Neoadjuvant chemoradiation followed by surgery versus surgery alone for patients with adenocarcinoma or squamous cell carcinoma of the esophagus (CROSS).
BACKGROUND
A surgical resection is currently the preferred treatment for esophageal cancer if the tumor is considered to be resectable without evidence of distant metastases (cT1-3 N0-1 M0). A high percentage of irradical resections is reported in studies using neoadjuvant chemotherapy followed by surgery versus surgery alone and in trials in which patients are treated with surgery alone. Improvement of locoregional control by using neoadjuvant chemoradiotherapy might therefore improve the prognosis in these patients. We previously reported that after neoadjuvant chemoradiotherapy with weekly administrations of Carboplatin and Paclitaxel combined with concurrent radiotherapy nearly always a complete R0-resection could be performed. The concept that this neoadjuvant chemoradiotherapy regimen improves overall survival has, however, to be proven in a randomized phase III trial.


METHODS
The CROSS trial is a multicenter, randomized phase III, clinical trial. The study compares neoadjuvant chemoradiotherapy followed by surgery with surgery alone in patients with potentially curable esophageal cancer, with inclusion of 175 patients per arm.The objectives of the CROSS trial are to compare median survival rates and quality of life (before, during and after treatment), pathological responses, progression free survival, the number of R0 resections, treatment toxicity and costs between patients treated with neoadjuvant chemoradiotherapy followed by surgery with surgery alone for surgically resectable esophageal adenocarcinoma or squamous cell carcinoma. Over a 5 week period concurrent chemoradiotherapy will be applied on an outpatient basis. Paclitaxel (50 mg/m2) and Carboplatin (Area-Under-Curve = 2) are administered by i.v. infusion on days 1, 8, 15, 22, and 29. External beam radiation with a total dose of 41.4 Gy is given in 23 fractions of 1.8 Gy, 5 fractions a week. After completion of the protocol, patients will be followed up every 3 months for the first year, every 6 months for the second year, and then at the end of each year until 5 years after treatment. Quality of life questionnaires will be filled out during the first year of follow-up.


CONCLUSIONS
This study will contribute to the evidence on any benefits of neoadjuvant treatment in esophageal cancer patients using a promising chemoradiotherapy regimen.


BACKGROUND
ISRCTN80832026.
van Heijl
M
M
Department of Surgery, Academic Medical Center, Amsterdam, The Netherlands. m.vanheijl@amc.uva.nl
van Lanschot
J J B
JJ
Koppert
L B
LB
van Berge Henegouwen
M I
MI
Muller
K
K
Steyerberg
E W
EW
van Dekken
H
H
Wijnhoven
B P L
BP
Tilanus
H W
HW
Richel
D J
DJ
Busch
O R C
OR
Bartelsman
J F
JF
Koning
C C E
CC
Offerhaus
G J
GJ
van der Gaast
A
A
D000230:Adenocarcinoma / Q000188:drug therapy / Q000532:radiotherapy / Q000601:surgery* / Q000628:therapy*; D000970:Antineoplastic Agents / Q000627:therapeutic use; D000972:Antineoplastic Agents, Phytogenic / Q000627:therapeutic use; D016190:Carboplatin / Q000627:therapeutic use; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy / Q000532:radiotherapy / Q000601:surgery* / Q000628:therapy*; D018450:Disease Progression; D004938:Esophageal Neoplasms / Q000188:drug therapy / Q000532:radiotherapy / Q000601:surgery* / Q000628:therapy*; D006801:Humans; D020360:Neoadjuvant Therapy; D017239:Paclitaxel / Q000627:therapeutic use; D018579:Patient Selection; D011788:Quality of Life; D011879:Radiotherapy Dosage; D012107:Research Design
D000970:Antineoplastic Agents; D000972:Antineoplastic Agents, Phytogenic; D016190:Carboplatin; D017239:Paclitaxel