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Adoptive transfer of T lymphocytes safe and feasible
Newsdesk
Pemetrexed eases treatment for small-cell lung cancer Use of pemetrexed as an adjunct to cisplatin or carboplatin offers more convenient dosing and is less toxic than standard etoposide in treatment of extensive-stage small-cell lung cancer (SCLC), say US investigators (J Clin Oncol 2006; 24: 4840–47). The results of the phase II trial show that combination of a platinum compound and pemetrexed has activity in first-line treatment of extensive-stage (tumours that have spread beyond the supraclavicular regions) SCLC. The combinations were also easy and convenient to administer and had few toxic effects. 78 patients received 500 mg/m² pemetrexed with either cisplatin or carboplatin in standard doses once every 21 days. Median survival was 7·6 months (95% CI 4·9–10·3) in the cisplatin group and 10·4 months (7·4–12·0) in the carboplatin group; survival at 1 year was 33%
(20·6–51·7) in the cisplatin group and 39% (24·0–56·6) in the carboplatin group. 14 (35%) patients in the cisplatin group and 15 (40%) in the carboplatin group showed a response to treatment. “Over the past 20 years, we have really not changed the standard of care”, notes principal investigator Mark Socinski, Lineberger Comprehensive Cancer Center, University of North Carolina in Chapel Hill, NC, USA. None of the current strategies have improved survival, but they have increased toxic effects, he adds. Regimens that contain etoposide are usually given over 3 days; whereas those containing pemetrexed can be administered in 1 day. Therefore, regimens containing pemetrexed “could be as good but more convenient, easier, and less toxic in a disease when the goal is palliation of symptoms”, Socinski says.
Other oncologists are sceptical, though. “The dosing is certainly more convenient”, says Ross Camidge, University of Colorado, Denver, CO, USA. “The more concerning thing relates to the evidence on efficacy. Although the time to progression is in the right range compared with historical controls, the objective response rate is worryingly low (35–40%). Objective response rates of about 80% [are] common with cisplatin–etoposide control groups.” The data presented in this trial suggest that pemetrexed is “unlikely to demonstrate survival superiority or clinically meaningful diminished toxicity compared with etoposide”, says David Johnson, from Vanderbilt University School of Medicine, Nashville, TN, USA. “Further study of these regimens is difficult to justify.”
Paula Moyer
Adoptive transfer of T lymphocytes safe and feasible Cytotoxic T lymphocytes against Epstein-Barr virus (EBV) can be generated routinely from recipients of solid-organ transplantations, then reinfused into these patients to prevent progression of post-transplantation lymphoproliferative disorder (PTLD)
Heart transplantations could benefit from new technique
970
to overt lymphoma in patients, even when these individuals are still receiving immunosuppressive drugs to prevent graft rejection, claim a group of researchers in Blood (2006; 108: 2942–49). “This approach can be used when immunosuppression cannot be reduced because of the risk of graft rejection, which is crucially important, for example, in heart and lung transplantations”, explains lead author Barbara Savoldo (Baylor College of Medicine, Houston, TX, USA). The researchers expanded EBVspecific cytotoxic T lymphocytes from a large cohort of patients who received solid-organ transplantation, including those with active lymphoma. 12 patients at high risk for PTLD, or with active disease, were infused with the lymphocytes. Immunological and virological monitoring after infusion showed that the lymphocytes
proliferated in the patient after infusion and produced complete and stable tumour responses in patients with disease. The treatment was well tolerated, without toxic effects. Andrew Bradley (Addenbrooke’s Hospital, University of Cambridge, UK) notes that the research provides a potential solution to an important therapeutic area because of the severity of this disease. “This treatment is better and more effective than current treatments with fewer toxic effects”, he says. However, he cautions that “this study is only in the early stages of research, showing feasibility and proof of concept. There is still no proof of efficacy in the presence of EBV/ PTLD and the technique used to derive cytotoxic T lymphocytes is complicated, which might have logistical problems in the clinic”.
Anna York
http://oncology.thelancet.com Vol 7 December 2006
Pemetrexed eases treatment for small-cell lung cancer Use of pemetrexed as an adjunct to cisplatin or carboplatin offers more convenient dosing and is less toxic than standard etoposide in treatment of extensive-stage small-cell lung cancer (SCLC), say US investigators (J Clin Oncol 2006; 24: 4840–47). The results of the phase II trial show that combination of a platinum compound and pemetrexed has activity in first-line treatment of extensive-stage (tumours that have spread beyond the supraclavicular regions) SCLC. The combinations were also easy and convenient to administer and had few toxic effects. 78 patients received 500 mg/m² pemetrexed with either cisplatin or carboplatin in standard doses once every 21 days. Median survival was 7·6 months (95% CI 4·9–10·3) in the cisplatin group and 10·4 months (7·4–12·0) in the carboplatin group; survival at 1 year was 33%
(20·6–51·7) in the cisplatin group and 39% (24·0–56·6) in the carboplatin group. 14 (35%) patients in the cisplatin group and 15 (40%) in the carboplatin group showed a response to treatment. “Over the past 20 years, we have really not changed the standard of care”, notes principal investigator Mark Socinski, Lineberger Comprehensive Cancer Center, University of North Carolina in Chapel Hill, NC, USA. None of the current strategies have improved survival, but they have increased toxic effects, he adds. Regimens that contain etoposide are usually given over 3 days; whereas those containing pemetrexed can be administered in 1 day. Therefore, regimens containing pemetrexed “could be as good but more convenient, easier, and less toxic in a disease when the goal is palliation of symptoms”, Socinski says.
Other oncologists are sceptical, though. “The dosing is certainly more convenient”, says Ross Camidge, University of Colorado, Denver, CO, USA. “The more concerning thing relates to the evidence on efficacy. Although the time to progression is in the right range compared with historical controls, the objective response rate is worryingly low (35–40%). Objective response rates of about 80% [are] common with cisplatin–etoposide control groups.” The data presented in this trial suggest that pemetrexed is “unlikely to demonstrate survival superiority or clinically meaningful diminished toxicity compared with etoposide”, says David Johnson, from Vanderbilt University School of Medicine, Nashville, TN, USA. “Further study of these regimens is difficult to justify.”
Paula Moyer
Adoptive transfer of T lymphocytes safe and feasible Cytotoxic T lymphocytes against Epstein-Barr virus (EBV) can be generated routinely from recipients of solid-organ transplantations, then reinfused into these patients to prevent progression of post-transplantation lymphoproliferative disorder (PTLD)
Heart transplantations could benefit from new technique
970
to overt lymphoma in patients, even when these individuals are still receiving immunosuppressive drugs to prevent graft rejection, claim a group of researchers in Blood (2006; 108: 2942–49). “This approach can be used when immunosuppression cannot be reduced because of the risk of graft rejection, which is crucially important, for example, in heart and lung transplantations”, explains lead author Barbara Savoldo (Baylor College of Medicine, Houston, TX, USA). The researchers expanded EBVspecific cytotoxic T lymphocytes from a large cohort of patients who received solid-organ transplantation, including those with active lymphoma. 12 patients at high risk for PTLD, or with active disease, were infused with the lymphocytes. Immunological and virological monitoring after infusion showed that the lymphocytes
proliferated in the patient after infusion and produced complete and stable tumour responses in patients with disease. The treatment was well tolerated, without toxic effects. Andrew Bradley (Addenbrooke’s Hospital, University of Cambridge, UK) notes that the research provides a potential solution to an important therapeutic area because of the severity of this disease. “This treatment is better and more effective than current treatments with fewer toxic effects”, he says. However, he cautions that “this study is only in the early stages of research, showing feasibility and proof of concept. There is still no proof of efficacy in the presence of EBV/ PTLD and the technique used to derive cytotoxic T lymphocytes is complicated, which might have logistical problems in the clinic”.
Anna York
http://oncology.thelancet.com Vol 7 December 2006