Clinical outcomes of carbon ion radiotherapy with concurrent chemotherapy for locally advanced uterine cervical adenocarcinoma in a phase 1/2 clinical trial (Protocol 1001).

Noriyuki Okonogi,Kumiko Karasawa,Takashi Nakano,Shingo Kato,Daijiro Kobayashi,Tadashi Kamada,Masaru Wakatsuki,Shintaro Shiba,Hiroki Kiyohara,Makio Shozu

doi:10.1002/cam4.1305

Abstract

We conducted a phase 1/2 study to evaluate the efficacy and safety of carbon ion radiotherapy (C‐ion RT) with concurrent chemotherapy for locally advanced uterine cervical adenocarcinoma. Thirty‐three patients were enrolled between April 2010 and March 2014. Treatment consisted of C‐ion RT with concurrent weekly cisplatin at a dose of 40 mg/m2. In the phase 1 component, the total dose was escalated from 68.0 Gy (relative biological effectiveness [RBE]) to 74.4 Gy (RBE) to determine the maximum tolerated dose of C‐ion RT. In the phase 2 component, the efficacy and safety of C‐ion RT with concurrent chemotherapy were evaluated using the dose determined in the phase 1 component. The median follow‐up duration was 30 months. Two patients did not receive chemotherapy because of anemia or leukocytopenia immediately prior to commencing treatment; 31 patients were analyzed. None of the patients developed dose‐limiting toxicities. The recommended dose (RD) was determined to be 74.4 Gy (RBE). In the phase 2 component, two patients developed Grade 3–4 toxicities in the gastrointestinal tract, due to repeated laser coagulation or peritonitis caused by appendicitis. In the patients treated with the RD, the 2‐year local control, progression‐free survival, and overall survival rates were 71%, 56%, and 88%, respectively. C‐ion RT with concurrent weekly cisplatin was well tolerated in patients with locally advanced uterine cervical adenocarcinoma. Our findings support further investigations into the efficacy of this strategy.

Highlights

Uterine cervical cancer remains one of the most common cancers in women worldwide [1]
Recent studies have shown that Concurrent chemoradiotherapy (CCRT) and image-guided brachytherapy improve the clinical outcome of patients with cervical carcinoma, especially squamous cell carcinoma [9–11]
Of the 33 patients enrolled in this study, 27 had cervical adenocarcinoma and 6 had cervical adenosquamous carcinoma

Summary

Introduction

Uterine cervical cancer remains one of the most common cancers in women worldwide [1]. Recent studies have shown that CCRT and image-guided brachytherapy improve the clinical outcome of patients with cervical carcinoma, especially squamous cell carcinoma [9–11]. Uterine cervical adenocarcinomas are more radioresistant than squamous cell carcinomas [12, 14], with poorer local control (LC) and overall survival (OS). In a previous clinical trial [18], we investigated the treatment outcomes of C-ion RT for locally advanced uterine cervical adenocarcinomas. To improve LC and reduce the rate of DM, concurrent chemotherapy with C-ion RT (chemo-C-ion RT) was considered for locally advanced uterine cervical adenocarcinoma. We conducted a phase 1/2 clinical trial (protocol 1001) between April 2010 and March 2014 to evaluate the efficacy and safety of chemo- C-ion RT for locally advanced uterine cervical adenocarcinoma. The radiation dose was calculated for the target volume and surrounding normal structures and was expressed in Gy (relative biological effectiveness [RBE]), which was defined as the physical doses multiplied by the RBE of the C-ions [16, 24]

Materials and Methods

Study design

Results

Discussion