Phase II evaluation of preoperative chemoradiation and postoperative adjuvant chemotherapy for squamous cell and adenocarcinoma of the esophagus.

PURPOSE: This phase II trial evaluated continuous-infusion cisplatin and fluorouracil (5-FU) with radiotherapy followed by esophagectomy. The objectives of this trial were to determine the complete pathologic response rate, survival rate, toxicity, pattern of failure, and feasibility of administering adjuvant chemotherapy in patients with resectable cancer of the esophagus treated with preoperative chemoradiation. PATIENTS AND METHODS: Patients were staged using computed tomography, endoscopic ultrasound, and laparoscopy. The preoperative treatment plan consisted of continuous intravenous infusion of cisplatin and 5-FU and a total dose of 44 Gy of radiation. Esophagogastrectomy was planned for approximately 4 weeks after the completion of chemoradiotherapy. Paclitaxel and cisplatin were administered as postoperative adjuvant therapy. RESULTS: Forty-two patients were enrolled onto the trial. Of the 39 patients who proceeded to surgery, 29 responded to preoperative treatment: 11 achieved pathologic complete response (CR) and 18 achieved a lower posttreatment stage. Five patients had no change in stage, whereas eight had progressive disease (four with distant metastases and four with increases in the T and N stages). At a median follow-up of 30.2 months, the median survival time has not been reached and the 2-year survival rate is 62%. The median survival of pathologic complete responders has not been reached, whereas the 2-year survival rate of this group is 91% compared with 51% in patients with complete tumor resection with residual tumor (P =.03). CONCLUSION: An excellent survival rate, comparable to that of our prior preoperative trial, was achieved with lower doses of preoperative cisplatin and 5-FU concurrent with radiotherapy.

Increased expression of the epidermal growth factor receptor on human colon carcinoma cells.

Epidermal growth factor (EGF) is a small polypeptide hormone that promotes the growth of cells in culture and elicits the differentiation of epithelial tissues in vivo. The effect of EGF is mediated by a transmembrane receptor that is expressed in increased amounts on some tumor cells. We have used a monoclonal antibody to the EGF receptor to detect increased expression of the receptor on human colon carcinoma cells. All eight of the moderately well-differentiated colon carcinoma cell lines tested and several frozen colon carcinoma tissue sections showed increased expression of the EGF receptor, while five poorly differentiated colon carcinoma cell lines and normal colon tissue sections did not. Increased expression of the EGF receptor on moderately well-differentiated colon carcinoma cells but not on poorly differentiated colon carcinoma cells was also demonstrated by western transfer and iodine 125-labeled EGF binding assays. Increased expression of the EGF receptor on moderately well-differentiated colon carcinoma cells seems to be a useful marker for the differentiation of human colon carcinoma cells. In addition, it might provide a site for adjuvant hormonal therapy or immunotherapy.

Inhibition of rat colon tumor isograft growth with dequalinium chloride.

In searching for a new approach to the systemic treatment of colorectal carcinoma, we have observed that certain lipophilic cationic compounds are accumulated and retained for a significantly longer period in the mitochondria of living carcinoma cells than in normal cells or sarcoma cells. We report the in vivo therapeutic effect of one of these compounds, dequalinium chloride, on the W163 rat colon carcinoma isograft, which grows rapidly in Wistar/Furth rats after primary tumor implantation, and which recurs rapidly after primary tumor resection. In the primary transplant model, tumors were implanted, and daily dequalinium chloride treatments were begun the following day in doses ranging from 1 to 10 mg/kg. In the recurrence model, isografts were implanted, allowed to grow for one week, and then all gross tumor was resected. Dequalinium chloride was administered in varying daily doses starting the day after resection. In both models, tumor was removed on day 11 after implantation or resection. At sublethal doses, dequalinium chloride significantly inhibited primary tumor growth to 60% that of controls and recurrent tumor growth to 50% that of controls. We propose that this unique biologic approach of targeting carcinoma mitochondria with lipophilic cationic compounds may provide a major new opportunity for treating colorectal carcinoma.