Preliminary Evidence of Benefit From Amifostine for Cytoprotection in Patients With Cervical Cancer

CHICAGO-"There is aneed for toxicity reduction in cervicalcancer patients and some preliminaryevidence that amifostinemay be beneficial," notes WilliamSmall, Jr., MD, associate professorof clinical radiology, division ofradiation oncology at NorthwesternUniversity Medical School. Hediscussed Radiation Therapy OncologyGroup (RTOG) plans to addan amifostine (Ethyol) arm to theongoing RTOG C-0116 study ofextended-field external irradiated(EFER) and intracavitary radiotherapyand chemotherapy in cervicalcancer patients with positivepara-aortic or high common iliaclymph nodes.Dr. Small said that while theincidence of cervical cancer in theUS has dropped from 12,200 in2000 to a predicted 10,520 in 2004,"treatment-associated severe andfatal toxicities are much higher thanmost of us realize."Chemoradiotherapy is now thede facto standard of care but isassociated with high rates of acutegrade 3 or 4 toxicities. In the RTOG90-01 study, for example, patientshad significant nausea/vomiting(14% grade 3 and 3% grade 4),bowel and rectal problems (12%grade 3 and 5% grade 4), and hematologictoxicity (57% grade 3and 16% grade 4). In the GOG(Gynecologic Oncology Group)-120 trial of pelvic RT combinedwith cisplatin (Platinol) vs cisplatin/fluorouracil/hydroxyurea vshydroxyurea, both cisplatin armsimproved survival. Yet, this benefitcame at the cost of leukopenia(21% grade 3 and 2% grade 4) andgastrointestinal (10% grade 3 and5% grade 4) and genitourinary toxicity(3% grade 3 and 2% grade 4).Cervical cancer patients whohave metastases to the para-aorticlymph nodes can be cured withextended-field RT despite secondechelonlymph node metastases-but at the expense of high RT toxicity,Dr. Small said. "Given thepositive results of combined therapyin pelvic-only disease, combinationextended-field RT and chemotherapyin para-aortic nodepositive patients appears to be indicated,"he noted.Extended-field RT alone producedlocal control of about 55%and 5-year survival of about 30%in these patients, but nearly one infour patients had some type ofgrade 4 toxicity.RTOG C-0116
"RTOG C-0116 is a prospectiveclinical trial designed to test thehypothesis that amifostine can reduceradiotherapy and chemotherapytoxicity in treatment of cervicalcancer. Eligibility includes patientswith para-aortic metastases,as this patient population is believedto be at highest risk for treatmentmortality," Dr. Small said.The trial has two phases, thefirst being treatment with extended-field RT, brachytherapy, andconcurrent cisplatin without amifostine.This arm was designed toobtain a good estimate of the truetoxicity of extended-field RT andconcurrent cisplatin because theinvestigators believed there was noadequate historical control.That phase has been completed(with 26 patients), and grade 3 or 4toxicity was 77% (excluding grade3 leukopenia). This toxicity levelwas higher than anticipated in thestudy protocol, according to whichthe study would continue to phaseII, with addition of amifostine, ifthe grade 3/4 toxicity was 30% to62.5%."In our experience withoutamifostine, we were uncommonlyable to give patients the full plannedsix doses of chemotherapy," Dr.Small said. Per protocol, the investigatorsare seeking a study amendmentto permit continuation ofthe study. They hope to treat 18 to20 patients in the second phase ofthe study, with amifostine cytoprotectionadded, and to reportefficacy data by next year.