SAN FRANCISCODefinitive head and neck radiation produces two
treatment morbidities that can affect tolerance and result in treatment breaks.
Chronic xerostomia commonly occurs after 50 Gy of radiation and acute,
transient mucositis can cause treatment delays that affect the efficacy of the
regimen. The Radiation Therapy Oncology Group (RTOG) recently completed a
randomized, placebo-controlled trial to see if pilocarpine given concurrently
with radiation could prevent those toxicities.
Charles B. Scott, PhD, RTOG statistician based in Philadelphia,
reported that pilocarpine was significantly better than placebo at preserving
salivary flow but had no effect on mucositis or on quality of life in head and
neck cancer patients treated with radiation. Dr. Scott presented the trial on
behalf of lead authors Charles W. Scarantino, MD, of the Rex Cancer Center in
Raleigh and Francis G. LeVeque, DDS of Wayne State University in Detroit.
Preserving Salivary Flow
Pilocarpine has been approved for the treatment of
radiation-induced xerostomia. Dr. Scott said that the objective of this phase
III randomized study was to determine whether pilocarpine should be given
up-front, concurrently with radiation therapy for maximum efficacy in
preserving salivary flow.
"We used both a spit test as the objective measure and a
quality of life scale as a subjective measure," Dr. Scott said. The
researchers also examined the association between xerostomia and mucositis and
specifically asked whether pilocarpine affected radiation-induced mucositis.
Patients were scheduled to receive at least 50 Gy, affecting
50% of the volume of the major salivary glands. Unstimulated and stimulated
salivary samples were obtained prior to therapy and at 3 and 6 months following
radiation therapy. Patients could be either postoperative or inoperative.
Pilocarpine was given at 5 mg qid for 3 months. This was a randomized,
placebo-controlled trial, blinded to both the patient and the physician.
Of the 249 patients randomized between March 1998 and February
2000, 246 were available for analysis. Three patients were retrospectively made
ineligible. The average age was 60; 75% of the population were male; and 50%
In pretreatment evaluation, 95% of patients felt that they had
a normal amount of salivary flow prior to radiation therapy. In addition, 40%
complained of abnormal chewing or swallowing dysfunction and 50% felt that they
had disfigurement prior to radiation therapy.
"Pilocarpine was associated with a 37.5% better
unstimulated salivary flow compared to placebo at 3 months (P = 0.047).
Although patients could cross over at 3 months, at 6 months those randomized to
pilocarpine still had a 32% better unstimulated salivary flow (P =
0.09)," Dr. Scott said.
After 3 months of treatment, using the head and neck symptom
scale for quality of life, 75% of the patients on pilocarpine vs 66% on placebo
did not complain of pain. Swallowing dysfunction occurred in 77% of the
pilocarpine patients vs 82% in the placebo arm.
Mucositis was unaffected by pilocarpine treatment.
"Pilocarpine given concurrently with radiation affords an improvement in
salivary flow versus placebo but did not appear to affect the grade of
mucositis or to correlate with quality of life," Dr. Scott concluded.