Postoperative adjuvant gemcitabine and concurrent radiation after curative resection of pancreatic head carcinoma: a phase II study

Laethem, Jean‐Luc Van; Demols, A.; Closon, Marie-Thérèse; Collette, M; Polus, Marc; Houbiers, Ghislain; Gastelblum, Pauline; Gelin, Michel; Houtte, Paul Van; Closset, Jean

doi:10.1016/s0360-3016(03)00164-0

Cited by 48 publications

(33 citation statements)

References 18 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…We previously conducted two phase II multicentric studies evaluating (15,16) adjuvant chemoradiotherapy with gemcitabine for completely resected pancreatic adenocarcinoma. Both regimens shared similar designs, were highly feasible, and produced limited toxicity.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Human Equilibrative Nucleoside Transporter 1 and Human Concentrative Nucleoside Transporter 3 Predict Survival after Adjuvant Gemcitabine Therapy in Resected Pancreatic Adenocarcinoma

Maréchal¹,

Mackey²,

Lai

et al. 2009

Clinical Cancer Research

Self Cite

199

159

View full text Add to dashboard Cite

Purpose: Gemcitabine is a promising adjuvant treatment for patients with resected pancreatic adenocarcinoma and its use in combination with radiotherapy is under exploration. Human equilibrative nucleoside transporter 1(hENT1) and human concentrative nucleoside transporter (hCNT) 1and 3 are the major transporters responsible for 2 ¶,2 ¶-difluoro-2-deoxycytidine (gemcitabine) uptake into cells. The aim of this study was to determine patients' outcome according to the expression of hENT1 and hCNT3 in tumoral cells after postoperative gemcitabine-based chemoradiation regimen. Experimental Design: We studied tumor blocks from 45 pancreatic adenocarcinoma patients treated with gemcitabine-based chemoradiation after curative resection and assessed hENT1and hCNT3 expression using immunohistochemistry. Results: When adjusted for the effects of lymph node ratio and tumor diameter, patients with high hENT1 expression had significantly longer disease-free survival and overall survival (OS) than patients with low expression, whereas high hCNT3 expression was only associated with longer OS. In a combined analysis, patients with two favorable prognostic factors (hENT1 high / hCNT3 high expression) had a longer survival (median OS, 94.8 months) than those having one (median OS, 18.7 months) or no (median OS, 12.2 months) favorable prognostic factor. Conclusions: Pancreatic adenocarcinoma patients with a high expression of hENT1and hCNT3 immunostaining have a significantly longer survival after adjuvant gemcitabine-based chemoradiation. These biomarkers deserve prospective evaluation in patients receiving gemcitabinebased adjuvant therapy.Pancreatic head adenocarcinoma has a very poor prognosis.Even after curative surgery, which concerns only 10% to 15% of patients at the time of the diagnosis, 5-year survival is only 10% to 20% and median survival is 20 to 24 months (1, 2). This poor survival rate is attributed to a high rate of local recurrence and development of distant metastases even after complete resection of the tumor (R0 surgery). Several multimodal adjuvant and neoadjuvant therapies have been developed to reduce both local and systemic recurrence of the disease and improve survival. Nevertheless, the value of such adjuvant radiotherapy and/or chemotherapy regimens remains questionable because several trials have failed to draw any firm conclusions. Most of these adjuvant treatments were based on the combination of radiation and 5-fluorouracil (2 -5).Gemcitabine is a 2 ¶,2 ¶-difluoro-2-deoxycytidine analogue that inhibits DNA replication and repair. Gemcitabine monotherapy has clinically important activity in advanced and metastatic pancreatic adenocarcinoma and for which it is now the standard of care (6). In the adjuvant setting, it was enhanced disease-free survival (DFS) and survival compared with surgery alone (7, 8) and significantly increased DFS, but not overall survival (OS), when added to 5-fluorouracil-based chemoradiotherapy in a recent RTOG trial (9).As gemcitabine possesses radiosensitizing prope...

show abstract

Section: Discussionmentioning

confidence: 99%

“…Patients from two Belgian multicentric phase II studies evaluating the feasibility of adjuvant gemcitabine-based combined regimen in resected pancreatic cancer patients between 2000 and 2003 were studied (15,16). Both studies were approved by the ethics committees of each participating center.…”

Section: Methodsmentioning

confidence: 99%

Human Equilibrative Nucleoside Transporter 1 and Human Concentrative Nucleoside Transporter 3 Predict Survival after Adjuvant Gemcitabine Therapy in Resected Pancreatic Adenocarcinoma

Maréchal¹,

Mackey²,

Lai

et al. 2009

Clinical Cancer Research

Self Cite

199

159

View full text Add to dashboard Cite

show abstract

“…Several studies have investigated gemcitabine-based chemoradiotherapy regimens in resected pancreatic cancer (35), unresectable pancreatic cancer (36 -42), and lung and pleural malignancies (43)(44)(45)(46). With pancreatic malignancies, dose-limiting toxicities (DLTs) of gemcitabine-based chemoradiotherapy include cytopenias, anorexia, nausea, and vomiting, whereas with lung malignancies, DLTs include esophagitis, pneumonitis, and cytopenias.…”

Section: Introductionmentioning

confidence: 99%

Phase I Study of Concomitant Chemoradiotherapy with Paclitaxel, Fluorouracil, Gemcitabine, and Twice-Daily Radiation in Patients with Poor-Prognosis Cancer of the Head and Neck

Milano

Haraf

Stenson

et al. 2004

Clinical Cancer Research

View full text Add to dashboard Cite

Purpose: We previously demonstrated high locoregional control, in patients with poor-prognosis head and neck cancer (HNC), using paclitaxel, 5-fluorouracil, hydroxyurea, and concomitant hyperfractionated radiotherapy. In the present phase I trial, gemcitabine, a novel antimetabolite with strong radiation-enhancing activity, replaces hydroxyurea. We sought to determine the recommended phase II dose and clinical efficacy in poor-prognosis HNC patients.Experimental Design: Seventy-two patients enrolled. Eligibility criteria included recurrent or second primary HNC, metastases or expected 2-year survival <20%. Chemoradiotherapy consisted of 5-fluorouracil, 600 mg/m 2 /d, for 5 days; paclitaxel, 100 mg/m 2 on Day 1; and concurrent 1.5 Gy twice-daily radiation for 5 days. Gemcitabine was dose escalated, 50 -300 mg/m 2 on day 1. Cycles repeated every 14 days until the completion of chemoradiation. Dose-limiting toxicities (DLTs) included: neutropenic fever; grade >4 neutropenia or thrombocytopenia for >4 days; grade >4 mucositis or dermatitis for >7 days; or grade 3 toxicity necessitating chemotherapy dose reductions. Non-DLT dose reductions in 5-fluorouracil and/or paclitaxel were allowed.Results: Seventy-nine percent of assessable patients experienced a clinical response. Five-year actuarial survival is 33.0%, and locoregional control is 61.4%. The recommended phase II dose of gemcitabine in this regimen is 100 mg/m 2 during cycles 1-5 (1 of 7 patients with DLT) or 200 mg/m 2 delivered only during cycles 3-5 (3 of 19 with DLT). Grades 3 and 4 mucositis (56 and 21%, respectively) and dermatitis (25 and 21%, respectively) were common.Conclusions: Gemcitabine, 5-fluorouracil, paclitaxel, and twice-daily radiation, delivered on alternating weeks, is active in patients with poor-prognosis HNC, although severe mucositis limits the clinical applicability of this regimen. Refinements in radiotherapy, including intensity-modulated radiation therapy, may improve the tolerance for this regimen.

show abstract

“…While these are phase I data, the median survival was an acceptable 16.5 months. Van Laethem et al, in a feasibility study, found that gemcitabine (300 mg m À2 ) given weekly with split-course radiation (40 Gy/20 fractions over 6 weeks) was tolerable following three cycles of standard dose gemcitabine (1000 mg m À2 day 1 and 8 q 21 days) (Van Laethem et al, 2003). While limited to 22 patients, the median disease-free survival and overall survival was 6 and 15 months, respectively.…”

Section: Discussionmentioning

confidence: 99%

Adjuvant gemcitabine and concurrent radiation for patients with resected pancreatic cancer: a phase II study

et al. 2006

View full text Add to dashboard Cite

The safety and efficacy of gemcitabine and concurrent radiation to the upper abdomen followed by weekly gemcitabine in patients with resected pancreatic cancer was determined. Patients with resected adenocarcinoma of the pancreas were treated with intravenous gemcitabine administered twice-weekly (40 mg m À2) for 5 weeks concurrent with upper abdominal radiation (50.4 Gy in 5 1 2 weeks). At the completion of the chemoradiation, patients without disease progression were given gemcitabine (1000 mg m À2 ) weekly for two cycles. Each cycle consisted of 3 weeks of treatment followed by 1 week without treatment. Forty-seven patients were entered, 46 of whom are included in this analysis. Characteristics: median age 61 years (range 35 -79); 24 females (58%); 73% stage T3/T4; and 70% lymph node positive. Grade III/IV gastrointestinal or haematologic toxicities were infrequent. The median survival was 18.3 months, while the median time to disease recurrence was 10.3 months. Twenty-four percent of patients were alive at 3 years. Only six of 34 patients with progression experienced local regional relapse as a component of the first site of failure. These results confirm the feasibility of delivering adjuvant concurrent gemcitabine and radiation to the upper abdomen. This strategy produced good local regional tumour control. Cure with surgery alone for patients with operable pancreatic adenocarcinoma remains infrequent. A small randomised trial reported by the Gastrointestinal Study Group (GITSG) demonstrated an improvement in median and overall survival for patients treated with a surgical resection who were randomised to adjuvant 5-fluorouracil-based chemoradiation (vs observation) (1987). The chemoradiation consisted of bolus 5-fluorouracil (5-FU) and split course radiation to a total dose of 40 Gy. The median and 2-year survival for the surgery alone patients was 11 months and 18% vs 20 months and 43%, respectively, for the patients receiving adjuvant therapy. The European Organization for the Research and Treatment of Cancer (EORTC) attempted to replicate the results of the GITSG trial but failed to confirm a statistical benefit, despite a 4.5-month improvement in median survival for patients receiving adjuvant chemoradiation (Klinkenbijl et al, 1999). In an update of the European Study for Pancreatic Cancer (ESPAC 1) trial, six cycles of adjuvant 5-FU chemotherapy given alone or following split-course 5-FU-based chemoradiation appeared to provide a survival benefit over surgery alone (Neoptolemos et al, 2004). While the results of the ESPAC trial leave in question the role of radiation therapy in this setting, the use of chemoradiation reflects an accepted standard in the United States.Gemcitabine is active as a single agent in the treatment of pancreatic cancer (Casper et

show abstract

Postoperative adjuvant gemcitabine and concurrent radiation after curative resection of pancreatic head carcinoma: a phase II study

Cited by 48 publications

References 18 publications

Human Equilibrative Nucleoside Transporter 1 and Human Concentrative Nucleoside Transporter 3 Predict Survival after Adjuvant Gemcitabine Therapy in Resected Pancreatic Adenocarcinoma

Human Equilibrative Nucleoside Transporter 1 and Human Concentrative Nucleoside Transporter 3 Predict Survival after Adjuvant Gemcitabine Therapy in Resected Pancreatic Adenocarcinoma

Phase I Study of Concomitant Chemoradiotherapy with Paclitaxel, Fluorouracil, Gemcitabine, and Twice-Daily Radiation in Patients with Poor-Prognosis Cancer of the Head and Neck

Adjuvant gemcitabine and concurrent radiation for patients with resected pancreatic cancer: a phase II study

Contact Info

Product

Resources

About