- Email: [email protected]
Chemoradiotherapy for management of pancreatic cancer
News
EGF and risk of hepatocellular carcinoma polymorphisms and EGF expression in HCC cell lines and human liver tissue. They then studied the association between EGF polymorphisms and HCC in patients with cirrhosis in two case– control studies (a US study [n=207] and a French validation study [n=121]). EGF secretion was 2·3–times higher in G/G cell lines than in A/A cell lines, the researchers noted. In the US study, compared with the A/A genotype, patients with the A/G genotype had an odds ratio (OR) of 2·4 (95% CI 1–5·4; p=0·05) for development of HCC, and for those with the G/G genotype the OR was 4·0 (1·6–9·6; p=0·002). Number of copies of G was significantly associated with HCC, after adjusting for various factors (hazard ratio for G/G plus A/G vs A/A 3·49 [1·29–9·44; p=0·01]). “The results strongly suggest the importance of inhibiting the EGF/ EGFR axis as a therapeutic strategy for HCC patients,” comments Camillo
Porta (IRCCS San Matteo University Hospital Foundation, Pavia, Italy). This study hints at the opportunity to select patients more appropriately for EGFR antagonists, adds Ulrich Lehmann (Hannover Medical School, Hannover, Germany).
Sanjit Bagchi
Dr E Walker/Science Photo Library
Functional polymorphism of the epidermal growth factor (EGF) gene increases risk of hepatocellular carcinoma (HCC) in patients with cirrhosis by increasing serum and liver EGF concentrations (JAMA 2008; 299: 53–60). Previous studies have shown that EGF polymorphisms modulate EGF concentrations and, in mouse models, over-expression of EGF has led to development of HCC. “EGF and the EGFR (EGF receptor) pathway appear to be excellent targets for chemoprevention in patients with cirrhosis”, says the study’s lead author Kenneth Tanabe (Massachusetts General Hospital, Boston, MA, USA). “Measurement of EGF [concentration] and EGF single nucleotide polymorphism is relevant in patients with cirrhosis to assess their risk for HCC and potentially modulate intensity of screening.” The researchers studied molecular mechanisms that linked 61*G allele
Study hints at new treatment strategies for hepatocellular carcinoma
Chemoradiotherapy for management of pancreatic cancer 3-dimensional (3D) radiotherapy can be safely administered between two courses of systemic gemcitabine chemotherapy for the management of pancreatic cancer (Int J Radiat Oncol Biol Phys, published online Dec 28, 2008; DOI: 10.1016/j.ijrobp.2007.08.070). Pancreatic cancer is one of the most difficult neoplasms to treat, with a 5-year survival of less than 5%. The prognosis is poor even in early disease and trials in these patients have shown that complex regimens yield little gain over single-agent chemotherapy. Nigel Spry (Sir Charles Gairdner Hospital, Perth, WA, Australia) and colleagues did a phase II study with two groups of patients, those with locally advanced, inoperable but non-metastatic disease, and those with resected cancer at high risk of local relapse. The 22 recruited postsurgery patients were required to have surgically defined risk factors for local http://oncology.thelancet.com Vol 9 February 2008
recurrence, but no metastatic disease. They received one 4-week cycle of gemcitabine, followed by 5–6 weeks of 3D conformal radiotherapy (CRT) with a continuous infusion of fluorouracil, 4 weeks of rest, and finally a further three cycles of gemcitabine. The median survival time of 15·6 months post-surgery compares well with chemotherapy-only regimens in similar patients, although the statistical power of the study was restricted by the small number of patients. No substantial postradiotherapy kidney or liver toxicity was noted. Inadvertent radiation damage to these organs is known to be a significant risk with radiotherapy for pancreatic cancer. Tom Crosby (Velindre Cancer Centre, Cardiff, UK) concludes that “this therapy can be delivered safely when given according to a detailed protocol with an appropriate quality assurance programme”.
However, grade 3 or 4 neutropenia was reported by 45·5% of post-surgery patients, and many needed a decrease in gemcitabine dose after radiotherapy. This worries Pippa Corrie (Addenbrooke’s Hospital, Cambridge, UK). “The neutropenia described here is well above what one would normally expect. Thus, 3D radiotherapy could be having a significant effect on bone marrow.” The study authors, while recommending that this regimen be tested further, conclude that radiotherapy might be best scheduled after chemotherapy. Somnath Mukherjee (Velindre Cancer Centre, Cardiff, UK) concurs: “patients do not tolerate chemotherapy after CRT, so consolidative radiotherapy should probably follow a prolonged chemotherapy course”.
Clare Sansom 101
EGF and risk of hepatocellular carcinoma polymorphisms and EGF expression in HCC cell lines and human liver tissue. They then studied the association between EGF polymorphisms and HCC in patients with cirrhosis in two case– control studies (a US study [n=207] and a French validation study [n=121]). EGF secretion was 2·3–times higher in G/G cell lines than in A/A cell lines, the researchers noted. In the US study, compared with the A/A genotype, patients with the A/G genotype had an odds ratio (OR) of 2·4 (95% CI 1–5·4; p=0·05) for development of HCC, and for those with the G/G genotype the OR was 4·0 (1·6–9·6; p=0·002). Number of copies of G was significantly associated with HCC, after adjusting for various factors (hazard ratio for G/G plus A/G vs A/A 3·49 [1·29–9·44; p=0·01]). “The results strongly suggest the importance of inhibiting the EGF/ EGFR axis as a therapeutic strategy for HCC patients,” comments Camillo
Porta (IRCCS San Matteo University Hospital Foundation, Pavia, Italy). This study hints at the opportunity to select patients more appropriately for EGFR antagonists, adds Ulrich Lehmann (Hannover Medical School, Hannover, Germany).
Sanjit Bagchi
Dr E Walker/Science Photo Library
Functional polymorphism of the epidermal growth factor (EGF) gene increases risk of hepatocellular carcinoma (HCC) in patients with cirrhosis by increasing serum and liver EGF concentrations (JAMA 2008; 299: 53–60). Previous studies have shown that EGF polymorphisms modulate EGF concentrations and, in mouse models, over-expression of EGF has led to development of HCC. “EGF and the EGFR (EGF receptor) pathway appear to be excellent targets for chemoprevention in patients with cirrhosis”, says the study’s lead author Kenneth Tanabe (Massachusetts General Hospital, Boston, MA, USA). “Measurement of EGF [concentration] and EGF single nucleotide polymorphism is relevant in patients with cirrhosis to assess their risk for HCC and potentially modulate intensity of screening.” The researchers studied molecular mechanisms that linked 61*G allele
Study hints at new treatment strategies for hepatocellular carcinoma
Chemoradiotherapy for management of pancreatic cancer 3-dimensional (3D) radiotherapy can be safely administered between two courses of systemic gemcitabine chemotherapy for the management of pancreatic cancer (Int J Radiat Oncol Biol Phys, published online Dec 28, 2008; DOI: 10.1016/j.ijrobp.2007.08.070). Pancreatic cancer is one of the most difficult neoplasms to treat, with a 5-year survival of less than 5%. The prognosis is poor even in early disease and trials in these patients have shown that complex regimens yield little gain over single-agent chemotherapy. Nigel Spry (Sir Charles Gairdner Hospital, Perth, WA, Australia) and colleagues did a phase II study with two groups of patients, those with locally advanced, inoperable but non-metastatic disease, and those with resected cancer at high risk of local relapse. The 22 recruited postsurgery patients were required to have surgically defined risk factors for local http://oncology.thelancet.com Vol 9 February 2008
recurrence, but no metastatic disease. They received one 4-week cycle of gemcitabine, followed by 5–6 weeks of 3D conformal radiotherapy (CRT) with a continuous infusion of fluorouracil, 4 weeks of rest, and finally a further three cycles of gemcitabine. The median survival time of 15·6 months post-surgery compares well with chemotherapy-only regimens in similar patients, although the statistical power of the study was restricted by the small number of patients. No substantial postradiotherapy kidney or liver toxicity was noted. Inadvertent radiation damage to these organs is known to be a significant risk with radiotherapy for pancreatic cancer. Tom Crosby (Velindre Cancer Centre, Cardiff, UK) concludes that “this therapy can be delivered safely when given according to a detailed protocol with an appropriate quality assurance programme”.
However, grade 3 or 4 neutropenia was reported by 45·5% of post-surgery patients, and many needed a decrease in gemcitabine dose after radiotherapy. This worries Pippa Corrie (Addenbrooke’s Hospital, Cambridge, UK). “The neutropenia described here is well above what one would normally expect. Thus, 3D radiotherapy could be having a significant effect on bone marrow.” The study authors, while recommending that this regimen be tested further, conclude that radiotherapy might be best scheduled after chemotherapy. Somnath Mukherjee (Velindre Cancer Centre, Cardiff, UK) concurs: “patients do not tolerate chemotherapy after CRT, so consolidative radiotherapy should probably follow a prolonged chemotherapy course”.
Clare Sansom 101