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

Ajani, Jaffer A.

doi:10.1159/000137836

Cited by 3 publications

(4 citation statements)

References 21 publications

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“…This trend is not likely to subside. Our current study, a previous randomized phase 2 trial,18 and recent retrospective reviews15, 25‐27 suggest that the second cytotoxic could be a platinum compound, taxane, or camptothecin. The current thrust is to identify a cytotoxic combination regimen that is safe and provides a platform in which to include a biologic (biochemoradiotherapy).…”

Section: Discussionmentioning

confidence: 55%

“…Interest in the addition of a biologic agent is increasing,41 and some studies have been reported to date 40. Based on a recent study,18 our baseline regimen is a combination of a fluoropyrimidine and taxane and it has allowed for the incorporation of a biologic agent in an ongoing trial (available at: http://www.clinicaltrials.gov/ accessed November 2009; NCT00561197).…”

Section: Discussionmentioning

confidence: 99%

“…Although cisplatin and 5–fluorouracil have been most frequently incorporated with chemoradiotherapy for esophageal cancer, the value and morbidity imparted by some of these agents has been a subject of investigation 18. Most frequently, 2 agents from the 4 classes of cytotoxics (flouropyrimidines, platinols, camptothecins, and taxanes) are combined with radiotherapy.…”

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confidence: 99%

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Trimodality therapy without a platinum compound for localized carcinoma of the esophagus and gastroesophageal junction

Ajani

Correa

Walsh

et al. 2010

Cancer

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BACKGROUND:The use of platinum-based chemoradiation for esophageal cancer is routine, but it is unclear which class of cytotoxic are optimum. It was hypothesized that chemoradiotherapy with fluoropyrimidine, taxane, and camptothecin would have preserved or improved efficacy with no compromise in safety. METHODS: Patients with histologically confirmed, resectable esophageal carcinoma were eligible. In addition to other tests, a baseline endoscopic ultrasonography (EUS) was obtained. Patients were medically fit and had near-normal organ functions. Patients received docetaxel and irinotecan, plus 5-fluorouracil as induction therapy and then the same cytotoxics with 50.4 grays of radiotherapy followed by an attempted surgery. Pathologic complete response (pathCR) at a rate of 20% was the primary endpoint. The pathCR and R0 resection were correlated with overall survival (OS). Safety was documented. RESULTS: Fifty-five patients were enrolled. Seven were women, and the median age was 56 years. Fifty-three (96%) patients had EUST3, and 41 (75%) had EUSN1 disease. Forty-three (78%) patients underwent surgery, 20% achieved a pathCR, and 76.4% underwent an R0 resection. The median survival (n ¼ 55 patients) was 43.3 months (range, 19-75 months). Baseline clinical parameters were not found to be predictive of OS; however, patients with a pathCR (P ¼ .005) and who underwent R0 resection (P .0001) had an improved OS. There was 1 treatmentrelated postsurgical death reported. Grade 3 or 4 toxicity (graded according to the National Cancer Institute Common Toxicity Criteria [version 2.0]) was observed in 62% of patients. CONCLUSIONS: The results of the current study documented that this 3-drug, noncisplatin-based chemoradiotherapy was feasible, safe, and active but not better than the published cisplatin-based chemoradiotherapy. A fluoropyrimidine and another cytotoxic (from any class) may be adequate to establish a baseline chemoradiotherapy regimen to combine biologics.

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Section: Discussionmentioning

confidence: 55%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

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Trimodality therapy without a platinum compound for localized carcinoma of the esophagus and gastroesophageal junction

Ajani

Correa

Walsh

et al. 2010

Cancer

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“…Although platinums and fluoropyrimidines have historically been used to treat gastroesophageal cancer, paclitaxel alone or in combination with other agents such as 5 FU or cisplatin is a current therapy (1). Studies have suggested that paclitaxel is efficacious in patients with ESCC and its use results in improvements in clinical outcomes (1,10,11). However, patients who are treated with paclitaxel often relapse or do not respond to the treatment.…”

Section: Introductionmentioning

confidence: 99%

Combination treatment with paclitaxel and doxorubicin inhibits growth of human esophageal squamous cancer cells by inactivation of Akt

Lee

et al. 2013

Oncology Reports

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Despite the fact that paclitaxel and doxorubicin are widely used as chemotherapy agents against several types of cancer, their combined effects on esophageal squamous cell carcinoma (ESCC) have never been fully elucidated. The present study was designed to investigate the biological effects of paclitaxel and doxorubicin in ESCC cells. Combination treatment with paclitaxel and doxorubicin significantly inhibited the proliferation of TE-12 cells in a dose-and time-dependent manner compared to treatment with paclitaxel or doxorubicin alone. FACS analysis showed that the percentage of cells in the G2/M phase was significantly increased at 12 h after treatment with the combination. Increased p-cdc2, p-Wee1 and p53 protein levels were observed, while Akt activation was suppressed by combination treatment with paclitaxel and doxorubicin. In addition, treatment with paclitaxel plus doxorubicin significantly increased apoptosis as indicated by increased cleaved poly(ADP-ribose) polymerase and cleaved caspase-7 and -9 levels. These results suggest that combination treatment with paclitaxel and doxorubicin induced G2/M cell cycle arrest and apoptosis in human ESCC cells by suppressing Akt activity. These findings highlight the potent apoptotic effect of combination therapy with paclitaxel and doxorubicin in ESCC cells and the potential clinical benefits of these two drugs in esophageal cancer.

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Ajani

2009

JCO

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

Cited by 3 publications

References 21 publications

Trimodality therapy without a platinum compound for localized carcinoma of the esophagus and gastroesophageal junction

Trimodality therapy without a platinum compound for localized carcinoma of the esophagus and gastroesophageal junction

Combination treatment with paclitaxel and doxorubicin inhibits growth of human esophageal squamous cancer cells by inactivation of Akt

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