The 14 reports in this special supplement discuss theuse of the cytoprotectant amifostine in patients withcancer of the head and neck, esophagus, lung, andcervix, as well as those with lymphoma and acutemyelogenous leukemia. Discussions focus on thepotential of this agent to both reduce radiation sideeffects such as xerostomia and permit doseescalation of chemotherapy and/or radiotherapy.Improvements in treatment outcome and quality oflife as a result of cytoprotection are examined.
HOUSTON-In head andneck cancer, intensity-modulatedradiotherapy (IMRT) may reducesome, but does not eliminate treatmenttoxicity, according to studiescomparing IMRT vs standard radiotherapyin this patient population.Investigators have found reducedrates of xerostomia but littledifference in acute grade 3 mucositis,reported David I.Rosenthal, MD, associate professorof radiation oncology atThe University of Texas M. D.Anderson Cancer Center.Dr. Rosenthal is therefore undertakinga phase II study to determinewhether cytoprotection withamifostine can reduce those sideeffects. "IMRT leaves 70% of patientswith at least some symptomsof dry mouth ," he said.He added that IMRT can reducexerostomia for many patients butis still associated with mucositis.Late grade 2 to 3 xerostomia wasreported as 84% with conventionalRT vs 30% with IMRT, but grade3 or 4 mucositis was more commonwith IMRT vs conventionalRT (42% vs 25%), and more IMRTpatients required G-tubes (25% vs18%); these differences are notstatistically significant.Dr. Rosenthal said that some ofthese effects might be explained bythe fact that while IMRT providesrelative sparing of the parotidgland, it does not reliably spare thesubmandibular gland.25 Gy Threshold
"There appears to be a steepsection of the dose-response curvefor xerostomia at about 25 Gy, thatsome have referred to as a threshold.Patients who get more dosehave little recovery of salivary glandfunction at 12 months," he noted."If the planned mean dose to theparotid gland is more than 24 to 26Gy, then IMRT may have little ifany benefit compared with conventionalradiotherapy, and thereis considerable increased cost."He explained that two-thirds ofstimulated salivary flow is fromthe parotid gland, and said the majorityof unstimulated salivary flowcomes from the submandibulargland. "The majority of xerostomiasymptoms are related to lackof basal unstimulated salivarygland flow that is primarily fromthe submandibular gland, and notrelated to the parotids," he said. Inthe normal setting, stimulated flowoccurs for less than 1 hour per day,during eating. Some studies suggestthat the submandibular glandmay contribute as much as 90% oftotal salivary output when patientsare not eating.Phase II Study
Dr. Rosenthal's phase II studyin head and neck cancer patientswill assess whether amifostine (500mg SC daily prior to radiation) canreduce IMRT-associated xerostomiaand mucositis and preservefunction of the submandibular andsublingual salivary glands.The treatment regimen includesdefinitive treatment with 66 Gy ofradiation in 30 fractions or postoperativetreatment with 60 Gy in30 fractions. The primary endpointis the preservation of submandibularand sublingual salivary flow,plus subjective xerostomia scores.Secondary endpoints include theparotid dose-volume histogram,mucositis in lower-dose RT areas,scalp hair-loss patterns, and dysphagiaas measured by the PerformanceStatus Score."Our hypothesis is thatcombined physical radiotherapydose-sparing by IMRT andamifostine cytoprotection willimprove global salivary sparingand decrease xerostomia," Dr.Rosenthal said.
Chao KS, Majhail N, Huang C, etal: Intensity-modulated radiation therapyreduces late salivary toxicity withoutcompromising tumor control inpatients with orapharyngeal carcinoma:A comparison with conventionaltechniques. Radiother Oncol 61:275-280, 2001.
Eisbruch A, Ten Kaen RK, KimHM, et al: Dose, volume and functionrelationships in parotid salivary glandsfollowing conformal and intensitymodulatedirradiation of head andneck cancer. Int J Radiation Oncol BioPhys 45:577-587, 1999.
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