Pilocarpine Concurrent With Radiation Therapy Is Useful in Preserving Salivary Flow

SAN FRANCISCO—Definitive 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% were married.

Swallowing Dysfunction

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.