• Head and Neck Cancer Disease Site Group. Hodson DI, Haines T, Berry M. Symptomatic treatment of radiation-induced xerostomia in head and neck cancer patients [full report]. Toronto (ON): Cancer Care Ontario (CCO); 2004 Mar [online update]. 11 p. (Practice guideline report; no. 5-5). [29 references]

Radiation-induced xerostomia in head and neck cancer

Assessment of Therapeutic Effectiveness
Treatment

Oncology
Otolaryngology
Radiation Oncology

Physicians

To make recommendations regarding optimum symptomatic management for xerostomic patients following conventionally fractionated radical radiotherapy for head and neck cancer

Adult head and neck cancer patients with symptomatic xerostomia following radiation therapy

1. Pilocarpine (tablets or oral solution)
2. Other treatments for radiation-induced xerostomia considered but not recommended: artificial saliva, chewing gum, lozenges, classical acupuncture, Glandosane spray, sodium bicarbonate 1%, xialine, cevimeline, humidification, bethanechol, oral gel, and toothpaste

The primary outcome of interest is improvement in patient symptomatology. Toxicity was also considered.

Hand-searches of Published Literature (Primary Sources)
Hand-searches of Published Literature (Secondary Sources)
Searches of Electronic Databases

Original 1998 Guideline

MEDLINE and CANCERLIT searches were performed for the period 1980 to October 1998. Search terms included "radiation", "treatment", "xerostomia", "prevention", "management", "clinical trial", "meta-analysis", and "practice guideline(s)". To locate recent articles that had not yet been indexed in MEDLINE, PREMEDLINE was searched up to October 1998, using the text words "xerostomia" and "radiation." Ongoing trials (actively recruiting or recently closed) were identified from the Physician Data Query (PDQ) database. Articles identified by the search or cited in relevant papers or reviews were retrieved and reviewed.

March 2004 Update

The original literature search has been updated using MEDLINE (through March 2004), EMBASE (through March 2004), the Cochrane Library (Issue 1, 2004), the Physician Data Query database, the Canadian Medical Association Infobase, and the National Guideline Clearinghouse, as well as abstracts published in the proceedings of the meetings of the American Society of Clinical Oncology (1995–2003), the American Society for Therapeutic Radiology and Oncology (2000–2003), and the European Society for Medical Oncology (1998, 2000, 2002). Article bibliographies and personal files were also searched to March 2004 for evidence relevant to this practice guideline report.

Inclusion Criteria

Articles were selected for inclusion in this systematic review of the evidence if they met the following criteria:

1. Randomized controlled trials (RCTs) that measured symptomatic relief of radiation-induced xerostomia in head and neck cancer
2. English language publications

Original 1998 Guideline

Of 65 articles identified by the searches, 11 were deemed appropriate for in-depth review. Five of these were general management overviews. No published guidelines or meta-analyses were found. Five randomized trials (four placebo-controlled trials of oral pilocarpine and one trial comparing artificial saliva with a mouthwash containing pilocarpine) met inclusion criteria. One cohort study was found which addressed some of the Disease Site Group member's concerns about long-term treatment. The four placebo-controlled trials of oral pilocarpine were included in this practice guideline report.

March 2004 Update

An update of the literature identified one systematic review, a paper integrating results of two previously identified trials, ten fully published new randomized trials, and one new trial published as an abstract.

Expert Consensus (Committee)

Not applicable

Meta-Analysis of Randomized Controlled Trials
Systematic Review with Evidence Tables

The guideline report was developed by the Cancer Care Ontario Practice Guidelines Initiative (CCOPGI) using the methodology of the Practice Guidelines Development Cycle (see companion document by Browman et al). Evidence was selected and reviewed by two members of the CCOPGI’s Head and Neck Cancer Disease Site Group and methodologists.

Original 1998 Guideline

Synthesizing the evidence: To obtain a more precise overall estimate of the effects of treatment, results were pooled across trials where possible and appropriate using Metaanalyst^0.988 software provided by Dr. Joseph Lau (Boston, MA). Pooled results are expressed as risk ratios (RR, the proportion of patients in the treated group reporting improvement over the proportion in the placebo group) with 95% confidence intervals (CI). In this case, risk ratios greater than 1.0 favour the active treatment group. Data were analysed using the more conservative random-effects model. All significance tests are two-sided.

March 2004 Update

The information above remains current.

Expert Consensus

Original 1998 Guideline

The practice guideline was initially prepared by two members of the Hamilton Regional Cancer Centre Head and Neck Cancer Disease Site Group (DSG). The report was discussed by the Provincial Head and Neck Cancer DSG, and the amended report circulated for critique and comment.

Issues discussed by the Provincial Head and Neck Cancer DSG included the ideal time to start treatment with pilocarpine, the duration of treatment, the duration of benefit, toxicity, availability and cost, and the target patient population. The DSG members agreed that the ideal time to start treatment with pilocarpine and the duration of treatment remain undefined.

March 2004 Update

The information above remains current.

Not applicable

A formal cost analysis was not performed and published cost analyses were not reviewed.

External Peer Review
Internal Peer Review

Original 1998 Guideline

Practitioner feedback was obtained through a mailed survey of 41 practitioners in Ontario (17 radiation oncologists, 7 medical oncologists, 9 surgeons, and 8 otolaryngologists) consisting of nine questions asking for ratings on the quality of draft recommendations and whether the draft recommendations should serve as a practice guideline. Written comments were invited. Follow-up reminders were at two weeks (postcard) and four weeks (complete package mailed again). The Head and Neck Cancer Disease Site Group reviewed the results of the survey. Twenty-four (59%) surveys were returned.

Final approval of the original guideline report was obtained from the Practice Guidelines Coordinating Committee.

March 2004 Update

The guideline authors have reviewed the new evidence from trials of pilocarpine and have concluded that it is consistent with evidence used to inform the original guideline recommendations. No changes to the recommendations are warranted at this time. The remaining randomized trials of novel agents or aids have failed to demonstrate a meaningful difference between treatment and control arms. Again, no changes to the recommendations are warranted at this time.

• For head and neck cancer patients with symptomatic xerostomia following radiation therapy using conventional fractionation schedules, pilocarpine at 5 mg three times per day is recommended.
• Patients must have evidence of preexisting salivary function and no medical contraindications to pilocarpine therapy.
• The ideal duration of treatment with pilocarpine is undefined. The decision to extend treatment beyond three months can be based only on clinical judgment and not on evidence.
• It is reasonable to use pilocarpine for patients with symptomatic xerostomia following hyperfractionated or accelerated fractionation radiotherapy.

None provided

The recommendations are supported by randomized controlled trials.

Original 1998 Guideline

Pilocarpine at 5 mg to 10 mg orally three times per day produced subjective responses to treatment including improvements in overall xerostomia symptoms (Risk Ratio of improvement [RR], 1.83; 95% confidence interval, 1.34 to 2.49; p = 0.00013), oral dryness (RR, 1.60; 95% confidence interval, 1.17 to 2.19; p = 0.0035), and the need for salivary substitutes (RR, 2.51; 95% confidence interval, 1.51 to 4.15; p = 0.00035).

March 2004 Update

The information above remains current.

1998 Guideline

Adverse events were dose-related. Adverse parasympathetic events were reported by participants in randomized controlled trials, the most frequent and troublesome being increased sweating which occurred in about one-quarter of patients taking 5 mg three times per day and about one-half of patients taking 10 mg. Eighteen percent of patients discontinued treatment because of adverse effects during a 36-month maintenance study. None of the events reported in any of these studies were classified as severe or life threatening.

March 2004 Update

The information above remains current.

Care has been taken in the preparation of the information contained in this document. Nonetheless, any person seeking to apply or consult these guidelines is expected to use independent medical judgment in the context of individual clinical circumstances or seek out the supervision of a qualified clinician. Cancer Care Ontario makes no representation or warranties of any kind whatsoever regarding their content or use or application and disclaims any responsibility for their application or use in any way.

An implementation strategy was not provided.

Living with Illness

Effectiveness

• Head and Neck Cancer Disease Site Group. Hodson DI, Haines T, Berry M. Symptomatic treatment of radiation-induced xerostomia in head and neck cancer patients [full report]. Toronto (ON): Cancer Care Ontario (CCO); 2004 Mar [online update]. 11 p. (Practice guideline report; no. 5-5). [29 references]

Not applicable: The guideline was not adapted from another source.

1998 Oct 15 (revised 2004 Mar)

Program in Evidence-based Care - State/Local Government Agency [Non-U.S.]

The Practice Guidelines Initiative (PGI) is the main project of the Program in Evidence-based Care (PEBC), a Province of Ontario initiative sponsored by Cancer Care Ontario and the Ontario Ministry of Health and Long-Term Care.

Cancer Care Ontario
Ontario Ministry of Health and Long-Term Care

Provincial Head and Neck Cancer Disease Site Group

Members of the Head and Neck Cancer Disease Site Group disclosed potential conflict of interest information.

None available

This summary was completed by ECRI on August 19, 1999. The information was verified by the guideline developer as of September 17, 1999. This NGC summary was updated by ECRI on December 17, 2001. The updated information was reviewed by the guideline developer as of January 10, 2002. This NGC summary was updated by ECRI on March 20, 2003. The information was verified by the guideline developer on May 8, 2003. This NGC summary was updated again on June 29, 2004. The information was verified by the guideline developer on July 19, 2004.