David H. Ilson, MD, PhD

Dr. Krasna has written an overview of multimodality therapy in esophageal cancer, with a particular focus on aspects related to staging and surgical care. The optimal management of locally advanced esophageal cancer remains a subject of controversy and active debate. However, there is now a clear consensus that surgery alone is inadequate therapy for patients with T3 or node-positive disease.

Dr. Pohl and colleagues have provided a comprehensive and well written overview of the current landscape of targeted agents and chemotherapy in advanced colorectal cancer.

Esophageal cancer is a rare but highly virulent malignancy in theUnited States, and adenocarcinoma of the esophagus has had the mostrapid rate of increase of any solid tumor malignancy. Systemic metastaticdisease is present in 50% of patients at diagnosis. In the remaining50% presenting with local regional disease, systemic metastatic diseasewill develop in the vast majority of these patients.

The limited effectiveness of chemotherapy in esophageal cancerused to palliate metastatic disease or to combine with radiotherapy inlocally advanced disease has prompted the evaluation of new systemicagents. Irinotecan (CPT-11, Camptosar) has shown promising activityin a number of gastrointestinal cancers, including esophageal cancer.The phase II evaluation of the combination of weekly irinotecan andcisplatin has shown encouraging response rates exceeding 30% to 50%in esophageal and gastric cancer. Novel regimens include the combinationof irinotecan with mitomycin (Mutamycin), the taxanes docetaxel(Taxotere) and paclitaxel, and continuous infusion fluorouracil(5-FU). Irinotecan is an active radiosensitizer, and trials have evaluatedthe combination of irinotecan with concurrent radiotherapy. We completeda phase I trial combining weekly irinotecan, cisplatin, andconcurrent radiotherapy in locally advanced esophageal cancer. Minimaltoxicity has been observed, with no grade 3/4 esophagitis ordiarrhea, and hematologic toxicity was also surprisingly minimal. Fulldoses of weekly irinotecan (65 mg/m2) and cisplatin (30 mg/m2) could becombined safely with concurrent radiotherapy, with a significant rate ofpathologic complete response. Phase II evaluation of this chemoradiotherapyregimen as preoperative therapy is planned at single institutionsand at the cooperative group level in the United States. Furtherphase I and II investigation of combined irinotecan, cisplatin, andconcurrent radiation is ongoing with the addition of targeted agents,including celecoxib (Celebrex), cetuximab (Erbitux), and bevacizumab(Avastin). Alternative combinations of irinotecan with radiotherapy,including the addition of docetaxel and continuous infusion 5-FU, arealso undergoing phase I and II evaluation.

The limited effectiveness of currently available chemotherapy in the treatment of advanced esophageal cancer, and the poor survival achieved in locally advanced disease with combined chemoradiotherapy with or without surgery, have prompted the evaluation of new agents. Irinotecan (CPT-11, Camptosar) has promising single-agent activity in gastrointestinal cancers.

Irinotecan (CPT-11, Camptosar) a topoisomerase I inhibitor derived from the Chinese shrub Camptotheca acuminata, has broad activity in varied gastrointestinal malignancies, including pancreatic, biliary, esophageal

Irinotecan (Camptosar) has shown activity in several solid tumor malignancies, including gastric and pancreatic cancer. In vitro studies suggest antitumor activity in esophageal cancer cell lines. Sequence-dependent synergy

Irinotecan (Camptosar), an active agent in the treatment of fluorouracil-refractory colorectal cancer, has antitumor activity in upper gastrointestinal cancers. Clinical trials from Japan indicate antitumor responses in gastric and

The standard approaches of surgery or radiotherapy cure only a minority of patients with esophageal cancer. Because of these poor results and the frequent systemic pattern of recurrences, combined-modality therapy