A Phase I Study using low-dose fractionated whole abdominal radiotherapy as a chemopotentiator to full-dose cisplatin for optimally debulked stage III/IV carcinoma of the endometrium

Gynecol Oncol. 2011 Jul;122(1):59-62. doi: 10.1016/j.ygyno.2011.03.007. Epub 2011 Apr 6.

Abstract

Objective: To evaluate the feasibility of combining low-dose fractionated whole abdominal radiation (LDF-WAR) with weekly full-dose cisplatin (FD-CDDP) for patients with stage III/IV endometrial carcinoma.

Methods: Patients with optimally debulked stage III/IV carcinoma of the endometrium (without extra-abdominal disease) were eligible for the study. Postoperatively, patients received the institutional standard systemic chemotherapy and vaginal brachytherapy. Patients then underwent experimental six weekly cycles of FD-CDDP (40 mg/m², maximum 70 mg IV) followed by LDF-WAR 6-8 hours after initiation of chemotherapy. In a conservative design, 6 patients were accrued to two sequential cohorts of LDF-WAR, at 0.5 Gy/fraction [Fx] (total 3 Gy) and 0.75 Gy/Fx (total 4.5 Gy). Toxicities and laboratory studies were evaluated at each visit.

Results: Twelve patients were enrolled from January 2005 to June 2009 with median follow-up of 13.5 months (range: 5-27 months). Seventy-five percent of enrolled patients had uterine papillary serous histology. Eleven patients at least partially completed therapy (range: 2-6 cycles of FD-CDDP/LDF-WAR) with one additional patient opting out at the higher dose level. Combination therapy overall was well tolerated. Three patients in each cohort experienced grade 3 acute hematologic events with one recorded grade 4 toxicity in the second cohort. Of patients receiving any of the experimental treatment, five have experienced recurrences. Three of these patients were in cohort one and received 0.5 Gy/Fx LDF-WAR.

Conclusion: Combination therapy with LDF-WAR as a novel chemopotentiator to FD-CDDP is a feasible adjuvant regimen in optimally debulked patients with stage III/IV endometrial carcinoma. Further investigation is warranted to determine treatment efficacy.

Publication types

  • Clinical Trial, Phase I

MeSH terms

  • Aged
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Brachytherapy
  • Carboplatin / administration & dosage
  • Chemotherapy, Adjuvant
  • Cisplatin / therapeutic use*
  • Dose Fractionation, Radiation
  • Endometrial Neoplasms / drug therapy*
  • Endometrial Neoplasms / pathology
  • Endometrial Neoplasms / radiotherapy*
  • Endometrial Neoplasms / surgery
  • Female
  • Humans
  • Hysterectomy
  • Lymph Node Excision
  • Middle Aged
  • Neoplasm Staging
  • Ovariectomy
  • Paclitaxel / administration & dosage

Substances

  • Carboplatin
  • Paclitaxel
  • Cisplatin