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Bevacizumab for radiation retinopathy
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Testing times for multiple myeloma drug combinations Prior treatment with thalidomide or lenalidomide—immunomodulators widely used for first-line treatment of multiple myeloma—does not affect the safety or efficacy of use of pegylated liposomal doxorubicin (PLD) plus bortezomib in patients with recurrent or refractory multiple myeloma, according to a prespecified subgroup analysis from a phase III trial (Cancer, published online Feb 25, 2008; DOI:10.1002/ cncr.23326). Of note, says first author Pieter Sonneveld (Erasmus Medical Center, Rotterdam, Netherlands), “the PLD and bortezomib combination is more effective than bortezomib alone in both immunomodulator-naive and immunomodulator-exposed patients”. In the past decade, new drugs such as bortezomib and immunomodulators have greatly improved the outcome of patients with multiple myeloma. Nevertheless, median survival of these patients is still only 5–7 years and
researchers are now trying to optimise outcomes by combining these new agents with traditional chemotherapy drugs such as doxorubicin. But whether patient outcome is affected by the order in which the various agents are given is unknown. Sonneveld and colleagues therefore assessed whether prior treatment with immunomodulatory drugs affected the time to progression (TTP) of patients with relapsed or refractory myeloma who were randomly assigned to PLD with bortezomib or to bortezomib alone. They noted no significant difference in TTP between 194 immunomodulator-naive patients and 130 immunomodulator-exposed patients who were randomly assigned to the combination group (295 days and 270 days, respectively; p=0·446). These two groups also had similar durations of response and similar incidence of drug-related adverse
events. By contrast, however, in the immunomodulator-exposed group, the TTP was significantly longer for those who were randomly assigned to the combination than for those assigned to bortezomib alone (270 days vs 205 days, HR 1·62, 95% CI 1·08–2·41), a finding similar to that noted previously for the whole study population (J Clin Oncol 2007; 25: 3892–901). “These results are important and support the role of new drug combinations in relapsed myeloma”, comments Paul Richardson (DanaFarber Cancer Institute, Boston, MA, USA). “They suggest that the combination of bortezomib with PLD should be considered as salvage therapy for patients who progress after thalidomide or lenalidomide treatment, and especially in those with aggressive relapse.”
Jane Bradbury
Bevacizumab for radiation retinopathy
http://oncology.thelancet.com Vol 9 April 2008
“Anywhere between 40% and 80% of patients who receive ocular irradiation for choroidal melanoma will develop radiation retinopathy within 5 years.” To inhibit VEGF, Finger intraocularly injected bevacizumab (1·25 mg in 0·05 mL every 6–12 weeks; mean number of injections 3·8), a humanised anti-VEGF monoclonal antibody, into the affected eyes of 21 patients who developed radiation retinopathy after palladium-103 plaque brachytherapy or iodine-125 irradiation for choroidal melanoma. Median follow-up time was 7·8 months (range 2–18). “Ophthalmic imaging showed treatment led to exudate and haemorrhage resolution, but mostly to reduced vascular transudation and oedema”, explains Finger. “In 18 patients visual acuity was stabilised or even improved; the reduction seen in oedema probably allowed the macular retinal nerves to recover [figure B].”
“We have been using bevacizumab for radiation retinopathy…and some patients have experienced remarkable benefit“, adds Bertil Damato (Liverpool Ocular Oncology Centre, Liverpool, UK). “When retinopathy is caused by fluid leakage from the irradiated tumour itself, however, we have also found it useful to close the leaking tumour vessels with laser treatment or to remove the [tumour] surgically.“
Adrian Burton A
B
Courtesy of Paul Finger
Bevacizumab can be used to treat radiation retinopathy and perhaps prevent eventual blindness (Int J Radiat Oncol Biol Phys 2008; 70: 974–77). Radiation retinopathy is a complication of ocular radiotherapy, and causes obliterative arteritis. Vascular closure induces an upregulation of vascular endothelial growth factor (VEGF) expression, leading to vascular transudation, oedema, necrosis, neovascularisation, retinal haemorrhage, cotton-wool spots, and exudates (figure A). Radiation retinopathy can also cause vitreous haemorrhage, and neovascular glaucoma, which can lead to blindness. “The risk of developing radiation retinopathy depends on the radiation dose, whether a person has received radiation sensitisers, on the presence of comorbid conditions such as diabetes, and the type of radiation treatment”, explains Paul Finger (New York Eye Cancer Center, New York, USA).
Retinal appearance before (A) and after (B) bevacizumab treatment
325
Testing times for multiple myeloma drug combinations Prior treatment with thalidomide or lenalidomide—immunomodulators widely used for first-line treatment of multiple myeloma—does not affect the safety or efficacy of use of pegylated liposomal doxorubicin (PLD) plus bortezomib in patients with recurrent or refractory multiple myeloma, according to a prespecified subgroup analysis from a phase III trial (Cancer, published online Feb 25, 2008; DOI:10.1002/ cncr.23326). Of note, says first author Pieter Sonneveld (Erasmus Medical Center, Rotterdam, Netherlands), “the PLD and bortezomib combination is more effective than bortezomib alone in both immunomodulator-naive and immunomodulator-exposed patients”. In the past decade, new drugs such as bortezomib and immunomodulators have greatly improved the outcome of patients with multiple myeloma. Nevertheless, median survival of these patients is still only 5–7 years and
researchers are now trying to optimise outcomes by combining these new agents with traditional chemotherapy drugs such as doxorubicin. But whether patient outcome is affected by the order in which the various agents are given is unknown. Sonneveld and colleagues therefore assessed whether prior treatment with immunomodulatory drugs affected the time to progression (TTP) of patients with relapsed or refractory myeloma who were randomly assigned to PLD with bortezomib or to bortezomib alone. They noted no significant difference in TTP between 194 immunomodulator-naive patients and 130 immunomodulator-exposed patients who were randomly assigned to the combination group (295 days and 270 days, respectively; p=0·446). These two groups also had similar durations of response and similar incidence of drug-related adverse
events. By contrast, however, in the immunomodulator-exposed group, the TTP was significantly longer for those who were randomly assigned to the combination than for those assigned to bortezomib alone (270 days vs 205 days, HR 1·62, 95% CI 1·08–2·41), a finding similar to that noted previously for the whole study population (J Clin Oncol 2007; 25: 3892–901). “These results are important and support the role of new drug combinations in relapsed myeloma”, comments Paul Richardson (DanaFarber Cancer Institute, Boston, MA, USA). “They suggest that the combination of bortezomib with PLD should be considered as salvage therapy for patients who progress after thalidomide or lenalidomide treatment, and especially in those with aggressive relapse.”
Jane Bradbury
Bevacizumab for radiation retinopathy
http://oncology.thelancet.com Vol 9 April 2008
“Anywhere between 40% and 80% of patients who receive ocular irradiation for choroidal melanoma will develop radiation retinopathy within 5 years.” To inhibit VEGF, Finger intraocularly injected bevacizumab (1·25 mg in 0·05 mL every 6–12 weeks; mean number of injections 3·8), a humanised anti-VEGF monoclonal antibody, into the affected eyes of 21 patients who developed radiation retinopathy after palladium-103 plaque brachytherapy or iodine-125 irradiation for choroidal melanoma. Median follow-up time was 7·8 months (range 2–18). “Ophthalmic imaging showed treatment led to exudate and haemorrhage resolution, but mostly to reduced vascular transudation and oedema”, explains Finger. “In 18 patients visual acuity was stabilised or even improved; the reduction seen in oedema probably allowed the macular retinal nerves to recover [figure B].”
“We have been using bevacizumab for radiation retinopathy…and some patients have experienced remarkable benefit“, adds Bertil Damato (Liverpool Ocular Oncology Centre, Liverpool, UK). “When retinopathy is caused by fluid leakage from the irradiated tumour itself, however, we have also found it useful to close the leaking tumour vessels with laser treatment or to remove the [tumour] surgically.“
Adrian Burton A
B
Courtesy of Paul Finger
Bevacizumab can be used to treat radiation retinopathy and perhaps prevent eventual blindness (Int J Radiat Oncol Biol Phys 2008; 70: 974–77). Radiation retinopathy is a complication of ocular radiotherapy, and causes obliterative arteritis. Vascular closure induces an upregulation of vascular endothelial growth factor (VEGF) expression, leading to vascular transudation, oedema, necrosis, neovascularisation, retinal haemorrhage, cotton-wool spots, and exudates (figure A). Radiation retinopathy can also cause vitreous haemorrhage, and neovascular glaucoma, which can lead to blindness. “The risk of developing radiation retinopathy depends on the radiation dose, whether a person has received radiation sensitisers, on the presence of comorbid conditions such as diabetes, and the type of radiation treatment”, explains Paul Finger (New York Eye Cancer Center, New York, USA).
Retinal appearance before (A) and after (B) bevacizumab treatment
325