Abstract book - ESTRO meets Asia

S8 ESTRO meets Asia 2018

OC-022 a phase II study about locally advanced NPC treated with CCRT followed with metronomic chemotherapy M. Feng 1 , J. Lang 1 , Y. Gao 1 , B. Fu 1 , L. Li 1 , Y. huang 1 , P. xu 1 , Y. qi 1 , K. xu 1 , J. yin 1 , S. wang 1 , M. lan 1 , S. lu 1 1 Sichuan Cancer Hospital, radiation oncology, Chengdu, China Purpose or Objective The concurrent chemoradiotherapy is the standard treatment modality for NPC, however the adjuvant chemotherapy is still controversial because of no good response and substantial serious toxicities. Metronomic chemotherapy is a new dosing modality of chemotherapy which is in low-dosages with high frequency and continuous administration that has been rising in recent years. It could sustainably inhibit the proliferation of tumor endothelial cell, affect tumor stem cells and regulate the body's immune system. We aimed to evaluate the possible efficacy and toxicity in locally advanced NPC treated with concurrent chemoradiotherapy followed with the capecitabine metronomic chemotherapy. Material and Methods 67 III-IV stage (UICC 8th staging system) locally advanced NPC were included. All the patients received definitive CCRT followed with the capecitabine metronomic chemotherapy. For the control group, 75 patients received definitive CCRT with IMRT. The prescription dose was delivered as follows: GTV 68-74Gy, GTV-n 60-70Gy, HR- CTV 60-66Gy, LR-CTV 54-60Gy in 30-33 fractions. 2-3 cycles cisplatin-based chemotherapy was used. 3 cycles capecitabine (750mg/m 2 , bid) was used after the completion of CCRT. The Kaplan-Meier method was used to calculate LC, DMFS, PFS and OS. The acute and late toxicities were graded according to the CTCAE 3.0 scoring criteria. Results The median follow-up time was 24 months. The baseline had no significance between two groups. The 2-year OS and LC were similar (100%, 98.2%; 98.6%, 97.2% respectively). Compared with the control group, the 2- year DMFS and PFS were improved in the observation group (96.3%, 94.6%; 89.0%, 86.5%). There was no statistical difference about the OS, LC, DMFS and PFS ( P >0.05). For the acute toxicities, the incidence of G1-2 and G3-4 neutropenia in observational and control group were 50.7%, 58.6% and 14.9%, 20%, the incidence of G1-2 and G3-4 thrombocytopenia were 22.4%, 25.3% and 6%,9.3%, and the incidence of G1-2 and G3-4 vomit and nausea were 16.8%, 8% and 0%, 0% respectively. For the late toxicities, the incidence of G1-2 and G3-4 xerostomia were 56.7% 54.7% and 3%, 1.3% in the observational and control group respectively; the incidence of G1-2 and G3-4 hearing impairment were 47.8%, 38.7% and 0%, 1.3%; the incidence of G1-2 and G3-4 neck fibrosis were 16.4%, 21.3% and 0%, 0%. In addition, for the specific toxicity of capecitabine, all the toxicities were G1-2. And the incidence of limb numbness, rash, neuropathic headache and anaphylaxis were 32.8%, 28.3%, 17.9% and 3.0%. There was no significant difference about the toxicities between the two groups ( P >0.05). Conclusion the concurrent chemoradiotherapy followed with the capecitabine metronomic chemotherapy was a promising modality for locally advanced NPC patients. The 2-year DMFS and PFS was improved compared with the concurrent chemoradiotherapy, and the acute and late toxicity were all tolerable. The more and long follow-up studies should be carried out in the future.

66-70.4Gy to the gross tumor volumes (GTV), 57-60.8Gy to the high-risk clinical target volume (CTV1), 54-56Gy to the low-risk clinical target volume (CTV2), given in 30-32 fractions ， five times per week. Concurrently, S-1 was administrated twice per day orally based on the body surface area of patients (BSA<1.25m 2 , 40mg/m 2 ; BSA: 1.25-1.5m 2 , 40-60mg/m 2 ; BSA>1.5m 2 , 60mg/m 2 ) during the whole radiation course. The primary endpoints of this study were adverse events and progression-free survival. Results From May 12, 2013 to December 15, 2017, 131 patients with locally advanced NPC were enrolled in this study. Thirty-three patients (25.2%) were aged over 65 years. The distribution of disease was stage II in 21 (16.0%), stage III in 42 (32.0%), and stage IV in 68 (52.0%). Sixty-three (48.0%) patients had complete response (CR), and 65 (49.6%) had partial response (PR). The median follow-up time was 25.4 months (range 7 to 55). The 2-year progression-free survival (PFS), overall survival (OS), local recurrence-free survival (LRFS) and distant metastasis- free survival (DMFS) rates were 89.5%, 96.2%, 94.9% and 89.9%, respectively. The severity of most toxicities was mild. There was no grade 4 toxicity or treatment-related death. 103 patients (78.6%) had grade 1 or 2 mucositis. About two thirds had no hematological toxicity. Grade 1 hematological toxicities included leukopenia (22.1%), anemia (35.1%), and thrombocytopenia (24.4%). Grade 3 hematological toxicities were rarely seen.

Conclusion The results demonstrated that IMRT combined with concurrent S-1 chemotherapy was effective with mild toxicity for patients with locally advanced NPC.