Long-term follow-up of a pilot phase II study with neoadjuvant epidoxorubicin, etoposide and cisplatin in gastric cancer.
OBJECTIVE
The prognosis in T3-T4 or N+ gastric cancer is dismal, and the role of adjuvant therapy remains uncertain. Neoadjuvant chemotherapy could improve both resectability and survival. Here, we report the results of the long-term follow-up of a pilot study aimed at evaluating a neoadjuvant treatment in a group of patients carefully staged by computed tomography (CT), endoscopic ultrasound and laparoscopy.


METHODS
Twenty-five stage II-III patients with histologically proven gastric adenocarcinoma were enrolled in the study. All patients gave informed consent and were thoroughly staged. Patients were treated with epidoxorubicin (40 mg/m2 i.v.) on days 1 and 4, etoposide (VP-16; 100 mg/m2) on days 1, 3 and 4 and cisplatinum (80 mg/m2) on day 2, every 21-28 days for 3 pre-operative cycles before CT clinical restaging followed by laparotomy and D2 gastrectomy. Three further cycles of chemotherapy were planned after radical surgery.


RESULTS
Twenty-four patients received the planned pre-operative chemotherapy and underwent surgical resection; total (13 patients) or subtotal (7 patients) R0 D2 gastrectomy was possible in 20 patients. One patient died as a result of gastric bleeding. Perioperative complications occurred in 5 patients (failure of anastomosis in 1 patient and wound infection in the other 4). The pathologic response rate included 7 partial responses (29.1%) and 10 patients with stable disease (41.7%). The main toxicity was grade 3/4 neutropenia (68%), which occurred more frequently during the postoperative chemotherapy, and fatigue (68%). Fever or infection, however, were never observed. The median disease-free survival was 37 months, and median survival has not been reached after 40 months of median follow-up. One-, 2- and 3-year survival rates were 80, 64 and 60%, respectively.


CONCLUSIONS
The notable long-term survival in the present study suggests a comparison between the neoadjuvant approach, including new drug combinations, and adjuvant chemo- or chemoradio-therapy in locally advanced gastric cancer.
Barone
C
C
Unit of Medical Oncology, Department of Internal Medicine, Università Cattolica del S. Cuore, Roma, Italy. carlobarone@rm.unicatt.it
Cassano
A
A
Pozzo
C
C
D'Ugo
D
D
Schinzari
G
G
Persiani
R
R
Basso
M
M
Brunetti
I M
IM
Longo
R
R
Picciocchi
A
A
D000230:Adenocarcinoma / Q000188:drug therapy* / Q000556:secondary / Q000601:surgery; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D002945:Cisplatin / Q000008:administration & dosage; D018572:Disease-Free Survival; D015251:Epirubicin / Q000008:administration & dosage / Q000031:analogs & derivatives*; D005047:Etoposide / Q000008:administration & dosage; D005260:Female; D005500:Follow-Up Studies; D005965:Glucuronates / Q000008:administration & dosage; D006801:Humans; D008297:Male; D008875:Middle Aged; D020360:Neoadjuvant Therapy / Q000379:methods*; D009367:Neoplasm Staging; D010865:Pilot Projects; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000601:surgery; D016019:Survival Analysis; D013997:Time Factors; D016896:Treatment Outcome
D005965:Glucuronates; C074868:epidoxorubicin glucuronide; D015251:Epirubicin; D005047:Etoposide; D002945:Cisplatin