**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

*Palliative Care Therapies DOI: http://dx.doi.org/10.5772/intechopen.105220*

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.

*Palliative Care Therapies DOI: http://dx.doi.org/10.5772/intechopen.105220*

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 [140–144]. 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].
