Preoperative mitomycin, ifosfamide, and cisplatin followed by esophagectomy in squamous cell carcinoma of the esophagus: pathologic complete response induced by chemotherapy leads to long-term survival.
OBJECTIVE
Squamous cell carcinoma of the esophagus remains an aggressive disease with a poor prognosis, even after curative-intent surgery. This article analyzes the impact of preoperative chemotherapy with mitomycin, ifosfamide, and cisplatin (MIC) on a cohort of 68 patients.


METHODS
From 1988 to 1994, 68 patients with potentially operable squamous cell carcinoma of the esophagus were entered onto two phase II trials of neoadjuvant chemotherapy with mitomycin 6 mg/m2, ifosfamide 3 g/m2, and cisplatin 50 mg/m2 and received between two and four cycles of treatment at 3-weekly intervals. Two patients were removed from the analysis when they were found to have malignancy other than squamous cell carcinoma of the esophagus.


RESULTS
Forty (61%) of 66 patients had a radiologic response to chemotherapy (18 complete responses and 22 partial responses), and 52 (79%) of 66 patients went on to have the primary tumor resected. There were nine pathologic complete responders, seven of whom remain fit and well after at least 60 months of follow-up. The overall median survival was 12.4 months (95% confidence interval, 9.6 to 18.8 months). The complete response and node-negative patients survived significantly longer than those in other categories (log-rank chi2 = 18.8; P <.001): on average 13 months longer than the node-positive or nonresected category (22.0 v 9.4 months). The toxicity of the regimen was low.


CONCLUSIONS
MIC is an easily administered, well-tolerated, and efficacious regimen as neoadjuvant therapy for patients with squamous cell carcinoma of the esophagus. These results warrant further investigation.
Birmingham Heartlands Hospital and Cancer Research UK Trials Unit, Institute of Cancer Research, University of Birmingham, United Kingdom. jane.darnton@heartsol.wmids.nhs.uk
S J
SJ
Darnton
V R
VR
Archer
D D
DD
Stocken
P J
PJ
Mulholland
A G
AG
Casson
D R
DR
Ferry
D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000627:therapeutic use*; D002294:Carcinoma, Squamous Cell / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology / Q000601:surgery*; D002945:Cisplatin / Q000008:administration & dosage; D015331:Cohort Studies; D003131:Combined Modality Therapy; D004334:Drug Administration Schedule; D004938:Esophageal Neoplasms / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology / Q000601:surgery*; D016629:Esophagectomy; D005260:Female; D006801:Humans; D007069:Ifosfamide / Q000008:administration & dosage; D008297:Male; D008875:Middle Aged; D016685:Mitomycin / Q000008:administration & dosage; D020360:Neoadjuvant Therapy; D009364:Neoplasm Recurrence, Local / Q000000981:diagnostic imaging / Q000401:mortality / Q000473:pathology; D009660:Northern Ireland; D011859:Radiography; D016019:Survival Analysis; D016896:Treatment Outcome
D016685:Mitomycin; D002945:Cisplatin; D007069:Ifosfamide