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Pemetrexed/gemcitabine versus gemcitabine in pancreatic cancer
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Pancreatic cancer accounts for more than 200 000 deaths worldwide each year, with most patients presenting with unresectable, locally advanced or metastatic disease. In multiple phase III studies in patients with pancreatic cancer, single-agent gemcitabine has shown response rates of 5.426%, median survival of approximately 6 months and 1-year survival of approximately 20%. Pemetrexed, a multitargeted antifolate, has demonstrated single-agent activity in pancreatic cancer with a response rate of 5.7%, median survival of 6.5 months, and 1-year survival of 28%, reported in a phase II study. In this issue, Oettle et al. report the results of a phase III study that aimed to compare the efficacy, in terms of overall survival (OS), of pemetrexed plus gemcitabine versus standard gemcitabine in patients with advanced pancreatic cancer. These authors report that pemetrexed plus gemcitabine did not improve OS, and they conclude that single-agent gemcitabine remains the standard of care for advanced pancreatic cancer.
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Single-agent rituximab for follicular or mantle cell lymphoma
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Although in some patients with follicular (FL) and mantle cell (MCL) lymphoma aggressive interventions such as autologous or allogeneic transplantation may prolong survival or eventually lead to cure, these diseases are usually considered incurable. In this predominantly palliative setting, the optimal treatment may be one producing the least side-effects while obtaining a long period of time without symptoms of disease. Single-agent rituximab is one such option, showing little toxicity and obtaining, given at a prolonged schedule and in some patient subsets, remissions that are comparable to those obtained with multi-agent regimens. Nevertheless, many physicians are reluctant to apply single-agent immunotherapy, fearing an insufficient activity compared with more traditional schemes. In this issue Ghielmini et al. present an analysis of a number of characteristics of 306 patients with FL or MCL and of their disease that could predict benefit from treatment with single-agent rituximab, and describe the observed short- and long-term major side-effects.
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Lung cancer mortality in European women
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Lung cancer mortality in men has been declining since the late 1980s in most European countries. In women, although rates are still appreciably lower than those for men, steady upward trends have been observed in most countries. In this issue Bosetti et al. present a study that examined lung cancer trends in women over the last four decades in 33 European countries (including the 25 EU states as of May 2004) to provide world aged-standardized rates per 100 000 at all ages and for two (overlapping) age groups: 2044 and 3564 years. These authors report that in the 25 EU countries mortality rose by over one-fifth (23.8%) between the early 1980s and the early 1990s, up from 7.8 to 9.6 per 100 000. From the early 1990s it rose by a further 16% to reach 11.2 per 100 000 in the year 20002001. Only six European countriesEngland, Wales, Latvia, Lithuania, Russia and Ukraineshowed a fall over the last decade, although in several countries the upward trend was slowing.
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Imatinib and hydroxyurea in glioblastoma multiforme
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Glioblastoma multiforme (GBM), though relatively rare, occurring at a rate of seven per 100 000 tumors, is common among brain tumors. A summary of eight phase II trials with cytotoxic or cytostatic drugs for treatment of recurrent GBM at a single center showed a 6-month progression-free survival rate of 15% and a median OS rate of 30 weeks. Preliminary trials with imatinib, an inhibitor of platelet-derived growth factor receptors
and ß, as well as other selected tyrosine kinases, as monotherapy for treatment of GBM have suggested limited efficacy. Preclinical studies, however, suggest that imatinib increases the chemosensitivity of glioblastoma cells, so enhancing the activity of other chemotherapeutic agents used to treat GBM. In this issue, Dresemann reports the results of a patient series in which the combination of imatinib and hydroxyurea was investigated in patients with progressive temozolomide-resistant GBM. In this series the combination therapy resulted in a 20% response rate, including complete and partial responses. Moreover, the combination was well tolerated, and Dresemann suggests that it shows promise as therapy for GBM.
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Quote
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"It's horrible," said Bobbie. "Oh, I wish Dr Forrest would make haste. Oh, poor Jim!"
"It IS horrible," said Peter, "but it's very exciting. I wish Doctors weren't so stuck-up about who they'll have in the room when they're doing things. I should most awfully like to see a leg set. I believe the bones crunch like anything."
Dr Forrest makes a house call in E. Nesbitt's The Railway Children.