Phase II trial of gemcitabine in patients with previously untreated metastatic cancer of the esophagus or gastroesophageal junction

Sandler, Alan; Kindler, Hedy L.; Einhorn, L. H.; Mitchell, E.; Masters, G.; Kraut, Michael; Nicol, Steven J.; Raghavan, Derek

doi:10.1023/a:1008369718242

Cited by 26 publications

(9 citation statements)

References 17 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…At present, gemcitabine is applied in several tumors, mainly pancreatic carcinoma, breast carcinoma, urinary bladder carcinoma, head and neck tumors, nonsmall cell bronchial carcinoma and several gastrointestinal tumors (Sandler et al 2000;Gitlitz et al 2003;Guarneri and Conte 2004;Raguse et al 2005). As the intrahepatic cholangiocarcinoma is morphologically related to the pancreatic carcinoma, the application of gemcitabine is justiWable at least in experimental studies (Verderame et al 2000;Kubicka et al 2001;Tsavaris et al 2004).…”

Section: Survival Function In Group With Microspheresmentioning

confidence: 99%

Hepatic intraarterial chemotherapy with gemcitabine in patients with unresectable cholangiocarcinomas and liver metastases of pancreatic cancer: a clinical study on maximum tolerable dose and treatment efficacy

Vogl

Schwarz

Eichler

et al. 2006

J Cancer Res Clin Oncol

View full text Add to dashboard Cite

show abstract

Section: Survival Function In Group With Microspheresmentioning

confidence: 99%

Hepatic intraarterial chemotherapy with gemcitabine in patients with unresectable cholangiocarcinomas and liver metastases of pancreatic cancer: a clinical study on maximum tolerable dose and treatment efficacy

Vogl

Schwarz

Eichler

et al. 2006

J Cancer Res Clin Oncol

View full text Add to dashboard Cite

show abstract

“…10 Chemotherapy with cisplatin and 5-flurouracil along with radiotherapy has been shown to improve survival 11,12 and new regimens incorporating agents, such as camptothecin, gemcitabine and paclitaxel have been tested. [13][14][15][16] Although survival has been improved by adding chemo-and radiotherapy to surgical resection, it appears that only a subset of patients benefit significantly; overall 5-year survival remains below 50% even in the best of circumstances. 17 One way to improve the treatment and survival of EAC would be to develop novel therapies based on specific molecular targets.…”

mentioning

confidence: 99%

Identification of Fn14/TWEAK receptor as a potential therapeutic target in esophageal adenocarcinoma

Watts

Tran

Berens

et al. 2007

Intl Journal of Cancer

View full text Add to dashboard Cite

Given the poor survival rate and efficacy of current therapy for esophageal adenocarcinoma (EAC), there is a need to identify and develop new therapeutic targets for treatment. Microarray analysis (Affymetrix U133A GeneChips, Robust Multi-Chip Analysis) was used to expression profile 11 normal squamous and 18 Barrett's esophagus biopsies, 7 surgically resected EACs and 3 EAC cell lines. Two hundred transcripts representing potential therapeutic targets were identified using the following criteria: significant overexpression in EAC by analysis of variance (p 5 0.05, Benjamini Hochberg false discovery rate); 3-fold increase in EAC relative to normal and Barrett's esophagus and expression in at least 2 of the 3 EAC cell lines. From the list of potential targets we selected TNFRSF12A/Fn14/TWEAK receptor, a tumor necrosis factor super-family receptor, for further validation based on its reported role in tumor cell survival and potential as a target for therapy. Fn14 protein expression was confirmed in SEG-1 and BIC-1 cell lines, but Fn14 was not found to affect tumor cell survival after exposure to chemotherapeutics as expected. Instead, a novel role in EAC was discovered in transwell assays, in which modulating Fn14 expression affected tumor cell invasion. Fn14's potential as a therapeutic target was further supported by immunohistochemistry on a tissue microarray of patient samples that showed that Fn14 protein expression increased with disease progression in EAC.

show abstract

“…A phase II trial of single agent gemcitabine in metastatic oesophageal cancer showed no activity in the 21 patients treated (Sandler et al, 2000). The Southwest Oncology Group conducted a multicentre phase II trial of gemcitabine 1000 mg m À2 on days 1, 8 and 15, and cisplatin 100 mg m À2 on day 15 of a 28-day cycle in 64 patients with advanced oesophageal cancer.…”

Section: Discussionmentioning

confidence: 99%

Phase II study of gemcitabine and cisplatin in locally advanced/metastatic oesophageal cancer

et al. 2005

View full text Add to dashboard Cite

Palliative chemotherapy for inoperable/metastatic oesophageal cancer has limited activity. This study assesses the feasibility and activity of gemcitabine and cisplatin in this group of patients. In total, 42 patients with locally advanced/metastatic squamous or adenocarcinoma of the oesophagus were treated with gemcitabine 1250 mg m À2 days 1 and 8 and cisplatin 75 mg m À2 day 1 in a 21-day cycle. Interim safety analysis was carried out after the first 19 patients suggested significant toxicity. The dose of gemcitabine was subsequently reduced to 1000 mg m À2 . Patients were assessed for toxicity and response. The median number of treatment cycles per patient was 4 (range 1 -6). Grade 3 -4 neutropenia occurred in 37% of cycles; however, there was only one episode of neutropenic fever. Nonhaematological toxicities included fatigue, nausea and vomiting. Among 32 patients eligible for response, there were three complete responses and 16 partial responses (overall response rate of 45%); nine patients had stable disease. Median survival was 11 months. The response rate appears to be greatest in those with squamous carcinoma compared to adenocarcinoma (71 vs 33%, P ¼ 0.036). The combination of gemcitabine and cisplatin in this schedule has manageable toxicity and significant activity in patients with locally advanced/metastatic oesophageal cancer and is worthy of further study.

show abstract

Phase II trial of gemcitabine in patients with previously untreated metastatic cancer of the esophagus or gastroesophageal junction

Abstract: At the dose and schedule studied it would appear that gemcitabine has no activity in patients with chemotherapy-naïve esophageal carcinoma.

Cited by 26 publications

References 17 publications

Hepatic intraarterial chemotherapy with gemcitabine in patients with unresectable cholangiocarcinomas and liver metastases of pancreatic cancer: a clinical study on maximum tolerable dose and treatment efficacy

Hepatic intraarterial chemotherapy with gemcitabine in patients with unresectable cholangiocarcinomas and liver metastases of pancreatic cancer: a clinical study on maximum tolerable dose and treatment efficacy

Identification of Fn14/TWEAK receptor as a potential therapeutic target in esophageal adenocarcinoma

Phase II study of gemcitabine and cisplatin in locally advanced/metastatic oesophageal cancer

Contact Info

Product

Resources

About