Influence of induction chemotherapy and class of cytotoxics on pathologic response and survival after preoperative chemoradiation in patients with carcinoma of the esophagus

Abstract

BACKGROUND.Patients with localized esophageal cancer (LEC) have diverse outcomes (post‒therapy pathologic response, disease‒free survival [DFS], and overall survival [OS]) after preoperative chemoradiation (P‒CTRT), dictated also by inherent molecular heterogeneity. Whether the type of therapy influences the outcomes remains largely unanswered. It is hypothesized that induction chemotherapy (IC) or the type of cytotoxics used would not influence patient outcomes.METHODS.In this retrospective analysis, consecutive patients with LEC who had P‒CTRT were analyzed. Data were collected regarding age, sex, baseline clinical stage, location, type of cytotoxics, post‒therapy pathology, DFS, and OS. IC and the type of cytotoxics used were found to be correlated with DFS, OS, and post‒therapy pathologic response.RESULTS.A total of 180 patients with LEC (119 had IC before P‒CTRT, all had received 5‒fluorouracil, 87 had received a taxane, and 57 had received a platinol) were analyzed. The median survival (MS) of all patients was 57.7 months and the 3‒year and 5‒year OS rates were 65.4% and 46.5%, respectively. The type of therapy appeared to have no influence on the outcome: IC versus no IC (P = .58) or platinol versus taxane versus platinol plus taxane (P = .63). Similarly, the type of pathologic response was not found to be influenced by IC (P = .18) or the type of cytotoxics used (P = .42). The data were similar for DFS.CONCLUSIONS.IC or the type of cytotoxics used with radiation for patients with LEC does not appear to influence OS, DFS, or the type of pathologic response after therapy, suggesting that a plateau has been reached. It remains to be seen whether the use of biochemoradiotherapy can provide an advantage in outcome. Cancer 2008. © 2008 American Cancer Society.

Therapy of Localized Esophageal Cancer: It Is Time to Reengineer Our Investigative Strategies

“…Limitations of this report include: comparison of nonrandomized populations, retrospective nature of the analysis, small number of patients, patients treated in different time frames, and investigator bias. However, their data are consistent with a recent publication from the Duke University on 109 patients [22] and 180 patients from my center [9]. On the other hand, in another unpublished analysis of 360+ patients from my center, the use of a taxane in patients with localized carcinoma of the esophagus treated with preoperative chemoradiation lead to a survival advantage.…”

“…These drugs are added or removed from further investigation based solely on empiricism; we finish the trial and get disappointed as usual. None of us has a clue as to what combination is better and until we do, perhaps we should choose the ones that are well tolerated [9]. Blinded use of targeted agents cannot quench our desire for rapid progress because the targeted agents act only if certain alterations exist within the tumor [10,11].…”

The value of 18F-FDG PET before and after induction chemotherapy for the early prediction of a poor pathologic response to subsequent preoperative chemoradiotherapy in oesophageal adenocarcinoma

“…However, this potential superiority was not found in a retrospective comparative study [17] and two prospective randomized phase II studies [27, 29]. One study suggested that only patients with stage III and IVa (and not stage II) disease who received induction chemotherapy had a significant survival advantage over preoperative CRT alone [16].…”

“…The backbone of induction chemotherapy generally consisted of a fluoropyrimidine (intravenous 5-FU or oral capecitabine) and oxaliplatin, with the addition of either leucovorin (54 % of cases) or docetaxel (37 % of cases) [17, 27]. Other (sporadic) induction chemotherapy regimens included carboplatin/paclitaxel (3 %), cisplatin/paclitaxel (1.5 %), cisplatin/irinotecan (1.5 %), 5-FU monotherapy (1.5 %) and capecitabine/oxaliplatin/epirubicin (1.5 %).…”

MET Amplification Identifies a Small and Aggressive Subgroup of Esophagogastric Adenocarcinoma With Evidence of Responsiveness to Crizotinib

“…5 The prognosis for advanced GEC remains extremely poor, and overall 5-year survival rates are approximate 15%. 1,6 Cytotoxicchemotherapyremainsthemainstay of treatment for patients with incurable disease, 7 and targeted therapeutics are assuming an increasingly important role.…”