Subject to prospective validation, gemcitabine should not be used for patients with low tumor hENT1 expression.

PKC412 can be safely administered by chronic oral therapy, and 150 mg/d is suitable for phase II studies. The pharmacokinetics and lack of conventional toxicity indicate that pharmacodynamic measures may be additionally needed to optimize the drug dose and schedule.

R1-direct resections were associated with significantly reduced overall and recurrence-free survival following pancreatic cancer resection. Resection margin involvement was also associated with an increased risk for local recurrence.

In addition to postoperative R-status, an elevated NLR is also a valuable prognostic marker in patients undergoing chemoradiation for locally advanced rectal carcinoma. It is associated with worse OS, TTLR and DFS. An elevated NLR may be a useful additional tool in guiding the decision-making process for adjuvant or neoadjuvant therapies.

No abstract

The presence of a systemic inflammatory response, as evidenced by the GPS, appears to be superior to the subjective assessment of performance status (ECOG-ps) in predicting the response to platinum-based chemotherapy in patients with advanced gastroesophageal cancer.

Background:SCALOP, a randomised, phase II trial, tested the activity and safety of gemcitabine (GEM)-based and capecitabine (CAP)-based chemoradiation (CRT) for locally advanced pancreatic cancer (LAPC). Here we present the long-term outcomes.Methods:Eligibility: histologically proven LAPC ⩽7 cm. Following 12 weeks of induction GEMCAP chemotherapy (three cycles: GEM 1000 mg m−2 days 1, 8, 15; CAP 830 mg m−2 days 1–21 q28 days) patients with stable/responding disease, tumour ⩽6 cm, and WHO Performance Status 0–1 were randomised to receive one cycle GEMCAP followed by CAP (830 mg m−2 b.d. on weekdays only) or GEM (300 mg m−2 weekly) with radiation (50.4 Gy per 28 fractions).Results:One-hundred fourteen patients (28 UK centres) were registered between 24 December 2009 and 25 October 2011, and 74 were randomised (CAP-RT=36; GEM-RT=38). At the time of this analysis, 105 of the 114 patients had died and the surviving 9 patients had been followed up for a median of 10.9 months (IQR: 2.9–18.7). Updated median OS was 17.6 months (95% CI: 14.6–22.7) in the CAP-CRT arm and 14.6 months (95% CI: 11.1–16.0) in the GEM-CRT arm (intention-to-treat adjusted hazard ratio (HR): 0.68 (95% CI: 0.38–1.21, P=0.185)); median progression-free survival (PFS) was 12.0 months (95% CI: 10.0–15.2) in the CAP-CRT arm and 10.4 months (95% CI: 8.8–12.7) in the GEM-CRT arm (intention-to-treat adjusted HR: 0.60 (95% CI: 0.32–1.14, P=0.120)). In baseline multivariable model, age ⩾65 years, better performance status, CA19.9<613 IU l−1, and shorter tumour diameter predicted improved OS. CAP-CRT, age ⩾65 years, better performance status, CA19.9 <46 IU ml−1 predicted improved OS and PFS in the pre-radiotherapy model. Nine-month PFS was highly predictive of OS.Conclusions:CAP-CRT remains the superior regimen. SCALOP showed that patients with CA19.9 <46 IU ml−1 after induction chemotherapy are more likely to benefit from CRT.

Summary We have previously shown that loss of p53 function in A2780 human ovarian adenocarcinoma cells confers increased clonogenic resistance to several DNA-damaging agents, but not to taxol or camptothecin. We have now extended these studies, comparing wild-type p53-expressing A2780 cells with isogenic derivatives transfected with a dominant negative mutant (143; val to ala) p53. We show that, as well as retaining equivalent clonogenic sensitivity to camptothecin, mutant p53 transfectants of A2780 cells do not acquire significantly increased resistance to the camptothecin analogues topotecan and SN-38, the active metabolite of CPT-11. Compared with vector-alone transfectants they are, however, relatively (2.2-fold) resistant to GI 147211, a further camptothecin analogue undergoing clinical trial. Treatment of A2780 with camptothecin and each analogue produces an increase, maximal at 24-48 h after drug exposure, of cells in the G/M phase of the cell cycle and a decrease in both G, and S-phase cells. The G2 arrest is independent of p53 function for camptothecin and the three analogues. All four compounds can induce apoptosis in A2780, which is reduced in mutant p53 transfectants, as measured using the terminal DNA transferase-mediated b-d UTP nick end labelling (TUNEL) assay. Thus, although p53-dependent apoptosis is induced by camptothecin, topotecan and SN-38 in this human ovarian carcinoma cell line, these drugs induce p53-independent death, as measured by clonogenic assay.