Article of the Month

Reviewed by: Carla Ripamonti, MD (Italy)

Effect of topical morphine for mucositis-associated pain following concomitant chemo-radiotherapy for head and neck cancer.

Authors: Cerchietti L.C.A., Navigante A.H., Bonomi M.R., et al.

Journal: Cancer 2002; 95: 2230-6

Mucositis-associated pain following concomitant chemo-radiotherapy for head & neck cancer is a serious clinical problem that impairs nutrition and the quality of life of patients.

The intensity of the pain is often severe and the control of it may require high doses of opioid analgesics or the administration of opioids via the intravenous route.

Pre-clinical studies have shown that peripheral opioid receptors begin to appear in tissue minutes to hours after the initiation of an inflammatory reaction. The analgesic efficacy of peripheral acting opioids also increases linearly with the duration of the inflammation (Stein C. Anesth Analg, 1993; Schaefer M et al. Eur J Pharmac, 1995; Antonijevic I et al. J Neurosci, 1995).  With this in mind, this prospective, randomized study was carried out in patients with painful oral mucositis (WHO grade 2 or higher), a KPS of at least 60%, and MMSE of at least 24/30 following chemo-radiotherapy for head and neck cancer.  The aim of the study was to compare the analgesic efficacy, ability to maintain oral intake and the adverse effects of two different topical mouth washes.

Fourteen patients were treated with morphine mouth wash (MO) and 12 patients were treated with a magic mouth wash (MG) mixture.  The patients were assessed by means of  a numerical rating scale NRS (0-10), VRS (worst possible, severe, moderate, low and none) and a functional impairment scale (FIS) (1= able to eat solid foods, 2= able to eat soft foods; 3 = able to eat liquids, 4= oral alimentation impossible). The patients were evaluated until there was total alleviation of mouth pain (NRS) ≤1; VRS (low or none) and recovery of oral function (FIS = 1 or 2).

The MO group were treated with an oral rinse consisting of 15 mL of a 2% morphine solution. The MG group used an oral rinse mixture of 5 mL of magnesium aluminium hydroxide, 5mL of 2% viscous lidocaine and 5 mL (12.5 mg ) of diphenhydramine. In both cases, oral rinses were administered every 3 hours six times a day. The rinse was held in the mouth for 2 minutes. In patients who had dentures, they were removed before the rinse. Analgesic drugs were also administered as needed.

The primary endpoints of the study were to evaluate:

1. the number of days of pain > 5 and/or worst possible or severe pain,
2. the intensity of pain,
3. the number of days of severe functional impairment.

The results of this study showed that there were 3.5 fewer days of severe pain in the MO group compared with the MG group (p= 0.032); the intensity of the oral pain was also significantly lower in the MO group compared with the MG group (p= 0.038), and the duration of severe functional impairment was 1.85 days ± 1.53  (mean days ± SD) in the MO group compared to 7.67 days ± 4.3 in the MG group (p= 0.017).

Sixty-seven percent of MG group patients required supplementary analgesia compared with only 21% of MO group (p = 0.019).  No patient in the MO group required strong opioid analgesics (p = 0.088). Patients in the MG group reported more local side effects but there were no observed difference in body weight changes in the two groups.

Why I chose this article.

The authors were able to demonstrate what we have observed in our daily clinical practice. Compared to magic mouthwash (MG), oral morphine mouthwash (MO) administered 4-5 times a day is a simple, safe and effective treatment to reduce the intensity and duration of pain in the oral cavity in the patients with painful mucositis.  Moreover, although it was not considered by the authors, the cost of MO is significantly less than that of MG.

The results of this study when applied in clinical practice should be able to decrease suffering and increase the quality of life of cancer patients with chemo-radiotherapy induced painful oral mucositis. In addition, the treatment can be prescribed for patients at home and therefore should reduce hospitalization time needed to control this symptom.

Reviewer:
Carla Ripamonti, MD
(Italy)

Dr. Carla Ripamonti is also a member of the IAHPC Board of Directors
http://www.hospicecare.com/Bio/c_ripamonti.htm

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