Gemcitabine-radiotherapy in patients with locally advanced pancreatic cancer

Department of Medical Oncology, University Hospital Vrije Universiteit, Amsterdam, The Netherlands.
European Journal of Cancer (Impact Factor: 5.42). 07/2002; 38(9):1212-7. DOI: 10.1016/S0959-8049(02)00076-X
Source: PubMed


A feasibility study was performed to assess the toxicity and efficacy of a combination of gemcitabine-radiotherapy in patients with locally advanced pancreatic cancer (LAPC). 24 patients (15 females and 9 males) with measurable LAPC were included; the median age of the patients was 63 years (range 39-74 years). The performance status ranged from 0 to 2. Gemcitabine was administered at a dose of 300 mg/m(2), concurrent with radiotherapy, three fractions of 8 Gy, on days 1, 8 and 15. When compliance allowed, gemcitabine alone was continued thereafter, at 1000 mg/m(2), weekly times 3, every 4 weeks, depending on the response and toxicity. All patients were evaluable for toxicity and response. The objective response rate was 29.2% (1 complete remission+6 partial remissions); 12 patients had stable disease. However, 2 of the radiological partial remissions were shown to be complete remissions by pathology assessment. Median duration of response was 3 months (range 1-35+months). Median time to progression was 7 months (range 2-37+months). Median survival was 10 months (range 3-37+months). Dose reduction or omission of gemcitabine was necessary in 10 patients. Non-haematological toxicity consisted of 87.5% nausea and vomiting grade I-II, diarrhoea 54%, ulceration in stomach and duodenum 37.5% (20.8% ulceration with bleeding); 1 patient developed a fistula between the duodenum and aorta, 5 months after treatment. Anaemia grade III-IV was observed in 8.3% of the patients. Neutropenia grade III-IV was observed in 8.3%, thrombocytopenia grades III-IV in 16.7%. In 1 patient who underwent resection postchemoradiation, no viable tumour cells were found. In addition, in the patient who suddenly died of a fistula between the duodenum and aorta, no viable tumour cells were detectable at autopsy. Although the toxicity of this treatment was occasionally severe, the response and survival are encouraging and warrant further studies of this combination.

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    • "In this series of 24 patients, the authors report a 37.5% incidence of ulceration in the stomach (9 patients) with 5 of these having associated bleeding. Two deaths were reported, including one from a bleeding ulcer and another from the development of an aortoduodenal fistula [35]. "
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    • "The benefit seen in the early combinedmodality trials was modest, however, with a median survival of only 10 months. To improve the efficacy of the treatment, various anticancer agents such as gemcitabine and radiation schedules are being examined in clinical trials (Burris et al, 1997; Blackstock et al, 1999; McGinn et al, 2001; de Lange et al, 2002; McGinn and Zalupski, 2003; Okusaka et al, 2004). As yet, however, no regimen has been shown to be superior to conventional chemoradiotherapy with 5-FU. "
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