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TAS-102 for metastatic refractory colorectal cancer
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A new drug for metastatic colorectal cancer has efficacy in patients for whom other treatments have failed, according to a new study. The drug, TAS-102, is a combination of the nucleoside analogue trifluridine and tipiracil hydrochloride, a thymidine phosphorylase inhibitor. It was compared with placebo in a randomised trial of 800 patients with colorectal cancer from Australia, Europe, Japan, and the USA who had received at least two other treatments previously. In fact, most participants had received more than four previous treatments, including targeted drugs. After lung cancer, colorectal cancer causes more years-of-life-lost than any other cancer, and the outlook for patients with metastatic refractory disease is poor. “These are patients who have been heavily pretreated with all the available cytotoxics”, said Eric Van Cutsem (University Hospitals
Leuven, Leuven, Belgium), one of the study investigators. “The prognosis of these patients is very bad and… there is high unmet need for newer treatments.” Indeed, median survival was short: 5·3 months with placebo versus 7·1 months with TAS-102. As a result, Bernard Nordlinger (Assistance Publique Hôpitaux de Paris, Paris, France) was cautious about the immediate applicability of the findings: “I don’t think there’s a lot of logic to use drugs for 2 months of prolongation of survival”. Even so, clinicians might prefer TAS-102 to regorafenib, which is also used in this setting: TAS-102’s efficacy was similar to regorafenib and safety was better. “The drug was not very toxic, which is important in this situation”, said Van Cutsem. Grade 3 or higher events occurred in 69% of patients in the TAS-102 group
versus 52% in the placebo group, with neutropenia the most common event. Nordlinger added: “These are patients who have progressed with heavy chemoregimens and still there is a survival gain, not much—2 months— but the price to pay is low. There is very good safety.” Although the change in median survival was small, the risk of death was significantly lower with TAS-102 than with placebo (hazard ratio 0·68, 95% CI 0·58–0·81; p<0·001), which suggests that the drug might be useful when used in conjuction with other drugs or in different settings. Van Cutsem and colleagues plan to test the drug for earlier stage colorectal cancer and in combination with other active treatments, as well as in other gastrointestinal cancers.
Steve Gschmeissner/Science Photo Library
TAS-102 for metastatic refractory colorectal cancer
Published Online May 22, 2015 http://dx.doi.org/10.1016/ S1470-2045(15)70246-9 For the study by Mayer and colleagues see N Engl J Med 2015; 372: 1909–19
Sean Cleghorn
Androgen deprivation therapy and cognitive impairment? In patients with prostate cancer, androgen deprivation therapy (ADT) might lead to impaired cognitive performance within 6 months of starting treatment, according to a new study. Brian Gonzalez (Moffitt Cancer Center, FL, USA) and colleagues noted that ADT is not only associated with adverse effects (eg, fatigue and depressive symptoms) that interfere with cognitive functioning, but might also directly affect cognitive functioning by lowering testosterone levels. The study included 142 patients with prostate cancer (58 received ADT and 84 underwent only prostatectomy) and 88 agematched and education-matched men without prostate cancer. The researchers assessed how ADT affects cognitive performance, and identified demographic and genetic predictors of impaired cognitive functioning. www.thelancet.com/oncology Vol 16 July 2015
Gonzalez and colleagues showed that, in accordance with the International Cognition and Cancer Task Force criteria, patients with prostate cancer receiving ADT were more likely to show impaired cognitive performance than those in the control group within 6 months (OR 1·71, 95% CI 1·01–2·89) and 12 months (2·42, 1·27–4·61) of treatment commencement. Compared with all controls, recipients of ADT showed increased cognitive impairment over time (p=0·01). According to the researchers, the effects of ADT on impaired cognitive functioning were not moderated by age, baseline cognitive reserve, fatigue, depression, or hot flash interference (p≥0·09 for all comparisons). In the recipients of ADT, increased cognitive impairment over time was associated with a singlenucleotide polymorphism (rs1047776) of the GNB3 gene.
“Given these findings, oncologists may consider discussing cognitive impairment as a possible side-effect of ADT for prostate cancer patients”, commented Gonzalez. He added, “inquiring about cognitive functioning in patients receiving ADT could lead to early diagnosis and treatment for cognitive impairment that may result from ADT”. According to Michael Diefenbach (North Shore-Long Island Jewish Health System, Manhasset, NY, USA), this study is important, carefully undertaken, and should give patients clarity about the possible effect of ADT on their cognitive functioning. “Executive functioning appears to be most affected by ADT, and thus strategies to bolster such functioning need to be developed and evaluated”, he said.
Published Online May 22, 2015 http://dx.doi.org/10.1016/ S1470-2045(15)70247-0 For the study by Gonzalez and colleagues see J Clin Oncol 2015; published online May 11. DOI:10.1200/JCO.2014.60.1963
Sanjeet Bagcchi e314
A new drug for metastatic colorectal cancer has efficacy in patients for whom other treatments have failed, according to a new study. The drug, TAS-102, is a combination of the nucleoside analogue trifluridine and tipiracil hydrochloride, a thymidine phosphorylase inhibitor. It was compared with placebo in a randomised trial of 800 patients with colorectal cancer from Australia, Europe, Japan, and the USA who had received at least two other treatments previously. In fact, most participants had received more than four previous treatments, including targeted drugs. After lung cancer, colorectal cancer causes more years-of-life-lost than any other cancer, and the outlook for patients with metastatic refractory disease is poor. “These are patients who have been heavily pretreated with all the available cytotoxics”, said Eric Van Cutsem (University Hospitals
Leuven, Leuven, Belgium), one of the study investigators. “The prognosis of these patients is very bad and… there is high unmet need for newer treatments.” Indeed, median survival was short: 5·3 months with placebo versus 7·1 months with TAS-102. As a result, Bernard Nordlinger (Assistance Publique Hôpitaux de Paris, Paris, France) was cautious about the immediate applicability of the findings: “I don’t think there’s a lot of logic to use drugs for 2 months of prolongation of survival”. Even so, clinicians might prefer TAS-102 to regorafenib, which is also used in this setting: TAS-102’s efficacy was similar to regorafenib and safety was better. “The drug was not very toxic, which is important in this situation”, said Van Cutsem. Grade 3 or higher events occurred in 69% of patients in the TAS-102 group
versus 52% in the placebo group, with neutropenia the most common event. Nordlinger added: “These are patients who have progressed with heavy chemoregimens and still there is a survival gain, not much—2 months— but the price to pay is low. There is very good safety.” Although the change in median survival was small, the risk of death was significantly lower with TAS-102 than with placebo (hazard ratio 0·68, 95% CI 0·58–0·81; p<0·001), which suggests that the drug might be useful when used in conjuction with other drugs or in different settings. Van Cutsem and colleagues plan to test the drug for earlier stage colorectal cancer and in combination with other active treatments, as well as in other gastrointestinal cancers.
Steve Gschmeissner/Science Photo Library
TAS-102 for metastatic refractory colorectal cancer
Published Online May 22, 2015 http://dx.doi.org/10.1016/ S1470-2045(15)70246-9 For the study by Mayer and colleagues see N Engl J Med 2015; 372: 1909–19
Sean Cleghorn
Androgen deprivation therapy and cognitive impairment? In patients with prostate cancer, androgen deprivation therapy (ADT) might lead to impaired cognitive performance within 6 months of starting treatment, according to a new study. Brian Gonzalez (Moffitt Cancer Center, FL, USA) and colleagues noted that ADT is not only associated with adverse effects (eg, fatigue and depressive symptoms) that interfere with cognitive functioning, but might also directly affect cognitive functioning by lowering testosterone levels. The study included 142 patients with prostate cancer (58 received ADT and 84 underwent only prostatectomy) and 88 agematched and education-matched men without prostate cancer. The researchers assessed how ADT affects cognitive performance, and identified demographic and genetic predictors of impaired cognitive functioning. www.thelancet.com/oncology Vol 16 July 2015
Gonzalez and colleagues showed that, in accordance with the International Cognition and Cancer Task Force criteria, patients with prostate cancer receiving ADT were more likely to show impaired cognitive performance than those in the control group within 6 months (OR 1·71, 95% CI 1·01–2·89) and 12 months (2·42, 1·27–4·61) of treatment commencement. Compared with all controls, recipients of ADT showed increased cognitive impairment over time (p=0·01). According to the researchers, the effects of ADT on impaired cognitive functioning were not moderated by age, baseline cognitive reserve, fatigue, depression, or hot flash interference (p≥0·09 for all comparisons). In the recipients of ADT, increased cognitive impairment over time was associated with a singlenucleotide polymorphism (rs1047776) of the GNB3 gene.
“Given these findings, oncologists may consider discussing cognitive impairment as a possible side-effect of ADT for prostate cancer patients”, commented Gonzalez. He added, “inquiring about cognitive functioning in patients receiving ADT could lead to early diagnosis and treatment for cognitive impairment that may result from ADT”. According to Michael Diefenbach (North Shore-Long Island Jewish Health System, Manhasset, NY, USA), this study is important, carefully undertaken, and should give patients clarity about the possible effect of ADT on their cognitive functioning. “Executive functioning appears to be most affected by ADT, and thus strategies to bolster such functioning need to be developed and evaluated”, he said.
Published Online May 22, 2015 http://dx.doi.org/10.1016/ S1470-2045(15)70247-0 For the study by Gonzalez and colleagues see J Clin Oncol 2015; published online May 11. DOI:10.1200/JCO.2014.60.1963
Sanjeet Bagcchi e314