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Antiandrogen bone-loss underestimated
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Adoptive transfer of tumour-reactive T cells to patients with metastatic melanoma after immunodepletion can result in tumour regression, researchers have found (Science Sept 19, 2002; DOI: 10.1126/science.1076514). “The key message is that it is possible to divert the majority of the immune system to react against a cancer antigen, and when that occurs the cancer can be made to disappear”, explains lead-author Steve Rosenberg (National Cancer Institute, MD, USA). 13 patients with metastatic melanoma who were refractory to standard treatments, underwent immunodepletion for 7 days and then received about 7.8 x 1010 tumour-reactive T cells and 9 doses of interleukin 2 (IL2). The T cells were derived from tumour-infiltrating lymphocytes and expanded in vitro. Six patients had at least 50% tumour regression lasting for 2–21 months. Tumour sites included lung, liver, lymph nodes, intraperitonium, and cutaneous and subcutaneous tissue. Four patients had partial regression and three had stable disease. “In some patients, over 80% of CD8 killer cells were directed against their cancer antigen. Most cancer-vaccine attempts can raise only 1% (or less) of reactive cells and thus this approach is unique in the strength of the reaction it can induce”, Rosenberg points out. “Transferred T-cell frequencies of this magnitude”, Cassian Yee (Fred Hutchinson Cancer Research Center, WA, USA) adds, “have not been observed before and the responses reported are quite dramatic”. However, he cautions, the study was not without significant toxic effects, and it is not clear what components were essential for the immune response, the persistence of the response, or the treatment efficacy. “There is concern that patients with such a highly skewed repertoire may be immunodeficient in other respects. It is certainly a provocative study and future studies will hopefully be able to define what the essential components are.” Michael Lotze (University of Pittsburgh, USA) says the study shows that T-cell adoptive therapy requires extraordinary manipulation of the host
652
for successful engraftment and antitumor effects, ie, nonmyeloablative chemotherapy and high-dose IL2 with large-scale expansion of T-cells ex vivo. “This is a technical tour de force that shows the capability of T cells in recognising tumours and mediating important antitumour effects”, says Comparison of cells before and after adoptive T-cell therapy. Lotze. Researchers now need to determine tumour, types how production of new whether the clinical responses are T cells that recognise the tumour could durable, how they compare with high- be stimulated. dose IL2 therapy, and, for other Khabir Ahmad
© Science
Adoptive T-cell therapy effective in metastatic melanoma
Antiandrogen bone-loss underestimated Men undergoing antiandrogen therapy for prostate cancer are at a high risk of developing osteoporosis. In addition, bone loss occurs very early during the course of treatment, and very few men have their bone mass or vitamin D status assessed, and even fewer receive bisphosphonate therapy; presentations at the 24th Annual Meeting of the American Society for Bone and Mineral Research (September 20–24, 2002, San Antonio, TX, USA) have shown. Researchers at the University of Pittsburgh, PA, USA, reported that most bone loss occurs within the first 6 months of treatment. In a prospective, longitudinal, 6-month study, they followed a total of 126 men in four groups: 28 patients with prostate cancer not on androgen ablation; 21 on acute therapy (less than 6 months, mean of 3 months); 37 on chronic therapy (more than 6 months, mean of 3 years); and 40 healthy controls. Penelope Coates, lead presenter, says men undergoing acute therapy had a 1·8% reduction in total-body bone mineral density (BMD). They also gained body fat and had increased markers of bone turnover. BMD measurements in the other trial groups remained relatively stable during the study. Cancer patients not on ablative therapy had a 0·52%
decrease in total-body BMD, while chronic therapy patients had a 0·16% reduction, and controls showed a drop of only 0·15%. “Although men with more than 6 months of therapy started the study with a lower BMD than the other men, by 3 years their rate of loss was the same as the controls”, says Coates. In another presentation, researchers from the University of Wisconsin, USA, said the risk of bone loss during antiandrogen therapy is not adequately evaluated or treated. In a retrospective survey, they studied 185 men receiving leuprolide or goserelin for a median of 18 months at the Veterans Affairs Medical Center, Madison, WI, USA, between 1993 and 2001. Study investigator Mary Beth Elliott says that 76% of the men had fracture risk-factors in addition to androgen reduction. These factors included: a past history of fracture, current or former tobacco use, documented alcohol abuse, a body-massindex less than 25 kg/m2, or long-term prednisone or antiepileptic drug use. Despite this, only 16% of men received a bone mass measurement, only 6% were assessed for vitamin D status, and only 16% received bisphosphonate therapy during the study period. Robert H Carlson
THE LANCET Oncology Vol 3 November 2002
http://oncology.thelancet.com
For personal use. Only reproduce with permission from The Lancet Publishing Group.
Adoptive transfer of tumour-reactive T cells to patients with metastatic melanoma after immunodepletion can result in tumour regression, researchers have found (Science Sept 19, 2002; DOI: 10.1126/science.1076514). “The key message is that it is possible to divert the majority of the immune system to react against a cancer antigen, and when that occurs the cancer can be made to disappear”, explains lead-author Steve Rosenberg (National Cancer Institute, MD, USA). 13 patients with metastatic melanoma who were refractory to standard treatments, underwent immunodepletion for 7 days and then received about 7.8 x 1010 tumour-reactive T cells and 9 doses of interleukin 2 (IL2). The T cells were derived from tumour-infiltrating lymphocytes and expanded in vitro. Six patients had at least 50% tumour regression lasting for 2–21 months. Tumour sites included lung, liver, lymph nodes, intraperitonium, and cutaneous and subcutaneous tissue. Four patients had partial regression and three had stable disease. “In some patients, over 80% of CD8 killer cells were directed against their cancer antigen. Most cancer-vaccine attempts can raise only 1% (or less) of reactive cells and thus this approach is unique in the strength of the reaction it can induce”, Rosenberg points out. “Transferred T-cell frequencies of this magnitude”, Cassian Yee (Fred Hutchinson Cancer Research Center, WA, USA) adds, “have not been observed before and the responses reported are quite dramatic”. However, he cautions, the study was not without significant toxic effects, and it is not clear what components were essential for the immune response, the persistence of the response, or the treatment efficacy. “There is concern that patients with such a highly skewed repertoire may be immunodeficient in other respects. It is certainly a provocative study and future studies will hopefully be able to define what the essential components are.” Michael Lotze (University of Pittsburgh, USA) says the study shows that T-cell adoptive therapy requires extraordinary manipulation of the host
652
for successful engraftment and antitumor effects, ie, nonmyeloablative chemotherapy and high-dose IL2 with large-scale expansion of T-cells ex vivo. “This is a technical tour de force that shows the capability of T cells in recognising tumours and mediating important antitumour effects”, says Comparison of cells before and after adoptive T-cell therapy. Lotze. Researchers now need to determine tumour, types how production of new whether the clinical responses are T cells that recognise the tumour could durable, how they compare with high- be stimulated. dose IL2 therapy, and, for other Khabir Ahmad
© Science
Adoptive T-cell therapy effective in metastatic melanoma
Antiandrogen bone-loss underestimated Men undergoing antiandrogen therapy for prostate cancer are at a high risk of developing osteoporosis. In addition, bone loss occurs very early during the course of treatment, and very few men have their bone mass or vitamin D status assessed, and even fewer receive bisphosphonate therapy; presentations at the 24th Annual Meeting of the American Society for Bone and Mineral Research (September 20–24, 2002, San Antonio, TX, USA) have shown. Researchers at the University of Pittsburgh, PA, USA, reported that most bone loss occurs within the first 6 months of treatment. In a prospective, longitudinal, 6-month study, they followed a total of 126 men in four groups: 28 patients with prostate cancer not on androgen ablation; 21 on acute therapy (less than 6 months, mean of 3 months); 37 on chronic therapy (more than 6 months, mean of 3 years); and 40 healthy controls. Penelope Coates, lead presenter, says men undergoing acute therapy had a 1·8% reduction in total-body bone mineral density (BMD). They also gained body fat and had increased markers of bone turnover. BMD measurements in the other trial groups remained relatively stable during the study. Cancer patients not on ablative therapy had a 0·52%
decrease in total-body BMD, while chronic therapy patients had a 0·16% reduction, and controls showed a drop of only 0·15%. “Although men with more than 6 months of therapy started the study with a lower BMD than the other men, by 3 years their rate of loss was the same as the controls”, says Coates. In another presentation, researchers from the University of Wisconsin, USA, said the risk of bone loss during antiandrogen therapy is not adequately evaluated or treated. In a retrospective survey, they studied 185 men receiving leuprolide or goserelin for a median of 18 months at the Veterans Affairs Medical Center, Madison, WI, USA, between 1993 and 2001. Study investigator Mary Beth Elliott says that 76% of the men had fracture risk-factors in addition to androgen reduction. These factors included: a past history of fracture, current or former tobacco use, documented alcohol abuse, a body-massindex less than 25 kg/m2, or long-term prednisone or antiepileptic drug use. Despite this, only 16% of men received a bone mass measurement, only 6% were assessed for vitamin D status, and only 16% received bisphosphonate therapy during the study period. Robert H Carlson
THE LANCET Oncology Vol 3 November 2002
http://oncology.thelancet.com
For personal use. Only reproduce with permission from The Lancet Publishing Group.