Abstract

Background: Patients with recurrent/metastatic uterine leiomyosarcoma (U-LMS) have a dismal prognosis. This phase II study aims to evaluate trabectedin efficacy and safety in advanced U-LMS. Methods: Eligible patients had received ≥ one line of chemotherapy. Gemcitabine ± docetaxel naive patients were randomised to Arm A: trabectedin 1.3 mg/m2 or calibration Arm B: gemcitabine 900 mg/m2 and docetaxel 75 mg/m2. Patients who had already received gemcitabine ± docetaxel directly entered Arm A. Primary end-point: 6-month progression-free rate (PFS-6). The null hypothesis that the true PFS-6 = 14% was tested against a one-sided alternative. This design yielded a 5% type I error rate and 90% power when the true PFS-6 is 25%. Results: Overall, 126 patients entered Arm A (45 from randomisation and 81 directly) and 42 Arm B. Arm A patients characteristics: median age = 57; ≥2 previous chemotherapy lines = 37.4%; metastatic disease = 93%. The study met the condition for trabectedin activity: PFS-6 = 35.2% (95% CI: 26.2–45). No difference in PFS by the number of previous chemotherapy lines emerged. Median OS = 20.6 months (IQR: 8–36.4). In Arm B, the PFS-6 = 51.5% (95% CI: 33.5–69.2). No toxic deaths occurred. In Arm A, only 4 patients interrupted treatment for toxicity. Conclusions: Trabectedin is active and well tolerated, retaining similar efficacy across one to three previous lines of chemotherapy. © 2018, Cancer Research UK.
Original languageEnglish
Pages (from-to)565-571
Number of pages7
JournalBritish Journal of Cancer
Volume119
Issue number5
DOIs
Publication statusPublished - 2018

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Keywords

  • alanine aminotransferase
  • anthracycline
  • aspartate aminotransferase
  • creatinine
  • dexamethasone
  • docetaxel
  • gemcitabine
  • hemoglobin
  • ifosfamide
  • trabectedin
  • abdominal hysterectomy
  • abdominal pain
  • adjuvant radiotherapy
  • adult
  • advanced cancer
  • aged
  • allergic reaction
  • anorexia
  • Article
  • atrial fibrillation
  • cancer combination chemotherapy
  • cancer diagnosis
  • cancer fatigue
  • cancer localization
  • cancer pain
  • cancer prognosis
  • cancer radiotherapy
  • cancer recurrence
  • cancer staging
  • cancer surgery
  • cholecystitis
  • colon obstruction
  • constipation
  • controlled study
  • dermatitis
  • diarrhea
  • drug efficacy
  • drug safety
  • dyspnea
  • enteritis
  • external beam radiotherapy
  • extravasation
  • female
  • fever
  • fistula
  • human
  • hydronephrosis
  • hyperglycemia
  • hyponatremia
  • infusion related reaction
  • intestine perforation
  • liver toxicity
  • lung embolism
  • lymph node dissection
  • major clinical study
  • metastasis
  • multicenter study
  • multimodality cancer therapy
  • multiple cycle treatment
  • nausea and vomiting
  • null hypothesis
  • patient history of chemotherapy
  • peripheral edema
  • phase 2 clinical trial
  • priority journal
  • progression free survival
  • randomized controlled trial
  • rectum perforation
  • salpingooophorectomy
  • sensory neuropathy
  • side effect
  • single blind procedure
  • treatment interruption
  • treatment planning
  • urogenital tract disease
  • uterus sarcoma
  • vein thrombosis

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