Final results of a randomized phase III trial of induction chemotherapy followed by concurrent chemoradiotherapy versus concurrent chemoradiotherapy alone in patients with stage IVA and IVB nasopharyngeal carcinoma-Taiwan Cooperative Oncology Group (TCOG) 1303 Study

R L Hong, C F Hsiao, L L Ting, J Y Ko, C W Wang, J T C Chang, P J Lou, H M Wang, M H Tsai, S C Lai, T W Liu

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

Background: Concurrent chemoradiotherapy (CCRT) is superior to radiotherapy alone for treating locoregionally advanced nasopharyngeal carcinoma (NPC). Whether adding induction chemotherapy (IC) further improves the outcome warrants investigation.

Patients and methods: This open-label multicenter phase III trial was conducted at 11 institutions in Taiwan. Patients with stage IVA or IVB NPC were randomized to receive IC followed by CCRT (I-CCRT) or CCRT alone. Patients in the I-CCRT arm received 3 cycles of mitomycin C, epirubicin, cisplatin, and 5-fluorouracil/leucovorin (MEPFL). All patients received 30 mg/m2 cisplatin weekly during radiotherapy, which was delivered as 1.8-2.2 Gy per fraction with five daily fractions per week, to a total dose of 70 Gy or greater to the primary tumor and 66-70 Gy to the involved neck. The primary endpoint was disease-free survival (DFS).

Results: In this study, 240 and 239 patients were randomized to CCRT and I-CCRT arm, respectively. The most prominent toxicities of induction were leukopenia (grade 3 and 4: 47% and 12%) and thrombocytopenia (grade 3 and 4: 24% and 3%). During radiotherapy, severe mucositis was the major side effect in both arms; an increased number of patients in the I-CCRT arm had myelosuppression; hence, discontinuation of weekly cisplatin was more common. After a median follow-up of 72.0 months, the I-CCRT arm had significantly higher DFS than that of the CCRT arm (5-year rate 61% vs 50%; hazard ratio = 0·739, 95% confidence interval (CI)= 0·565-0·965; P = 0·0264), after stratified for N3b and LDH, and adjusted for T stage.

Conclusion: Induction with MEPFL before CCRT was tolerable and significantly improved the DFS of patients with stage IVA and IVB NPC though overall survival not improved.

Clinical trial information: NCT00201396.

Original languageEnglish
JournalAnnals of Oncology
DOIs
Publication statusE-pub ahead of print - Jul 17 2018
Externally publishedYes

Fingerprint

Induction Chemotherapy
Chemoradiotherapy
Taiwan
Arm
Cisplatin
Disease-Free Survival
Radiotherapy
Nasopharyngeal carcinoma
Epirubicin
Mucositis
Leucovorin
Leukopenia
Mitomycin
Fluorouracil
Neck
Clinical Trials
Confidence Intervals

Cite this

@article{d4c1045bc4bc4b3ab96f5e780ed55933,
title = "Final results of a randomized phase III trial of induction chemotherapy followed by concurrent chemoradiotherapy versus concurrent chemoradiotherapy alone in patients with stage IVA and IVB nasopharyngeal carcinoma-Taiwan Cooperative Oncology Group (TCOG) 1303 Study",
abstract = "Background: Concurrent chemoradiotherapy (CCRT) is superior to radiotherapy alone for treating locoregionally advanced nasopharyngeal carcinoma (NPC). Whether adding induction chemotherapy (IC) further improves the outcome warrants investigation.Patients and methods: This open-label multicenter phase III trial was conducted at 11 institutions in Taiwan. Patients with stage IVA or IVB NPC were randomized to receive IC followed by CCRT (I-CCRT) or CCRT alone. Patients in the I-CCRT arm received 3 cycles of mitomycin C, epirubicin, cisplatin, and 5-fluorouracil/leucovorin (MEPFL). All patients received 30 mg/m2 cisplatin weekly during radiotherapy, which was delivered as 1.8-2.2 Gy per fraction with five daily fractions per week, to a total dose of 70 Gy or greater to the primary tumor and 66-70 Gy to the involved neck. The primary endpoint was disease-free survival (DFS).Results: In this study, 240 and 239 patients were randomized to CCRT and I-CCRT arm, respectively. The most prominent toxicities of induction were leukopenia (grade 3 and 4: 47{\%} and 12{\%}) and thrombocytopenia (grade 3 and 4: 24{\%} and 3{\%}). During radiotherapy, severe mucositis was the major side effect in both arms; an increased number of patients in the I-CCRT arm had myelosuppression; hence, discontinuation of weekly cisplatin was more common. After a median follow-up of 72.0 months, the I-CCRT arm had significantly higher DFS than that of the CCRT arm (5-year rate 61{\%} vs 50{\%}; hazard ratio = 0·739, 95{\%} confidence interval (CI)= 0·565-0·965; P = 0·0264), after stratified for N3b and LDH, and adjusted for T stage.Conclusion: Induction with MEPFL before CCRT was tolerable and significantly improved the DFS of patients with stage IVA and IVB NPC though overall survival not improved.Clinical trial information: NCT00201396.",
author = "Hong, {R L} and Hsiao, {C F} and Ting, {L L} and Ko, {J Y} and Wang, {C W} and Chang, {J T C} and Lou, {P J} and Wang, {H M} and Tsai, {M H} and Lai, {S C} and Liu, {T W}",
year = "2018",
month = "7",
day = "17",
doi = "10.1093/annonc/mdy249",
language = "English",
journal = "Annals of Oncology",
issn = "0923-7534",
publisher = "Oxford University Press",

}

TY - JOUR

T1 - Final results of a randomized phase III trial of induction chemotherapy followed by concurrent chemoradiotherapy versus concurrent chemoradiotherapy alone in patients with stage IVA and IVB nasopharyngeal carcinoma-Taiwan Cooperative Oncology Group (TCOG) 1303 Study

AU - Hong, R L

AU - Hsiao, C F

AU - Ting, L L

AU - Ko, J Y

AU - Wang, C W

AU - Chang, J T C

AU - Lou, P J

AU - Wang, H M

AU - Tsai, M H

AU - Lai, S C

AU - Liu, T W

PY - 2018/7/17

Y1 - 2018/7/17

N2 - Background: Concurrent chemoradiotherapy (CCRT) is superior to radiotherapy alone for treating locoregionally advanced nasopharyngeal carcinoma (NPC). Whether adding induction chemotherapy (IC) further improves the outcome warrants investigation.Patients and methods: This open-label multicenter phase III trial was conducted at 11 institutions in Taiwan. Patients with stage IVA or IVB NPC were randomized to receive IC followed by CCRT (I-CCRT) or CCRT alone. Patients in the I-CCRT arm received 3 cycles of mitomycin C, epirubicin, cisplatin, and 5-fluorouracil/leucovorin (MEPFL). All patients received 30 mg/m2 cisplatin weekly during radiotherapy, which was delivered as 1.8-2.2 Gy per fraction with five daily fractions per week, to a total dose of 70 Gy or greater to the primary tumor and 66-70 Gy to the involved neck. The primary endpoint was disease-free survival (DFS).Results: In this study, 240 and 239 patients were randomized to CCRT and I-CCRT arm, respectively. The most prominent toxicities of induction were leukopenia (grade 3 and 4: 47% and 12%) and thrombocytopenia (grade 3 and 4: 24% and 3%). During radiotherapy, severe mucositis was the major side effect in both arms; an increased number of patients in the I-CCRT arm had myelosuppression; hence, discontinuation of weekly cisplatin was more common. After a median follow-up of 72.0 months, the I-CCRT arm had significantly higher DFS than that of the CCRT arm (5-year rate 61% vs 50%; hazard ratio = 0·739, 95% confidence interval (CI)= 0·565-0·965; P = 0·0264), after stratified for N3b and LDH, and adjusted for T stage.Conclusion: Induction with MEPFL before CCRT was tolerable and significantly improved the DFS of patients with stage IVA and IVB NPC though overall survival not improved.Clinical trial information: NCT00201396.

AB - Background: Concurrent chemoradiotherapy (CCRT) is superior to radiotherapy alone for treating locoregionally advanced nasopharyngeal carcinoma (NPC). Whether adding induction chemotherapy (IC) further improves the outcome warrants investigation.Patients and methods: This open-label multicenter phase III trial was conducted at 11 institutions in Taiwan. Patients with stage IVA or IVB NPC were randomized to receive IC followed by CCRT (I-CCRT) or CCRT alone. Patients in the I-CCRT arm received 3 cycles of mitomycin C, epirubicin, cisplatin, and 5-fluorouracil/leucovorin (MEPFL). All patients received 30 mg/m2 cisplatin weekly during radiotherapy, which was delivered as 1.8-2.2 Gy per fraction with five daily fractions per week, to a total dose of 70 Gy or greater to the primary tumor and 66-70 Gy to the involved neck. The primary endpoint was disease-free survival (DFS).Results: In this study, 240 and 239 patients were randomized to CCRT and I-CCRT arm, respectively. The most prominent toxicities of induction were leukopenia (grade 3 and 4: 47% and 12%) and thrombocytopenia (grade 3 and 4: 24% and 3%). During radiotherapy, severe mucositis was the major side effect in both arms; an increased number of patients in the I-CCRT arm had myelosuppression; hence, discontinuation of weekly cisplatin was more common. After a median follow-up of 72.0 months, the I-CCRT arm had significantly higher DFS than that of the CCRT arm (5-year rate 61% vs 50%; hazard ratio = 0·739, 95% confidence interval (CI)= 0·565-0·965; P = 0·0264), after stratified for N3b and LDH, and adjusted for T stage.Conclusion: Induction with MEPFL before CCRT was tolerable and significantly improved the DFS of patients with stage IVA and IVB NPC though overall survival not improved.Clinical trial information: NCT00201396.

U2 - 10.1093/annonc/mdy249

DO - 10.1093/annonc/mdy249

M3 - Article

C2 - 30016391

JO - Annals of Oncology

JF - Annals of Oncology

SN - 0923-7534

ER -