Docetaxel in the Treatment of Esophageal Cancer

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Esophageal cancer is the ninth most common malignancy in the world and the seventh leading cause of death in American men. Because symptoms are often intermittent and vague, patients typically present at an advanced stage, with limited survival. In operable patients, standard care includes surgery with or without adjuvant chemotherapy and radiotherapy; chemotherapy and radiotherapy is the standard care for inoperable disease. Docetaxel, a taxane that promotes polymerization of tubules and inhibits depolymerization of microtubules, has shown in vitro and in vivo antitumor effects on human gastric cell lines and gastric cancer xenografts. These antitumor effects have led to the evaluation of docetaxel as a single agent and in combination with other agents and modalities in patients with esophageal cancer. Results of relevant trials are reviewed herein.

Section snippets

Trials of Single-Agent Docetaxel

A number of phase II trials have evaluated the safety and efficacy of docetaxel as a single agent in the treatment of esophageal cancer (Table 1).22, 23, 24, 25, 26, 27 Docetaxel was administered intravenously (IV) once every 3 weeks in doses ranging from 6023 to 100 mg/m2,24, 25, 26 with prophylactic administration of 5 μg/kg granulocyte colony-stimulating factor (G-CSF) in one study.25 The most common grade III or IV toxicities included neutropenia, accompanied in some cases by fever.

Docetaxel-Based Combination Regimens for Metastatic or Advanced Disease

Docetaxel has been evaluated in combination with other chemotherapeutic agents for the treatment of esophageal cancer in the metastatic/advanced disease setting (Table 2). Although phase I trials included combinations with a multitude of chemotherapeutic agents (eg, gemcitabine, 5-FU, ifosfamide, lonafarnib, carboplatin, capecitabine, oblimersen, thalidomide),28, 29, 30, 32, 33, 34, 35, 36, 37, 55 phase II data for docetaxel-based combination chemotherapy for metastatic/advanced esophageal

Docetaxel-Based Neoadjuvant and Adjuvant Regimens

Neoadjuvant (induction) therapy before surgery may reduce tumor bulk and improve surgical response, especially in patients with locally advanced operable cancers, while adjuvant therapy may reduce the incidence of local recurrence and distant metastasis. Docetaxel has been evaluated as part of both neoadjuvant and adjuvant therapy (Table 4).44, 45

Summary

Phase I trials of docetaxel-based combination regimens with antimetabolites (gemcitabine, 5-FU), other chemotherapy agents (ifosfamide), and radiation therapy have been encouraging, with the establishment of the MTD in most of these regimens. Phase II trials of docetaxel-based combination regimens (5-FU, irinotecan) have shown antitumor activity in patients with previously treated or untreated esophageal cancer and manageable toxicity profiles. Furthermore, the combined-modality approach of

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    Supported by Aventis Pharmaceuticals, Bridgewater, NJ.

    Dr Rigas has received research grant support from Abbott, Amgen, Aventis, Bristol-Myers Squibb, Genentech, GlaxoSmithKline, Ligand, Merck, Ortho Biotech, OSI, Pfizer, and Roche; he is a consultant for Amgen, Bayer, GlaxoSmithKline, and Ligand. Dr Dragnev has received research grant support from Amgen, Abbott, Genentech and Ligand.

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