First author Publ. year Location Inclusion Criteria Exclusion Criteria Active group Comparison group Duration/
Castro et al. 2003 [38] 2003 North America Histologically confirmed recurrent, refractory HNSCC. Tumours > 0.5 cm3 and > 20 cm3. Prior course of cancer therapy NYHAC III or IV cardiovascular symptoms; cardiac arrhythmias; extracranial carotid vascular disease; known hypersensitivity to components. Tumours with immediate risk of haemorrhage, embolization, or uncontrolled local infection at the treatment site. Fibrotic lesions, and tumours that directly involving or threatening carotid artery CDDP/epi gel injected into the tumour at 0.25 ml gel/cm3 of tumour volume Placebo gel containing 0.9% NaCl injected into target tumour, similar dose to active gel 5 ½ years
Georgiou et al. 2000 [39] 2000 Greece Final stage of the disease, suffered pain uncontrolled by oral morphine Not mentioned Cervical epidural catheter inserted and bolus of morphine given Thoracic epidural catheter inserted and bolus of morphine given 10 days
Jovic et al. 2008. [40] 2008 Serbia Operations for HNC Preoperative analgesics, allergy to NSAIDS, history of peptic ulcer and coagulopathy Ketoprofen 100 mg IV every 8 hours for the first 3 - 5 days 2.5 mg IV Metamizole every 8 hours for the first 3 - 5 days 3 days
McNeely et al. 2004 [47] 2004 Canada HNSCC managed by definitive surgical resection also metastatic spread. Radical neck dissection and variants. Medical diagnosis of shoulder dysfunction caused by spinal accessory neurapraxiaeurectomy and evidence of trapezius dysfunction Reported comorbid shoulder pathology and/or had a medical illness or psychiatric illness. No distant mets, no evidence of residual cancer in the neck PRET- exercise 3 times a week. Exercises individualized to suit each subject. 6 exercises in total Standard care exercise program 12 weeks
McNeely et al. 2008 [27] 2008 Canada HNSCC for surgical treatment, radical neck dissection, modified radical neck dissection, other variants of selective neck dissection; Karnofsky performance status ≥ 60%. No evidence of residual cancer in the neck and no distant metastasis; completion of adjuvant HNC treatment. Symptoms of shoulder dysfunction from spinal accessory nerve damage Shoulder or neck pathology unrelated to cancer treatment, comorbid medical illness or psychiatric illness preventing completion. PRET- 2 sets of 10 - 15 repetitions of 5 - 8 exercises TP = supervised active and passive ROM, stretching postural and strengthening exercises with light weights and elastic resistance bands. 12 weeks
Pfister et al. 2010 [48] 2010 North America Neck dissection; expressed com- plaints of pain and/or dysfunction in the neck and/or shoulders from neck dissection; > 3 months since neck dissection and radiation; only moderate and severe pain/ dysfunction Received acupuncture and oriental medicine Acupuncture once a week for 4 weeks Needles inserted 0.25 to 0.5 inches and retained for 30 minutes. Physical therapy, analgesics and anti-inflammatories 4 weeks
Plantevin et al. 2007 [41] 2007 France Lateral transmandibular pharyngectomy or partial glossectomy under GA Severe renal/hepatic impairment, heart failure, chronic respiratory disease, contraindications to regional anaesthesia, inability to understand PCA, ASA physical classification status > III, age < 18 years Preoperatively MNB Deep s.c. injection of normal saline pre-operatively 48 hours post surgery
Roussier et al. 2006 [42] 2006 France Undergoing elective laryngeal surgery for cancer with tracheostomy Chronic pain or opioid dependence, contraindications to cervical epidural catheter, inability to understand PCA, chronic respiratory impairment, ASA physical classification status IV or V, age < 18 years Patient controlled epidural Fentanyl, loading dose of Fentanyl 1.5 mg kg-1, maintenance dose 25 mg lockout interval 10 min Patient Controlled IV Fentanyl, PCA identical with epidural pump 48 hours post surgery
Saxena et al. 1994 [43] 1994 India Continuous pain at tumour site, NRS > 3 Bleeding from any site, surgery in preceding 10 days, renal/hepatic impairment, intermittent pain, communication difficulties Piroxicam 20 mg 12 hourly ASA 500 mg 6 hourly 4 days
Singhal et al. 2006 [44] 2006 India ASA status I and II, age range 25 - 60 years. For oral cancer surgery with PMMF reconstruction Chronic pain, chronic opioid use, drug/alcohol abuse, chronic headache, backache, peripheral neuropathy, low platelet count (< 100 000/mm3), deranged bleeding/clotting time. 3 mg of Morphine and 10 ml Saline through epidural in T8/T9 interspace every 12 hours 3 mg Morphine intravenously when VAS score > 30 48 hours post surgery to discharge
Werner et al. 2002 [45] 2002 Europe and Israel Histologically confirmed, recurrent or refractory, primary or metastatic HNSCC. Only problematic tumours NYHAC III or IV cardiovascular symptoms, history of cardiac arrhythmia, head and neck tumour not of squamous cell origin, history of extracranial carotid vascular disease. CDDP/epi gel injected into target tumour, at 0.25 ml cm-3 of treated tumour volume. Placebo gel containing 0.9% Saline injected into target tumour, at similar dose to active gel. 6 months
Wittekindt et al. 2006 [46] 2006 Germany Tumor recurrence-free survival of 18 months or longer Neurological diseases causing chronic pain in the neck and shoulder 0.1 mL BtxA solution injected per site, 10 MU per site in low-dose group 0.1 mL BtxA solution injected per site, 20 MU per site in high-dose group 28 days
Yagi et al. 1997 [35] 1997 Japan Postoperative patients for head and neck cancer surgery No information IV Fentanyl at a rate of 10 mg per hour. 20 mg Piroxicam after anaesthesia every 24 hours for 2 days Received analgesics: Pentazocine i.m, suppository Diclofenac sodium judged by a surgeon when patient complained of pain 48 hours

ASA = acetylsalicylic acid; MNB = mandibular nerve block; CDDP/epi gel = intratumoral cisplatin/epinephrine injectable gel; PCA = patient controlled analgesia; HNC = head and neck cancer; VAS = Visual Analogue Scale; NRS = Numerical Rating Scale; PMMF = pectoralis major myocutaneous flap; IV = intravenous; s.c. = control subcutaneous; GA = general anaesthesia; ROM = range of motion; HNSCC = squamous cell carcinoma of the head and neck; PRET = progressive resistance exercise training; TP = exercise protocol.