| Literature DB >> 34706159 |
Jason Chia-Hsun Hsieh1,2,3, Pin-Chun Chiang1,3, Tsung-Min Hung3,4, Yin-Kai Chao3,5, Yung-Chia Kuo1,2,3, Chih-Tsung Wen3,5,6, Po-Jung Su2,3, Meng-Ting Peng2,3, Huan-Wu Chen3,7,8, Hui-Ling Liu9, Hsien-Kun Chang1,2,3, Min-Hsien Wu1,2,3, Hung-Ming Wang1,2,3.
Abstract
BACKGROUND: The optimal definitive chemotherapy regimen during concurrent chemoradiotherapy (CRT) for patients with advanced esophageal squamous cell carcinoma (ESCC) remains unclear because of conflicting evidence. This study aimed to compare the effectiveness of taxane-based chemotherapy with that of conventional cisplatin plus 5-fluorouracil (PF) as the chemotherapy regimen in definitive CRT for ESCC. PATIENTS AND METHODS: This retrospective study included patients with ESCC who received paclitaxel plus carboplatin (PC) or PF during definitive CRT between May 2012 and February 2015 in a medical center in Taiwan. Survival outcomes were compared after adjustment for risk factors.Entities:
Keywords: 5-fluorouracil; carboplatin; cisplatin; definitive chemoradiotherapy; esophageal squamous cell carcinoma; paclitaxel
Mesh:
Substances:
Year: 2021 PMID: 34706159 PMCID: PMC8633257 DOI: 10.1002/cam4.4025
Source DB: PubMed Journal: Cancer Med ISSN: 2045-7634 Impact factor: 4.452
FIGURE 1CONSORT flow diagram of patient enrollment
Clinicopathological patient characteristics by the group
| Parameters |
PC group (
|
PF group (
|
|
|---|---|---|---|
| Age (years), median (range) | 62(42–92) | 59 (39–89) | 0.065 |
| Sex | 0.436 | ||
| Male/female | 5 (6.0%)/78 (94.0%) | 13 (8.9%)/133 (91.1%) | |
| Histology | |||
| SqCC | 80 (96.4%) | 144 (98.6%) | |
| Adenocarcinoma | 2 (2.4%) | 1 (0.7%) | |
| Others | 1 (1.2%) | 1 (0.7%) | 0.314 |
| Stage (AJCC 8th edition) | |||
| IIA‐IIB | 2 (2.4%) | 8 (5.5%) | |
| IIIA | 5 (6.0%) | 4 (2.7%) | |
| IIIB | 42 (50.6%) | 62 (42.5%) | |
| IVA | 34 (40.9%) | 72 (49.3%) | 0.467 |
| Tumor location | |||
| Cervical | 7 (8.4%) | 15 (10.3%) | |
| Upper third | 15 (18.1%) | 31 (21.2%) | |
| Middle third | 31 (37.3%) | 51 (34.9%) | |
| Lower third | 29 (34.9%) | 48 (32.9%) | 0.896 |
| Performance status (ECOG) | |||
| 0–1 | 80 (96.4%) | 134 (91.8%) | |
| ≥2 | 3 (3.6%) | 12 (8.2%) | 0.185 |
| Cumulative radiation dose | |||
| <41.4 Gy | 8 (9.6%) | 20 (13.7%) | |
| ≥41.4 Gy | 75 (90.4%) | 126 (86.3%) | 0.367 |
| Surgery after CCRT | |||
| No | 53 (63.9%) | 92 (63.0%) | |
| Yes | 30 (36.1%) | 54 (37.0%) | 0.899 |
| Grading | |||
| GX | 4 (4.8%) | 21 (14.4%) | |
| G1 | 0 (0.0%) | 1 (0.7%) | |
| G2 | 59 (71.1%) | 101 (69.2%) | |
| G3 | 20 (24.1%) | 23 (15.8%) | 0.072 |
| Response to CCRT | |||
| CR | 13 (15.7%) | 9 (6.2%) | |
| PR | 46 (55.4%) | 66 (45.2%) | |
| SD | 11 (13.3%) | 24 (16.4%) | |
| PD | 10 (12.0%) | 39 (26.7%) | |
| Not assessed | 3 (3.6%) | 8 (5.5%) | 0.016 |
| Pathologic CR ( | 3/30 (10%) | 6/54 (11.1%) | 0.875 |
Abbreviations: 5‐FU, 5‐fluorouracil; CCRT, concurrent chemoradiotherapy; CR, complete remission; ECOG, Eastern Cooperative Oncology Group; G1, grade 1 well‐differentiated; G2, moderately differentiated; G3, poorly differentiated; PC, paclitaxel plus carboplatin; PD, progressive disease; PF, cisplatin+5‐fluorouracil; PR, partial response; SD, stable disease; SqCC, squamous cell carcinoma.
Other pathology includes one sarcomatoid carcinoma and one basaloid carcinoma.
Early stage (stage IIa–IIb) patients did not receive conventional surgery because of a medically inoperable status or primary location at the cervical esophagus.
FIGURE 2Kaplan–Meier survival curves of the two groups. The patients who received chemoradiotherapy using paclitaxel plus carboplatin (PC group) achieved significantly longer progression‐free survival (PFS, p = 0.002) (A) and overall survival (OS, p = 0.019) (B) than those who received cisplatin plus 5‐fluorouracil (PF group). Surgery after concurrent chemoradiotherapy was associated with a significantly better PFS (p < 0.001) (C) and OS (p < 0.001) (D). A cumulative radiation dose of 41.4 Gy was not related to PFS (p = 0.349) (E), but associated with significantly better OS (p = 0.018) (F)
Univariate and multivariate analyses
| Factors | Progression‐free survival | Overall survival | ||||||
|---|---|---|---|---|---|---|---|---|
| Univariate | Multivariate | Univariate | Multivariate | |||||
|
| HR (95% CI) |
| HR (95% CI) |
| HR (95% CI) |
| HR (95% CI) | |
| Age | 0.433 | 0.993 (0.977–1.010) | 0.771 | 0.998 (0.984–1.012) | ||||
| Sex (Male vs. female) | 0.148 | 1.694 (0.829–3.463) | 0.078 | 1.695 (0.943–3.049) | 0.044 | 1.831 (1.016–3.303) | ||
| ECOG PS | 0.555 | 1.099 (0.803–1.503) | 0.117 | 1.246 (0.946–1.641) | ||||
| AJCC stage | <0.001 | 1.466 (1.187–1.810) | 0.005 | 1.347 (1.096–1.657) | 0.001 | 1.368 (1.139–1.642) | 0.007 | 1.282 (1.069–1.537) |
| Tumor location | 0.159 | 0.888 (0.752–1.048) | 0.349 | 0.933 (0.806–1.079) | ||||
| Histology (SqCC vs. non‐SqCC) | 0.629 | 0.84 5 (0.427–1.673) | 0.780 | 1.080 (0.629–1.854) | ||||
| RT dose (≥41.4 Gy vs. <41.4 Gy) | 0.352 | 0.781 (0.464–1.314) | 0.020 | 0.600 (0.390–0.922) | 0.047 | 0.640 (0.413–0.993) | ||
| Surgery (yes vs. no) | <0.001 | 0.397 (0.278–0.567) | <0.001 | 0.417 (0.289–0.600) | <0.001 | 0.384 (0.281–0.525) | <0.001 | 0.412 (0.298–0.570) |
| Treatment regimen (PF vs. PC) | 0.003 | 1.749 (1.217–2.514) | 0.001 | 1.840 (1.275–2.656) | 0.020 | 1.436 (1.058–1.949) | 0.009 | 1.514 (1.109–2.067) |
All the factors in the univariate analysis were examined in the multivariate model. Only factors shown to be significant in the multivariate analysis are listed in the table.
Literature review of two‐arm primary/definitive concurrent chemoradiotherapy studies in esophageal cancer
| Author | Year | Country | Design | Phase | Resectability | Number of patients | Arms | Regimens and results | RT dose (Gy) | Ref. |
|---|---|---|---|---|---|---|---|---|---|---|
| Taxane‐platinum regimens | ||||||||||
| Definitive chemoradiotherapy | ||||||||||
| Tamaki et al. | 2018 | Japan | RS | NA | U | 38+83 | 2 | DCF>PF | 60 | [ |
| Fang et al. | 2017 | China | RS | NA | U | 124+79 | 2 | P‐S1=PC | 60 | [ |
| Münch et al. | 2018 | Germany | RS | NA | U | 25+20 | 2 | PF=PC | 54 | [ |
| Qu et al. | 2017 | Canada | RS | NA | U | 34+13+26 | 3 | PF=CF>PC | 50 | [ |
| Honing et al. | 2014 | Netherlands | RS | NA | U | 47+55 | 2 | PF=PC | 50.4 | [ |
| Current study | 2020 | Taiwan | RS | NA | Inoperable | 83+146 | 2 | PC>PF | 41.4–50.4 | |
| Neoadjuvant chemoradiotherapy | ||||||||||
| van Hagen et al. | 2012 | Netherlands |
| III | R | 178+188 | 2 |
PC +surgery > surgery alone | 41.4 | [ |
| Xi et al. | 2017 | China | RS | NA | R | 32+98 | 2 | DP>PF | 40 | [ |
| Münch et al. | 2017 | Germany | RS | NA | R | 31+20 | 2 | PC=PF | 41.4 | [ |
| Haisley et al. | 2017 | Germany | RS | NA | R | 87+55 | 2 | PF>PC | 50.4 | [ |
| Blom et al. | 2014 | Netherlands | RS | NA | R | 73+92 | 2 | PF=PC | 41.4–50.4 | [ |
| Non‐taxane‐containing regimens in the neoadjuvant setting or in chemoradiotherapy | ||||||||||
| Conroy et al. | 2014 | France | PS | III | U | 134+133 | 2 | FOLFOX=PF | 50 | [ |
| Alderson et al. | 2017 | UK | PS | III | R | 451+446 | 2 | ECX=PF | no RT | [ |
| Yoon et al. | 2015 | Korea | PS | II | R | 47+50 | 2 | ICT>no ICT | 46 | [ |
| von Döbeln GA et al. | 2019 | Sweden, Norway | PS | II | R | 90+91 | 2 | nCRT=no nCRT | 40 | [ |
| Xing et al. | 2014 | China | RS | N/A | U | 40+35 | 2 | CCRT=SCRT | 54–60 | [ |
| Suh et al. | 2014 | Korea | RS | N/A | U | 77+49 | 2 | CCRT RT dose high>low | 54 | [ |
| Chen et al. | 2018 | China | RS | N/A | U | 49+41 | 2 | CCRT=RT | 56 | [ |
| Li et al. | 2017 | China | RS | N/A | U | 29+31 | 2 | CCRT (AP=PC) | 59.6 | [ |
Abbreviations: AP, pemetrexed plus cisplatin; CCRT, concurrent chemoradiotherapy; CF, carboplatin plus 5‐fluorouracil; DCF, docetaxel, cisplatin, 5‐fluorouracil; dCRT, definitive chemoradiotherapy; DP, docetaxel plus cisplatin; ECX, epirubicin plus cisplatin plus capecitabine; ICT, induction chemotherapy; nCRT, neoadjuvant chemoradiotherapy; PC, paclitaxel plus carboplatin; PF, cisplatin plus 5‐fluorouracil; PS, prospective; P‐S1, cisplatin plus TS‐1; R, resectable; RS, retrospective; RT, radiotherapy; SCRT, sequential chemoradiotherapy; U, unresectable.