minimization to 5–10% with thromboprophylaxis but no effect on survival. Treatment includes treatment with low weight molecular heparin (LWMH), unfractionated heparin, or oral anticoagulation [97].

6. Palliative care for oral cancer patients

Patients may experience oral side effects as a result of disease or medications. Anti-cancer medications have acute and long-term adverse effects on healthy tissue. The epithelium of the oral mucosa can be affected by most therapeutic agents that may cause xerostomia, mucositis, and taste alterations [98, 99, 100, 101, 102, 103, 104, 105].

Beside this side effect, patients in the end stage of the disease, perhaps as a result of their weakness, oral symptoms are one of their highest sources of discomfort. Symptoms involve oral candidiasis, angular cheilitis, oral pain, mucositis, denture stomatitis, dysphagia, ulceration, taste disorders, oral infection, halitosis, and dry mouth, which is the most familiar oral symptom. The causes behind oral problems are several, such as general weakness from disease or its medications; previous cancer treatment, such as chemotherapy and radiotherapy; dehydration; and the decrease the ability of water or food intake; their physical condition may decay because of oral symptoms, which lead to inability of food intake and dehydration [106, 107, 108, 109].

7. Oral care palliative care protocol

At the beginning of oral care, a facial massage of the masseter muscle and salivary glands. An oral moisture jelly and moisture spray were utilized for enhancing mucosal moisture and for protecting the mucosa. Also, a soft dental brush was used to remove plaque and debris on the teeth. Then, oral foam sticks were utilized for mucosa cleansing [110].

Palliative treatment for squamous cell carcinoma treatment included mono-chemotherapy with the administration of cetuximab. The side effects of cetuximab are manageable. The common reactions are mostly cutaneous, with the appearance of acne, dryness, itching, and peeling on the skin [111]. Corticosteroids such as prednisone are usually administrated with the cetuximab treatment to minimize the previously mentioned adverse effects. Nonetheless, the repeated use of this medication may cause other disturbances, such as osteoporosis [112].

7.1 Pain management for oral cancer patients

Cancer pain may result from direct invasion cell of cancer into the nerve or bone tissue in the end stages of oral cancer and its management is critical issue [113]. Opioid analgesics are usually prescribed for controlling oral cancer-related pain. In spite of high dosages of opioids are prescribed, high level of cancer pain is usually poorly controlled. Switching is often necessary due to different side effects or tolerance of opioids. Methadone has been widely prescribed to manage oral pain because of its exclusive properties (e.g., long duration of action strong, high bioavailability, and analgesic effect) [114].

7.2 Xerostomia prevention therapies

Xerostomia is one of common adverse effects of radiation therapy on salivary glands. Radiation exposure may change saliva volume, consistency, and its pH. The inadequate saliva can decrease the quality of life as the patient cannot carry forward with his routine diet, which came with difficulty in swallowing and dysguesia that can lead to nutrition deficiency. Several managements are utilized to decrease xerostomia such as water-soluble lubricants that must be applied thinly over the oral mucosal surfaces to lubricate the oral tissues. Mouth rinses that contain alcohol should not be used in such cases as they will increase mouth dryness.

Salivary stimulation agents should be advised, like vitamin C and citric acids, sugar free topical agents malic acid that used topically can stimulate saliva, though, their low pH enhances demineralization of teeth. Salivary stimulation agent proves to be beneficial for the xerostomia patient and should be taken before eating to enhance swallowing. The two most common pharmacologic medications prescribed to stimulate salivary secretion are cholinergic agonists such as cevimiline and pilocarpine, treatment continues for 12 weeks of uninterrupted therapy is recommended. These drugs are contraindicated in patients with narrow-angle glaucoma, acute iritis, and asthmatic patient [115, 116].

Bethanechol chloride cholinergic agonist that its works in contrast to acetylcholine, bethanechol has more prolonged effects as a result of resistant to destruction by cholinesterase. Its mechanism of action is similar to pilocarpine, stimulating the parasympathetic nervous system. It acts more specifically on the muscarinic receptors, not acting on α/β-adrenergic receptors, as pilocarpine does [117]. These medications work as systemic stimulants of salivary gland acting on the parasympathetic nervous system. The response to enhance salivation is depending on the residual number of functional acinar cells [118].

Herbal medicines were also found to enhance salivary function and to decrease the severity of mouth dryness in cancer patients [119]. In spite of several RCTs of acupuncture as a management for dry mouth have been stated to date, its cumulative evidence for its effectiveness has not been systematically estimatted [120]. An organic thiophosphate is amifostine that can protect cells from radiation distruction by scavenging oxygen-derived free radicals. The prescription of amifostine is very controversial because of its toxicity, cost, and compromised tumor control, in spite of all previous disadvantages, it is considered the only drug approved by FDA for xerostomia result from radioprotection [121]. The prophylactic use of systemic sialogogues for radiation-induced xerostomia is widely reported in the literature [122].

7.3 Management of taste loss and candidiasis

Chemotherapy and radiotherapy for oral cancer can change or reduce taste function as a result of the outer surface of taste cells and microvilli and damage that leads to limitation in food intake and weight loss as consequences. Taste loss is generally temporary and returns gradually to normal levels within 1 year after taking radiotherapy but sometimes it may last for 5 years [123]. High incidence of non-Candida albicans infection has been estimated in patients with end stage of cancer. The untreated colonized Candida can lead to disseminated disease that can end with morbidity and mortality. Fluconazole is considered as one of the first-line medications prescribed for management of oral candidiasis in cancer patients. Amphotericin B and newer drugs like echinocandins are also used for invasive Candida infections [124, 125].

Taste is very important for life; it manages food intake and provides pleasure feeling from eating. The taste regulates digestion, absorption, and storage of nutrient perception by activation neuronal pathways [126]. Alteration or taste dysfunction (dysgeusia) may decrease the quality of life by affecting and psychological well-being, appetite, and body weight. Several factors can affect taste perception, such as lesions in the oral mucosa, medication, prolonged exposure to radiation and chemotherapy, smoking, nutrition, chronic hepatitis, aging, renal impairment, and disorder in hormonal secretions [127]. Zinc supplements can be useful for patients receiving chemotherapy. Zinc protected the cancer patients from taste alteration [128] other form, a zinc containing polaprezinc that can also protect against taste disorder [129]. Amifostine, protect salivary gland normal tissues from damage by chemotherapy and radiation [130] thus leading to improvement of xerostomia that may cause taste alterations [131].

7.4 Osteoradionecrosis

Osteoradionecrosis is a complication result from radiation therapy to the head and neck that results in bone death, its side effect includes neuropathic pain [132]. Hyperbaric oxygen (HBO) therapy companied surgery can be used in the management of osteoradionecrosis, HBO enhances tissue oxygenation through control of infection, angiogenesis, predominantly through stimulate bacterial killing fungi, macrophages, and production of bactericidal free radicals [133, 134]. Other treatment modalities—Ultrasound has reported to stimulate tissue regeneration by enhancing blood flow in chronically ischemic muscles, protein synthesis and cure of ischaemic varicose ulcers. Pentoxifylline and calcitonin also have been used successfully to treat ORN [135].

7.5 Psychological and other factors

Antiemetics such as selective serotonin type 3 receptor (5HT3) antagonists (e.g., ondansetron, granisetron), neurokinin 1 receptor antagonists (e.g., fosaprepitant, aprepitant), and synthetic cannabinoids (e.g., nabilone) are licensed for use in chemotherapy-induced nausea and vomiting (CINV) [136]. In response to oral cancer treatment there may be changes in patients including their ability to swallow, speech, taste deprivation of sleep or metabolic disorders, and alterations in appearance. These changes can be emotionally harmful to the patient. This required psychiatric interventions in such patients.

8. Palliative care in head and neck cancer

Cancer of head and neck is the sixth most common cancer, the overall survival rate is 5-year that has ranged from 40 to 65%, affected by several factors such as co-morbidities and advanced-stage disease presentation [137, 138].

8.1 Surgical palliation

Incurable end-stage head and neck cancer lead to upsetting symptoms such as pain, bleeding, swallowing, and breathing difficulty. Patients may try to stay active and self-caring while trying to adapt to these symptoms. Surgery can decrease primary tumor bulk, decrease pain and bleeding, enhance swallowing, nutrition and airway, many evidence is available to estimate the surgical benefit in such cases. Also, an endovascular technique, involving embolization and vessel stenting, can help by controlling bleeding symptoms result from major vascular erosion. However, benzodiazepines are rapid-acting sedatives that reduce the flow of blood with direct pressure that administrated when patient succumbs rapidly in case of acute hemorrhage from carotid “blow-out.” Whilst success may achieve with swift surgical intervention, continuous verbal support to the patient is a key to control and decrease anxiety. Besides benzodiazepines, use of bisphosphonates aid pain control of bone pain.

8.2 Pain

Pain is very familiar symptom that affects patients at any stage of cancer. It can be immediate or persistent lifelong. Analgesic use is the preferred one based on the WHO. Choice of formulation depends on patient conditions, if he can swallow. Persist vomiting has a nasogastric or gastrostomy tube. In case of somatic pain, oral morphine is the first choice strong opioid such as Oramorph™ solution or Sevredol™ tablet (e.g., MST Continus™) or capsules (e.g., Zomorph™) and suspension (e.g., MST suspension™) or opened capsules (e.g., Zomorph™).

In case of continuous vomiting, subcutaneous (SC) infusion of morphine or diamorphine can be prescribed such as diamorphine, transdermal preparations of fentanyl. Alternatively, new formulations of sublingual, buccal, or intranasal fentanyl may have a role in specific situations. Oxycodone may act as an alternative to morphine when there is intolerance, specifically dysphoria, the injected form of hydromorphone is useful. Liquid form of methadone in can be very useful, because of its rapidity in onset and long acting.

Neuropathic pain is a very common feature of the disease and also can result from treatment, specially radiation. Some medications can be referred to as adjuvants such as a tricyclic antidepressants (e.g., amitriptyline), anticonvulsants (gabapentin and pregabalin). Gabapentin in some cases opened and administered via the gastrostomy tube. Also carbamazepine, sodium valproate also can be used. Clonazepam is sometimes useful. Methadone and ketamine are useful, but only in specific settings. In case of visceral pain, if the pain is poorly sensitive to opioids, adjuvants should be administrated early, for example, pain due to nerve compression or metastatic disease in the liver cab is controlled with dexamethasone (4–8 mg daily). Interventional pain techniques may be very useful when systemic treatments fail or in case the patient is intolerant of the significant doses of analgesics combination.

In case of mucosal pain topical agents can be used such as chlorhexidine, sulcralfate, benzydamine, steroids, and topical local anaesthetics such as lignocaine. High number of patients who are enterally fed suffer from nausea and vomiting, so there is usually a need for injectable anti-emetics—continuous infusions, subcutaneous (SC), or boluses. Enteral feeding has its own challenge; prokinetic drugs like metoclopramide or domperidone may be utilized to establish the best function.

8.3 Constipation

Constipation develops in 50% of cancer patients as a result of decreased physical activity, dehydration, hypercalcemia, hypothyroidism, and some kind of medications, specially opioids and anticholinergic drugs. Laxatives can be stated once opioid medication is initiated. Laxative agents include bisacodyl, senna, lactulose, magnesium hydroxide, docusate, movicol, laxido. If constipation develops it can lead to nausea and vomiting and in the severe situations pseudo-obstruction. If rectal examination reveals hard stool, then the use of suppositories and enemas can be helpful.

8.4 Anxiety

Benzodiazepines are the main treatment of anxiety. Such as diazepam, lorazepam, and midazolam. However, the limiting point is developing tolerance very fast; so they are useful only for short-term control of episodes of anxiety.

8.5 Delirium

Delirium is a neuropsychiatric condition that is may increase incidence of morbidity and mortality in patients with end stage disease, which profoundly impacts the patients, their families, and their caregivers [139]. As a cause of confusion can result from number of organic causes such as metabolic disturbance, respiratory failure, infection, dehydration, urinary retention, constipation, brain metastases, and other causes. Common causes are administered drugs specially opioids.

Usually, delirium is controlled with haloperidol or levomepromazine where sedation is required for managing paranoia. In some conditions, like irreversible agitation or delirium in end stage patients, benzodiazepines and antipsychotics are required to administered together using a syringe driver secretions [9]. The most common used antipsychotic drugs in delirium patients are phenothiazines (e.g., chlorpromazine), butyrophenones (e.g., haloperidol), second-generation antipsychotics (e.g., olanzapine, risperidone, quetiapine, and ziprasidone), and third-generation antipsychotics (e.g., aripiprazole). In spite of little supporting data, there is no approved medication for delirium, antipsychotics are widely used but still the role of antipsychotics remains uncertain [140, 141, 142, 143, 144]. Excess secretions at the end stage of cancer are treated using anticholinergic medication to support this end-of-life phase. Also, there are three widely used antimuscarinic drugs that can be prescribed for excess secretion which include hyoscine hydrobomide, hyoscine butylbromide, and glycopyrronium [9].

9. Palliative care for colorectal cancer patients

Colorectal cancer is the third most common malignant disease about 1.85 million of new cases a year around the world and nearly 10.2% of total [145]. Surgical resection may consider as good palliation of symptoms and prevent harmful complications consequences [146].

10. Palliative care for bladder cancer patients

Bladder cancer is the ninth most common malignancy in the world [147]. The 5-year survival for bladder cancer is 76.9%, however, metastatic disease 5-year survival rate is only 5.5% [148]. It is mainly seen in elderly people [149]. Bladder cancer can cause persistent and disabling pain in patients [150] pelvic pain is one of the major end-of-life complications in people suffering from bladder cancer [151]. The pain control in some cases was adequate with fentanyl patches [152] bleeding can also arise from the bladder cancer, or as a result of radiation or cyclophosphamide, infection can also worsen bleeding. Patients with severe haematuria can be treated with palliative TURBT, tranexamic acid, palliative radiotherapy, embolisation, palliative chemotherapy, and urinary diversion [153].

11. Palliative care for breast cancer patients

Breast cancer is the most common cancer among women worldwide and the most common cause of cancer death in women. About 23% of the 1.1 million female with cancers newly diagnosed every year. And about one-fifth will survive for 5 years; American Cancer Society estimated that breast cancer is the second only to lung cancer as a cause of cancer death in women [154, 155, 156, 157, 158, 159].

11.1 Pain

In general, the major causes of cancer-related pain in breast cancer women are bone metastases [160, 161]. Opioid analgesic medications can be submitted for patients with strong pain, in the case of neuropathic patient, patients may get benefit by combined analgesic with an agent with special efficacy for this mechanism of pain like tricyclic, SNRI, and/or an anticonvulsant. Radiotherapy may be also important in case of bone metastases for patients with poorly controlled pain [161, 162, 163].

11.2 Breathlessness (dyspnea)

Patients with breast cancer usually suffer from breathlessness; there are many causes of dyspnea and for its management, non-pharmacological and pharmacological approaches can be used [39]. Sitting the patient in upright position, use of bedside relaxation techniques, and accelerating air flow over the face using a fan or open window, are all helpful. Also, large symptomatic pericardial or pleural effusions should be drained. Oxygen supplementation can decrease dyspnea for patients with hypoxemia. Opioids are also approved for symptomatic therapy for dyspnea at the end stage of the disease [164].

11.3 Fatigue

Fatigue is the most common cause of distress to the patients. Restoration of energy strategies involved taking adequate nutrition and rest, decreasing stress can be done by several techniques like meditation or relaxation. Physical exercise proved to be useful in many clinical trials [165]. Fatigue patient’s anemia with a hemoglobin of lower than 8 g/dL may require blood transfusion to maintain a hemoglobin level between 10 and 12 g/dL. Some studies mentioned that methylphenidate or modafanil can be useful for patient with fatigue symptoms but till now there are some limited data about its benefits regarding fatigue [166]. Steroids may have a role in short-term control or decease of fatigue for a patient who needs to be in his optimal alertness for an important family event or special occasion, but there is no benefit in long-term fatigue management [164].

11.4 Depression

Patient having cancer can be depressed experience, its incidence lower than anxiety. Although, it can be underreported by patients [167, 168]. Depression in cancer patients usually needs combining antidepressant medications, supportive psychotherapy, and cognitive-behavioral techniques [169]. Antidepressant is the main management for cancer patients with severe depressive symptoms that should be accompanied by psychotherapy by a professional therapist. That include selective serotonin re-uptake inhibitors (e.g., fluoxetine, sertraline, paroxetine, citalopram, and fluvoxamine), serotonin-norepinephrine reuptake inhibitor (e.g., venlaflaxine), and the serotonin-2 antagonists’/serotonin reuptake inhibitors, nefazodone and trazodone, and psychostimulants (e.g., methylphenidate) [170].

However, home palliative care enhances care and rehabilitation, its practiced by the interdisciplinary team help the patient to stay at home, in familiar environment, where relaxation and comfort not founded in the environment of the hospital. Necessary equipment is brought home to conduct therapy, such as an infusion pump. From time to time, qualified medical personnel should visit the patients allow efficient communications with patients and their families, manage the therapy, checking bedsores, and explain proceedings in the case of unexpected health hazards. For patients who cannot be medically managed at home, staying in inpatient care units for control or alleviate the symptoms is not adequate or sufficient [171].

12. Conclusion

This study summarized different kinds of palliative therapies for different types of cancer that improves the wellbeing of patients with life-limiting condition. It supports their families by identification patient needs, correct assessment and use of therapeutics for control health-related concerns such as management of physical issues (reliving patient from pain) and dealing with psychosocial, emotional state. Early palliative care prolongs life by decreasing morbidity and improved quality of life by using different strategies which include medication, surgical, nutrition, and home palliative care. It also reduces the load, strain of hospital related stresses and unnecessary hospital visits, in addition to decreasing hospital and health care cost.