title: A pilot trial of TAC (paclitaxel, doxorubicin, and carboplatin) chemotherapy with filgastrim (r-metHuG-CSF) support followed by radiotherapy in patients with "high-risk" endometrial cancer.
abstract: OBJECTIVE
  To determine the toxicity, tolerability, and feasibility of delivering combination chemotherapy with subsequent radiation therapy to women with high-risk endometrial cancer and to evaluate the long-term bowel toxicity of this regimen.
  
  
  METHODS
  The trial was approved by the Dana Farber/Partners Cancer Care (DFPCC) Institutional Review Board (IRB). Patients with stage 3 or stage 4 endometrial cancer or patients with high-risk histology and any stage disease were prospectively entered. Complete surgical staging and a normal gated blood pool scan were required prior to entry. Patients were treated with three cycles of paclitaxel (160 mg/m(2) ), doxorubicin (45 mg/m(2)) and carboplatin (AUC 5) (TAC) all on day 1 of a 21-day schedule as an outpatient with G-CSF support. At the conclusion of chemotherapy, patients received radiation therapy (4500 cGy to the whole pelvis) commencing within 35 days of the last cycle of chemotherapy. Paraaortic radiation and/or vaginal brachytherapy were allowed at the discretion of the treating radiation oncologist.
  
  
  RESULTS
  Twenty patients were entered onto the trial from November 2000 through February 2003. Eighteen patients successfully completed the trial, and two patients came off trial during chemotherapy (both later completed planned radiation therapy). Patients were initially stage 1 (n = 3), stage 3 (n = 14), and stage 4 (n = 3). Papillary serous was the dominant histology with 13 patients. Chemotherapy was given on average within 32 days of surgery (range 11-63 days) and radiation was initiated on average within 14 weeks of surgery (range 10-18 weeks). Chemotherapy was well tolerated, with 57 total cycles delivered of a planned 60 cycles. Two patients required dose modification in two cycles (two patients in cycle 3 secondary to hematologic toxicity). No grade 3 or grade 4 neurotoxicity was reported. There were six episodes of grade 3 short-term toxicity with radiation therapy reported in a single patient. Late radiotherapy toxicity included bowel obstruction requiring laparotomy in two patients and grade 3 constipation in one patient. Late radiation toxicity data are still being collected as follow-up continues.
  
  
  CONCLUSIONS
  The TAC chemotherapy regimen is well tolerated and three cycles were delivered successfully with G-CSF support without evidence of the neurotoxicity or cardiac toxicity reported with the cisplatin containing TAP regimen. Standard radiation was deliverable following TAC therapy without excessive toxicity. Further study of this regimen with subsequent radiation therapy is warranted in patients at risk for systemic and regional recurrence of their malignancy.
authors.affiliation: Division of Gynecologic Oncology, Massachusetts General Hospital, Boston, MA 02114, USA. lduska@partners.org
authors.forename: Linda R
authors.initials: LR
authors.lastname: Duska
authors.forename: Ross
authors.initials: R
authors.lastname: Berkowitz
authors.forename: Ursula
authors.initials: U
authors.lastname: Matulonis
authors.forename: Michael
authors.initials: M
authors.lastname: Muto
authors.forename: Annekathryn
authors.initials: A
authors.lastname: Goodman
authors.forename: James F
authors.initials: JF
authors.lastname: McIntyre
authors.forename: Amber
authors.initials: A
authors.lastname: Klein
authors.forename: Tina
authors.initials: T
authors.lastname: Atkinson
authors.forename: Michael V
authors.initials: MV
authors.lastname: Seiden
authors.forename: Susana
authors.initials: S
authors.lastname: Campos
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D001918:Brachytherapy; D016190:Carboplatin / Q000008:administration & dosage / Q000009:adverse effects; D003131:Combined Modality Therapy; D004317:Doxorubicin / Q000008:administration & dosage / Q000009:adverse effects; D004334:Drug Administration Schedule; D016889:Endometrial Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy* / Q000601:surgery; D005260:Female; D000069585:Filgrastim; D016179:Granulocyte Colony-Stimulating Factor / Q000008:administration & dosage; D006801:Humans; D008875:Middle Aged; D009367:Neoplasm Staging; D017239:Paclitaxel / Q000008:administration & dosage / Q000009:adverse effects; D010865:Pilot Projects; D011994:Recombinant Proteins; D012307:Risk Factors
chemical_list: D011994:Recombinant Proteins; D016179:Granulocyte Colony-Stimulating Factor; D004317:Doxorubicin; D016190:Carboplatin; D017239:Paclitaxel; D000069585:Filgrastim