Survival following intensive preoperative combined modality therapy with paclitaxel, cisplatin, 5-fluorouracil, and radiation in resectable esophageal carcinoma: a phase I report.
OBJECTIVE
To assess the benefits of aggressive chemoradiation therapy followed by surgery in resectable esophageal carcinoma.


METHODS
Twenty-nine patients with resectable carcinoma were treated with 60 Gy of radiation (2 Gy daily for 6 weeks) and concurrent chemotherapy consisting of continuous infusion of 5-fluorouracil (200-225 mg/m(2)/d), paclitaxel (25, 40, 50, or 60 mg/m(2)) weekly over 1 hour, and cisplatin (25 mg/m(2)) weekly immediately following paclitaxel throughout radiation. Patients received either 4 cycles of postoperative paclitaxel 175 mg/m(2) over 3 hours and cisplatin 75 mg/m(2) every 3 weeks or paclitaxel 175 mg/m(2) over 3 hours and cisplatin 75 mg/m(2) every 3 weeks prior to the initiation of chemoradiation. After induction therapy and restaging, esophagectomy was performed 4 to 6 weeks later.


RESULTS
Twenty-seven patients were eligible for study (26 men, 23 with adenocarcinoma). Median age was 58 years (range 30-73). The maximum tolerated dose combination was paclitaxel 50 mg/m(2) over 1 hour weekly, cisplatin 25 mg/m(2) over 1 hour weekly, 5-fluorouracil 200 mg/m(2)/d by continuous infusion throughout radiotherapy and radiation to 60 Gy. Twenty-two patients completed therapy and underwent surgical resection. Four patients had complete pathological responses and 18 had partial responses with no mortality. The commonest dose-limiting toxicity was mucositis and esophagitis (n = 7). Median follow-up of 27 patients was 150 weeks (range 7-303). At 2-year follow-up 16/27 (59%) were alive and 15/27 (56%) were free of disease. At 4-year follow-up 12/27 (44%) were alive and free of disease. Median follow-up of 22 patients undergoing esophagectomy was 205 weeks (range 26-303). At 4-year follow-up 10/22 (45%) were alive and free of disease. For the 18 patients treated at or above the maximum tolerated dose, median follow-up was 151 weeks (range 35-206) and at 3-year follow-up 9/18 (50%) were alive and free of disease.


CONCLUSIONS
Aggressive combined modality therapy of esophageal carcinoma was associated with excellent long-term survival in this phase I trial.
Goldberg
Melvyn
M
Fox Chase Cancer Center, Division of Thoracic Surgical Oncology, 7701 Burholme Ave, Philadelphia, PA 19111, USA. M_Goldberg@fccc.edu
Farma
Jeffrey
J
Lampert
Craig
C
Colarusso
Patrick
P
Coia
Lawrence
L
Frucht
Harold
H
Goosenberg
Eric
E
Beard
Mary
M
Weiner
Louis M
LM
D000230:Adenocarcinoma / Q000628:therapy; D000328:Adult; D000368:Aged; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage; D000970:Antineoplastic Agents / Q000008:administration & dosage; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage*; D018196:Carcinoma, Adenosquamous / Q000628:therapy; D002294:Carcinoma, Squamous Cell / Q000628:therapy; D002945:Cisplatin / Q000008:administration & dosage; D004334:Drug Administration Schedule; D004938:Esophageal Neoplasms / Q000401:mortality* / Q000532:radiotherapy / Q000628:therapy*; D016629:Esophagectomy; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D017239:Paclitaxel / Q000008:administration & dosage; D011300:Preoperative Care; D015996:Survival Rate
D000964:Antimetabolites, Antineoplastic; D000970:Antineoplastic Agents; D000972:Antineoplastic Agents, Phytogenic; D017239:Paclitaxel; D002945:Cisplatin; D005472:Fluorouracil