Phase II study of preoperative pemetrexed, carboplatin, and radiation followed by surgery for locally advanced esophageal cancer and gastroesophageal junction tumors.
BACKGROUND
Based on favorable preliminary clinical data and the need to identify effective, well-tolerated neoadjuvant regimens for patients with locally advanced esophageal cancer, this clinical trial was undertaken.


METHODS
This phase II study tested 500 mg/m neoadjuvant pemetrexed intravenously and carboplatin with an area under the curve of 6 intravenously on days 1 and 22 in conjunction with concomitant radiation of 5040 centigray, which was given in 28 daily fractions of 180 centigray. The primary endpoint was the rate of pathologic complete response.


RESULTS
This trial closed early because, during an interim analysis, the primary endpoint fell short. However, 26 eligible patients were accrued. Twenty (74%) were men. Performance scores of 0, 1, and 2 were seen in 16 (59%), 9 (33%), and 2 (7%), respectively. Among eligible patients, 6 of 26 (23%; 95% confidence interval 9-44%) demonstrated a pathologic complete response. Twenty-two underwent a complete cancer resection. The median survival was 17.8 months (95% confidence interval: 12.2-30.7 months). In the neoadjuvant setting, 22 patients had at least one grade 3 or worse adverse event, and 8 patients had at least one grade 4 event. Postoperatively (within 30 days of surgery), there were three deaths, one grade 4 event (thrombosis), and three grade 3 events.


CONCLUSIONS
The neoadjuvant regimen tested within this phase II trial demonstrated antineoplastic activity but fell short of yielding a complete pathologic response rate that merits further testing.
Jatoi
Aminah
A
Department of Oncology, Mayo Clinic Rochester, Rochester, Minnesota 55905, USA. Jatoi.aminah@mayo.edu
Soori
Gamini
G
Foster
Nathan R
NR
Hiatt
Bradley K
BK
Knost
James A
JA
Fitch
Tom R
TR
Callister
Matthew D
MD
Nichols
Francis C
FC
Husted
Tim M
TM
Alberts
Steven R
SR
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D016190:Carboplatin / Q000008:administration & dosage; D003131:Combined Modality Therapy; D004938:Esophageal Neoplasms / Q000628:therapy*; D004943:Esophagogastric Junction; D005260:Female; D005971:Glutamates / Q000008:administration & dosage; D006147:Guanine / Q000008:administration & dosage / Q000031:analogs & derivatives; D006801:Humans; D008297:Male; D008875:Middle Aged; D000068437:Pemetrexed; D011879:Radiotherapy Dosage
D005971:Glutamates; D000068437:Pemetrexed; D006147:Guanine; D016190:Carboplatin