A Phase 1/2 Study of Carbon Ion Radiation Therapy With Concurrent Chemotherapy for Locally Advanced Uterine Cervical Squamous Cell Carcinoma (Protocol 1302)

Int J Radiat Oncol Biol Phys. 2019 Jul 1;104(3):631-639. doi: 10.1016/j.ijrobp.2019.02.042. Epub 2019 Feb 27.

Abstract

Purpose: This study evaluated the safety and efficacy of carbon-ion radiation therapy (C-ion RT) with concurrent chemotherapy for locally advanced uterine cervical squamous cell carcinoma in a phase 1/2 clinical trial.

Methods and materials: Twenty-two patients were treated with C-ion RT with concurrent weekly cisplatin at a dose of 40 mg/m2. The phase 1 component evaluated the safety of 72.0 Gy (relative biological effectiveness) of C-ion RT with concurrent chemotherapy. In the phase 2 component, the safety and efficacy of C-ion RT with concurrent chemotherapy were assessed using the dose determined in phase 1.

Results: The median follow-up period was 32 months, and the median tumor size was 71 mm (range, 51-150 mm). No patient had dose-limiting toxicities in the phase 1 component; the recommended dose was determined to be 72.0 Gy (relative biological effectiveness) with 40 mg/m2 of cisplatin. In the phase 2 component, 2 patients developed grade 3 gastrointestinal tract toxicities. In patients treated with the recommended dose, the 2-year local control (LC), LC including salvage therapy, and overall survival rates were 67%, 81%, and 82%, respectively. The 2-year LC and overall survival rates for patients with tumor sizes ≤7.1 cm were 92% and 100%, respectively; for those with tumor sizes >7.1 cm they were 33% and 60%, respectively.

Conclusions: C-ion RT with concurrent weekly cisplatin was tolerated by patients with locally advanced uterine cervical squamous cell carcinoma. Outcomes were good in patients with tumor sizes ≤7.1 cm but not in those with larger tumors. The results of the present study should be validated with larger multi-institutional prospective studies. Further study is needed, and perhaps incorporating carbon ion external beam radiation with brachytherapy will further reduce the risk of central recurrence.

Publication types

  • Clinical Trial, Phase I
  • Clinical Trial, Phase II
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Agents / administration & dosage
  • Antineoplastic Agents / adverse effects*
  • Carcinoma, Squamous Cell / mortality
  • Carcinoma, Squamous Cell / pathology
  • Carcinoma, Squamous Cell / therapy*
  • Chemoradiotherapy / adverse effects*
  • Chemoradiotherapy / methods
  • Cisplatin / administration & dosage
  • Cisplatin / adverse effects*
  • Drug Administration Schedule
  • Female
  • Follow-Up Studies
  • Heavy Ion Radiotherapy / adverse effects*
  • Heavy Ion Radiotherapy / methods
  • Humans
  • Middle Aged
  • Radiotherapy Dosage
  • Relative Biological Effectiveness
  • Salvage Therapy
  • Survival Rate
  • Tumor Burden
  • Uterine Cervical Neoplasms / mortality
  • Uterine Cervical Neoplasms / pathology
  • Uterine Cervical Neoplasms / therapy*

Substances

  • Antineoplastic Agents
  • Cisplatin