Efficacy of combination chemotherapy using irinotecan and nedaplatin for patients with recurrent and refractory endometrial carcinomas: preliminary analysis and literature review

Cancer Chemother Pharmacol. 2018 Jan;81(1):111-117. doi: 10.1007/s00280-017-3454-y. Epub 2017 Nov 9.

Abstract

Purpose: We aimed to retrospectively evaluate the efficacy and toxicity of an irinotecan hydrochloride (CPT) and nedaplatin (N) combination therapy for recurrent and refractory endometrial carcinoma, administered based on UGT1A1 genotype.

Methods: Between 2009 and 2017, 21 patients who received CPT-N therapy for recurrent endometrial carcinoma as second- or third-line chemotherapy at our hospital were identified. The CPT-N regimen included 40-70 mg/m2 of CPT-11 on days 1, 8, and 15, and 50 mg/m2 of nedaplatin on day 1, q4 weeks.

Results: The median patient age was 63 years. The number of prior chemotherapeutic regimens ranged from 1 to 2. Two patients had prior pelvic irradiation. The response rate [ratio of complete remission (CR) to partial remission (PR)] of CPT-N therapy was 3 of 21 (14.3%), and clinical benefit rate (CBR) [the combined percentages of CR, PR, and stable disease (SD)] was 9 of 21 (42.8%). Toxicities included grade 3 neutropenia [4 (19.0%) cases], grade 3 febrile neutropenia [2 (9.5%) cases], and grade 3 diarrhea [3 (14.3%) cases]; all resolved with conservative treatment. Patients with a wild-type UGT1A1 status received higher doses of CPT-11 (p = 0.048) and had similar RR and CBR compared to those with a UGT1A1*6 and *28 status. There were no significant differences in frequencies of hematological or non-hematological toxicities, regardless of UGT1A1 status.

Conclusions: The CPT-N regimen for recurrent and refractory endometrial carcinoma had tolerable side effects and significant efficacy. This regimen is a viable treatment option for endometrial carcinoma.

Keywords: Endometrial carcinoma; Irinotecan hydrochloride; Platinum; Recurrence; Second-line chemotherapy.

Publication types

  • Review

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Combined Chemotherapy Protocols / administration & dosage
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Dose-Response Relationship, Drug
  • Endometrial Neoplasms / drug therapy*
  • Endometrial Neoplasms / genetics
  • Female
  • Genotype
  • Glucuronosyltransferase / genetics*
  • Humans
  • Irinotecan / administration & dosage*
  • Irinotecan / adverse effects
  • Middle Aged
  • Neoplasm Recurrence, Local / drug therapy*
  • Organoplatinum Compounds / administration & dosage*
  • Organoplatinum Compounds / adverse effects
  • Remission Induction
  • Retrospective Studies

Substances

  • Organoplatinum Compounds
  • Irinotecan
  • nedaplatin
  • UGT1A1 enzyme
  • Glucuronosyltransferase