6% alive at one year in the RT (+) group versus 37.5% in the RT (-) group (P=0.15). Median OS was 12.5 versus 9.1 months for the RT (+) group and RT (-) groups, respectively (Figure 2). Figure 1 Progression free survival (months) Figure 2 Overall survival (months) In patients
with good or excellent performance status (ECOG 0-1), subset analysis showed that PFS was 10.5 months compared to 7.6 months for the RT (+) and RT (-) groups, respectively (P=0.7574). The median OS was 12.2 months versus 7.6 months for the RT (+) groups and RT (-) groups, Inhibitors,research,lifescience,medical respectively (P=0.54) in the ECOG 0-1 subset. Discussion The role of combined therapy for LAPC continues to evolve. The goals of radiotherapy in LAPC include improvement in local control and palliation of pain and/or obstructive symptoms. Trials of chemoradiation versus chemotherapy alone in LAPC
have reported mixed findings regarding survival and are summarized in Table 4 (4-6,9,10). In a trial conducted by the Gastrointestinal Tumor Study Inhibitors,research,lifescience,medical Group (5), the effect of concurrent chemoradiotherapy versus chemotherapy alone in LAPC was evaluated and a benefit in survival from combined modality therapy Inhibitors,research,lifescience,medical was noted. The chemoradiation arm consisted of radiation combined with 5-fluorouracil to a total dose of 54 Gy in 1.8 Gy fractions followed by maintenance streptozocin, mitomycin and 5-fluorouracil (SMF). The chemotherapy-only arm was SMF combination chemotherapy for two years or until progression. In this trial, the one-year OS was 41% in the chemoradiation arm compared to 19% in the chemotherapy-alone arm (P<0.02). Table 4 Randomized trials comparing chemoradiation versus chemotherapy Modern chemotherapy and radiation techniques have been tested in two recent phase III trials evaluating the efficacy Inhibitors,research,lifescience,medical of chemoradiation. In the trial by the Eastern Cooperative Oncology Group (E4201), patients with LAPC were randomly assigned to chemoradiation (50.4 Gy in 28 fractions) with concurrent gemcitabine (600 mg/m2 ZD1839 molecular weight weekly ×6) followed by 5 cycles of gemcitabine alone (1,000 mg/m2 weekly ×3 every 4 wks) versus
Inhibitors,research,lifescience,medical gemcitabine alone (1,000 mg/m2 weekly ×3 every 4 wks) for 7 cycles. This trial showed that chemoradiation was associated with a slightly improved PAK6 survival (11 versus 9.2 months, P=0.044) (4). In a second recent study by Chauffert et al. reported in 2008 (10), chemoradiation was delivered to a total dose of 60 Gy concurrently with cisplatin (20 mg/m2/day, days 1-5 during weeks 1 and 5) and 5-fluorouracil (300 mg/m2/day, days 1-5 for 6 weeks). The chemotherapy-alone arm consisted of gemcitabine (1,000 mg/m2 weekly for 7 weeks). Maintenance gemcitabine (1,000 mg/m2 weekly, 3/4 weeks) was given in both arms until disease progression or toxicity. Overall survival in this trial was shorter in the chemoradiotherapy arm (13.0 vs. 8.6 months, P=0.044) and these patients experienced a higher rate of grade 3-4 toxicity compared with the chemotherapy arm (66% vs. 40% respectively; P=0.0008).