title: Phase I trial of concomitant chemoradiotherapy for cervical cancer and other advanced pelvic malignancies.
abstract: Purpose. The aim of this study was to determine the feasibility and toxicity of concomitant hydroxyurea (HU) and escalating doses of 5-fluorouracil (5-FU) in locally advanced cervical cancer and other pelvic malignancies undergoing radiation therapy (RT). Methods. Treatment consisted of 5-FU, HU, and pelvic RT delivered in an alternate-week fashion. 5-FU was administered as a continuous intravenous infusion at a starting dose of 600 mg/m2/day and was escalated to 1000 mg/m2/day in cohorts of three patients. The HU dose was 500 mg twice daily. Chemoradiotherapy was administered on a 5-day cycle. Following a 9-day rest, the cycle was repeated until the completion of the pelvic RT. Results. Twenty-one patients (18 cervix, 1 bladder, 1 vagina, 1 ovary) were enrolled. 5-FU escalation to 1000 mg/m2/day was well tolerated. No patients developed grade 3-4 hematologic toxicity. Grade 2 leukopenia was noted in 3 patients (14.3%). Grade 3 mucositis, diarrhea, and dermatitis occurred in 10, 10, and 5% of patients, respectively. None of the 99 treatment cycles were delayed secondary to acute toxicity. The overall response rate in the 18 cervical cancer patients was 89% (78% complete, 11% partial). Conclusions. Concomitant continuous infusion 5-FU, twice daily HU, and pelvic RT delivered in an alternate-week fashion is well tolerated. Further study is necessary to evaluate the therapeutic efficacy of this regimen in patients with advanced cervical and other pelvic malignancies.
authors.affiliation: Department of Radiation and Cellular Oncology, University of Chicago Hospitals,Chicago, Illinois, 60637, USA. mundt@rover.uchicago.Edu
authors.forename: A J
authors.initials: AJ
authors.lastname: Mundt
authors.forename: J
authors.initials: J
authors.lastname: Rotmensch
authors.forename: S
authors.initials: S
authors.lastname: Waggoner
authors.forename: C
authors.initials: C
authors.lastname: Quiet
authors.forename: G
authors.initials: G
authors.lastname: Fleming
mesh_terms: D000328:Adult; D000368:Aged; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage; D000970:Antineoplastic Agents / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D003131:Combined Modality Therapy; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D006801:Humans; D006918:Hydroxyurea / Q000008:administration & dosage; D008875:Middle Aged; D009367:Neoplasm Staging; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy*; D011878:Radiotherapy / Q000009:adverse effects; D013997:Time Factors; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy*; D002583:Uterine Cervical Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy*; D014625:Vaginal Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy*
chemical_list: D000964:Antimetabolites, Antineoplastic; D000970:Antineoplastic Agents; D005472:Fluorouracil; D006918:Hydroxyurea