Medline ® Abstracts for References 32,39-41
Adjuvant gemcitabine alone versus gemcitabine-based chemoradiotherapy after curative resection for pancreatic cancer: a randomized EORTC-40013-22012/FFCD-9203/GERCOR phase II study.
Van Laethem JL, Hammel P, Mornex F, Azria D, Van Tienhoven G, Vergauwe P, Peeters M, Polus M, Praet M, Mauer M, Collette L, Budach V, Lutz M, Van Cutsem E, Haustermans K
J Clin Oncol. 2010;28(29):4450. Epub 2010 Sep 13.
PURPOSE: The role of adjuvant chemoradiotherapy (CRT) in resectable pancreatic cancer is still debated. This randomized phase II intergroup study explores the feasibility and tolerability of a gemcitabine-based CRT regimen after R0 resection of pancreatic head cancer.
PATIENTS AND METHODS: Within 8 weeks after surgery, patients were randomly assigned to receive either four cycles of gemcitabine (control arm) or gemcitabine for two cycles followed by weekly gemcitabine with concurrent radiation (50.4 Gy; CRT arm). The primary objective was to exclude a<60% treatment completion and a>40% rate of grade 4 hematologic or GI toxicity in the CRT arm with type I and II errors of 10%. Secondary end points were late toxicity, disease-free survival (DFS), and overall survival (OS).
RESULTS: Between September 2004 and January 2007, 90 patients were randomly assigned (45:45). Patient characteristics were similar in both arms. Treatment was completed per protocol by 86.7% and 73.3% (80% CI, 63.1% to 81.9%; 95% CI, 58.1% to 85.4%) in the control and CRT arms, respectively, and grade 4 toxicity was 0% and 4.7% (two of 43; 80% CI, 1.2% to 11.9%), respectively. In the CRT arm, three patients experienced grade 3-related late toxicity. Median DFS was 12 months in the CRT arm and 11 months in the control arm. Median OS was 24 months in both arms. First local recurrence was less frequent in the CRT arm (11% v 24%).
CONCLUSION: Adjuvant gemcitabine-based CRT is feasible, well-tolerated, and not deleterious; adding this treatment to full-dose adjuvant gemcitabine after resection of pancreatic cancer should be evaluated in a phase III trial.
Department of Gastroenterology, Erasme University Hospital, UniversitéLibre de Bruxelles, Brussels, Belgium. JL.Vanlaethem@erasme.ulb.ac.be
Adjuvant gemcitabine and concurrent continuous radiation (45 Gy) for resected pancreatic head carcinoma: a multicenter Belgian Phase II study.
Demols A, Peeters M, Polus M, HonoréP, Boterberg T, Gay F, Closon MT, Van Houtte P, Closset J, Van Laethem JL
Int J Radiat Oncol Biol Phys. 2005;62(5):1351.
PURPOSE: To evaluate the feasibility and tolerance of a postoperative course of gemcitabine (GEM) combined with continuous radiation after curative resection of pancreatic adenocarcinoma.
METHODS AND MATERIALS: Thirty patients (median age, 61 years; performance status, 0 to 1) with Stage II and III curatively resected pancreatic head adenocarcinoma were included. Gemcitabine 1000 mg/m2 (3 out of 4 weeks, two cycles) was given within 8 weeks of surgery and followed by GEM 300 mg/m2 weekly combined with continuous radiation (45 Gy in 25 fractions, 1.8 Gy per fraction).
RESULTS: For GEM alone, all patients received the two courses with dose reductions in 14 of 30 patients (46%). All but 3 patients completed full chemoradiation; 1 stopped radiation because of subocclusion of a gastroenterostomy, and 2 did not start owing to disease progression. Reduction in GEM during radiation was necessary in 12 of 30 patients (40%). No toxic death was noted; World Health Organization Grade 3/4 hematologic and nonhematologic toxicities were seen in 10 of 30 patients (33%) and 3 of 30 patients (10%), respectively. After a median follow-up of 19 months, no late toxicity was reported. Eleven patients died from progressive disease; median disease-free survival and overall survival were 14.5 and 19 months, respectively.
CONCLUSION: This adjuvant combination is well tolerated and can be safely administered after curative surgery for pancreatic cancer. Further evaluation of this regimen is ongoing.
Medico-surgical Department of Gastroenterology, Erasme University Hospital, Brussels, Belgium. email@example.com
Concurrent chemoradiotherapy with gemcitabine and cisplatin after incomplete (R1) resection of locally advanced pancreatic carcinoma.
Wilkowski R, Thoma M, Dühmke E, Rau HG, Heinemann V
Int J Radiat Oncol Biol Phys. 2004;58(3):768.
PURPOSE: To analyze, in a prospective clinical trial, the efficacy and toxicity of concurrent radiotherapy and chemotherapy with gemcitabine and cisplatin in patients with incompletely (R1) resected pancreatic cancer.
METHODS AND MATERIALS: Between 2000 and 2002, a total of 30 pancreatic cancer patients were treated. Radiotherapy was performed in 15 patients up to a total dose of 45.0 Gy. An additional 15 patients received a total dose of 50.0 Gy according to the International Commission on Radiation Units and Measurements (ICRU) Report 50 reference point (equivalent to 45.0 Gy at the isodose, including 90% covering the former tumor area and local lymph nodes). Concurrent with radiotherapy, four applications of gemcitabine (300 mg/m(2)) and cisplatin (30 mg/m(2)) were administered. After chemoradiotherapy, patients received four additional courses of gemcitabine (1000 mg/m(2)) and cisplatin (50 mg/m(2)) on Days 1 and 15 in a 4-week cycle.
RESULTS: The median progression-free survival was 10.6 months, and the median overall survival was 22.8 months. The 1-, 2-, and 3-year survival rate was 81%, 43%, and 26%, respectively. After completion of chemoradiotherapy, distant metastasis was observed in 14 patients during a median follow-up of 15.0 months (range, 4.6-30.0). One patient developed both local recurrence and distant metastases. Hematologic toxicities were the most prominent side effects (leukopenia Grade 3 and 4 in 53% and 7% and thrombocytopenia Grade 3 and 4 in 33% and 7% of patients, respectively). Grade 3 and 4 GI toxicity was not observed.
CONCLUSION: Postoperative chemoradiotherapy with gemcitabine and cisplatin after incomplete (R1) resection of pancreatic carcinoma is safe and feasible. A prolonged progression-free survival suggests high local efficacy, translating into a benefit of overall survival. On the basis of the favorable outcome of patients receiving gemcitabine/cisplatin-based chemoradiotherapy, testing this combined treatment strategy appears warranted in a comparative trial.
Klinik und Poliklinik für Strahlentherapie und Radioonkologie, Universität München, München, Germany. firstname.lastname@example.org
Adjuvant gemcitabine and concurrent radiation for patients with resected pancreatic cancer: a phase II study.
Blackstock AW, Mornex F, Partensky C, Descos L, Case LD, Melin SA, Levine EA, Mishra G, Limentani SA, Kachnic LA, Tepper JE
Br J Cancer. 2006;95(3):260. Epub 2006 Jul 25.
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(-2)) 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(-2)) 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.
Department of Radiation Oncology, Wake Forest University School of Medicine, Medical Center Blvd, Winston-Salem, NC 27157, USA. email@example.com