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Less toxic treatment for multiple myeloma
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Tamoxifen better than arzoxifene in breast cancer
Steve Gschmeissner/SPL
Arzoxifene does not have better antitumour activity than tamoxifen (J Clin Oncol 2007; 25: 4967–73). “In earlier phase II studies, arzoxifene [a selective oestrogen-receptor modulator (SERM)] demonstrated significant antitumour activity, and also had a good safety profile, but the
Does arzoxifene have a role in treatment of breast cancer?
effect demonstrated by this drug in the current phase III trial is lower than anticipated”, says senior author Aman Buzdar (MD Anderson Cancer Center, Houston, TX, USA) Patients with oestrogen-receptorpositive or progesterone-receptor-positive locally advanced or metastatic breast cancer were randomly assigned to 20 mg of arzoxifene or 20 mg of tamoxifen per day. Planned total accrual was 240 patients. However, a planned interim analysis of the first 200 patients showed a lower response for patients assigned to arzoxifene then those assigned to tamoxifen, so further enrollment was stopped. The authors report the analysis of 352 patients who had been randomly assigned when enrollment was stopped. Median progression-free survival was 7·5 months for the tamoxifen group (95% CI 5·9–8·84) compared with 4 months (3·4–5·6) for the arzoxifene group, and tamoxifen
was shown to have longer time to treatment failure (p=0·003). “Our reports may result in minimal interest in arzoxifene’s further development, but based on the rat data, it may find its use in osteoporosis and reduction of risk of invasive breast cancer in post-menopausal women where it is more potent than raloxifene”, says Buzdar. However, Michael DeGregorio (University of California, Sacramento, CA, USA) does not think that arzoxifene will be superior to raloxifene, which has just received FDA approval for reducing the risk of invasive breast cancer in postmenopausal women. He adds “clearly, arzoxifene has followed in the footsteps of other SERMs such as droloxifene and idoxifene, both of which failed to demonstrate superior clinical efficacy in studies”.
Sharan Prakash Sharma
Less toxic treatment for multiple myeloma Patients with multiple myeloma treated with cyclophosphamide and dexamethasone (Cy-Dex) before high-dose chemotherapy and stemcell transplantation have responses comparable to those of patients given a more toxic, older regimen of vincristine, doxorubicin, and dexamethasone (VAD; Cancer published online Oct 31, 2007; DOI:10.1002/cncr.23145). 319 newly diagnosed patients with multiple myeloma were randomly assigned to two cycles of Cy-Dex or three doses of VAD as induction treatment given before consolidation treatment with highdose melphalan and autologous stemcell transplantation (ASCT). Patients receiving Cy-Dex had lower mortality in the first 4 months after treatment than those assigned VAD (1·9% vs 5·8%, p=0·08). Both groups had a median event-free survival of 29 months, with a 75% overall survival at 3 years. All 1058
patients underwent stem-cell harvest 4–6 weeks after induction treatment and took high-dose melphalan 4–6 weeks after stem-cell harvest. 80% of patients assigned VAD achieved at least a partial response, compared with 81% of those assigned to Cy-Dex post-ASCT. “In Scandanavian countries, CyDex is now recommended as initial treatment for patients suited for ASCT”, says first author Ulf-Henrik Mellqvist, (Sahlgrenska University Hospital, Gothenburg, Sweden). “One reason why centres adapted Cy-Dex so quickly is because it is very easy to administer—it can be given in an outpatient setting in 1 hour, whereas VAD requires a central venous access and a 4-day hospital stay.” “I am not surprised by these results”, comments Ruben Niesvizky (Weill Cornell Medical College, New York, NY, USA). “We have learned that vincristine
is not active against myeloma, doxorubicin has only borderline activity, whereas dexamethasone is the active component of VAD. VAD should be discontinued, as other research shows better results with other drugs”, he adds. Studies have shown that bortezomib, thalidomide, and a derivative, lenalidomide, are better—ie, more active and less toxic then VAD—and these and other drugs have largely replaced VAD in the USA, says Niesvizky. “Cyclophosphamide also improves the number of stem cells that can be mobilised and collected.” Mellqvist’s group is now testing bortezomib as a consolidation treatment. “It is a good strategy to bring patients rapidly and with minimum toxicity to ASCT and to focus on consolidation or maintenance therapy afterwards”, says Mellqvist.
Vicki Brower
http://oncology.thelancet.com Vol 8 December 2007
Tamoxifen better than arzoxifene in breast cancer
Steve Gschmeissner/SPL
Arzoxifene does not have better antitumour activity than tamoxifen (J Clin Oncol 2007; 25: 4967–73). “In earlier phase II studies, arzoxifene [a selective oestrogen-receptor modulator (SERM)] demonstrated significant antitumour activity, and also had a good safety profile, but the
Does arzoxifene have a role in treatment of breast cancer?
effect demonstrated by this drug in the current phase III trial is lower than anticipated”, says senior author Aman Buzdar (MD Anderson Cancer Center, Houston, TX, USA) Patients with oestrogen-receptorpositive or progesterone-receptor-positive locally advanced or metastatic breast cancer were randomly assigned to 20 mg of arzoxifene or 20 mg of tamoxifen per day. Planned total accrual was 240 patients. However, a planned interim analysis of the first 200 patients showed a lower response for patients assigned to arzoxifene then those assigned to tamoxifen, so further enrollment was stopped. The authors report the analysis of 352 patients who had been randomly assigned when enrollment was stopped. Median progression-free survival was 7·5 months for the tamoxifen group (95% CI 5·9–8·84) compared with 4 months (3·4–5·6) for the arzoxifene group, and tamoxifen
was shown to have longer time to treatment failure (p=0·003). “Our reports may result in minimal interest in arzoxifene’s further development, but based on the rat data, it may find its use in osteoporosis and reduction of risk of invasive breast cancer in post-menopausal women where it is more potent than raloxifene”, says Buzdar. However, Michael DeGregorio (University of California, Sacramento, CA, USA) does not think that arzoxifene will be superior to raloxifene, which has just received FDA approval for reducing the risk of invasive breast cancer in postmenopausal women. He adds “clearly, arzoxifene has followed in the footsteps of other SERMs such as droloxifene and idoxifene, both of which failed to demonstrate superior clinical efficacy in studies”.
Sharan Prakash Sharma
Less toxic treatment for multiple myeloma Patients with multiple myeloma treated with cyclophosphamide and dexamethasone (Cy-Dex) before high-dose chemotherapy and stemcell transplantation have responses comparable to those of patients given a more toxic, older regimen of vincristine, doxorubicin, and dexamethasone (VAD; Cancer published online Oct 31, 2007; DOI:10.1002/cncr.23145). 319 newly diagnosed patients with multiple myeloma were randomly assigned to two cycles of Cy-Dex or three doses of VAD as induction treatment given before consolidation treatment with highdose melphalan and autologous stemcell transplantation (ASCT). Patients receiving Cy-Dex had lower mortality in the first 4 months after treatment than those assigned VAD (1·9% vs 5·8%, p=0·08). Both groups had a median event-free survival of 29 months, with a 75% overall survival at 3 years. All 1058
patients underwent stem-cell harvest 4–6 weeks after induction treatment and took high-dose melphalan 4–6 weeks after stem-cell harvest. 80% of patients assigned VAD achieved at least a partial response, compared with 81% of those assigned to Cy-Dex post-ASCT. “In Scandanavian countries, CyDex is now recommended as initial treatment for patients suited for ASCT”, says first author Ulf-Henrik Mellqvist, (Sahlgrenska University Hospital, Gothenburg, Sweden). “One reason why centres adapted Cy-Dex so quickly is because it is very easy to administer—it can be given in an outpatient setting in 1 hour, whereas VAD requires a central venous access and a 4-day hospital stay.” “I am not surprised by these results”, comments Ruben Niesvizky (Weill Cornell Medical College, New York, NY, USA). “We have learned that vincristine
is not active against myeloma, doxorubicin has only borderline activity, whereas dexamethasone is the active component of VAD. VAD should be discontinued, as other research shows better results with other drugs”, he adds. Studies have shown that bortezomib, thalidomide, and a derivative, lenalidomide, are better—ie, more active and less toxic then VAD—and these and other drugs have largely replaced VAD in the USA, says Niesvizky. “Cyclophosphamide also improves the number of stem cells that can be mobilised and collected.” Mellqvist’s group is now testing bortezomib as a consolidation treatment. “It is a good strategy to bring patients rapidly and with minimum toxicity to ASCT and to focus on consolidation or maintenance therapy afterwards”, says Mellqvist.
Vicki Brower
http://oncology.thelancet.com Vol 8 December 2007