Phase II study of radiotherapy combined with gemcitabine for locally advanced pancreatic cancer

Abstract

Gemcitabine has been reported to be a potent radiosensitiser in human pancreatic cell lines. This study was conducted to evaluate the efficacy and toxicity of radiotherapy combined with gemcitabine for locally advanced pancreatic cancer. In all, 42 patients with pancreatic cancer that was unresectable but confined to the pancreatic region were treated with external-beam radiation (50.4 Gy in 28 fractions over 5.5 weeks) and weekly gemcitabine (250 mg m À2 , 30-min infusion). Maintenance gemcitabine (1000 mg m À2 weekly  3 every 4 weeks) was initiated 1 month after the completion of the chemoradiotherapy and continued until disease progression or unacceptable toxicity. Of the 42 patients, 38 (90%) completed the scheduled course of chemoradiotherapy. The major toxicity was leucopenia and anorexia. There was one death attributed to duodenal bleeding and sepsis. The median survival time was 9.5 months and the 1-year survival rate was 28%. The median progression-free survival time was 4.4 months. In 35 patients with documented disease progression at the time of analysis, 34 (97%) showed distant metastasis as the cause of the initial disease progression. The chemoradiotherapy used in this study has a moderate activity against locally advanced pancreatic cancer and an acceptable toxicity profile. Future investigations for treatment with more systemic effects are warranted.

Weekly full-dose gemcitabine and single-dose cisplatin with concurrent radiotherapy in patients with locally advanced pancreatic cancer

“…We summarised recent phase II trials on chemoradiotherapy combined with gemcitabine alone or gemcitabine plus cisplatin in locally advanced pancreatic cancer (Table 4) (de Lange et al, 2002;Li et al, 2003;Okusaka et al, 2004;Wilkowski et al, 2004;Magnino et al, 2005;Haddock et al, 2007). Compared with the recent phase II study by Haddock et al, although the dose and cycle differed from our study, 24.4% ORR and 16.7 months median survival time of our study showed favourable results.…”

“…On the basis of the most conservative assumption of a 30% survival rate at 1 year (null hypothesis) in historic controls with locally advanced pancreatic cancer (Okusaka et al, 2004), an increase of 50% or more (alternative hypothesis) could be shown with a power of 80% by investigating a sample size of at least 35 patients (a ¼ 0.05, one-sided test) (A'Hern, 2001). Overall survival and TTP were analysed using Kaplan -Meier method with 95% confidence intervals (CIs).…”

“…Although we found no consensus between administration schedules for gemcitabine with radiation, recent studies have used twice weekly or weekly administrations of gemcitabine for their main therapeutic schedules (Blackstock et al, 1999;McGinn et al, 2001;Okusaka et al, 2004;Magnino et al, 2005). According to the fact that patients with resectable pancreatic cancer developed early recurrence after surgery due to micrometastases and distant early metastases were important cause of treatment failure of chemoradiotherapy in patients with locally advanced pancreatic cancer, we used weekly gemcitabine treatments in our study (Yeo et al, 1997;Paulino and Latona, 2000).…”

“…Previous phases I and II studies were performed with radiotherapy doses of 42 -50.4 Gy and sometimes used boosting doses to achieve local control (Blackstock et al, 1999;McGinn et al, 2001;Brunner et al, 2003;Okusaka et al, 2004;Magnino et al, 2005). In the present study, we used radiation doses of 45 Gy with 25 fractions.…”

“…Since 1996, gemcitabine, a pyrimidine analogue and potent radiosensitiser, has been studied as a substitute for 5-FU in treatments using concurrent chemoradiotherapy (Blackstock et al, 1999;McGinn et al, 2001). Recent phases I and II studies on gemcitabine-based chemoradiotherapy were feasible and improved therapeutic response and survival (Blackstock et al, 1999;McGinn et al, 2001;Okusaka et al, 2004;Magnino et al, 2005).…”