NEW YORK (Reuters Health) Oct 04 - Continuous once-daily sunitinib is a feasible regimen for first-line treatment of advanced/metastatic renal cell carcinoma, when necessary, and might benefit selected patients, researchers say.
When the drug received FDA approval in 2007 the dosing schedule was 50 mg per day, 4 weeks on and 2 weeks off, as Dr. Carlos H. Barrios of PUCRS School of Medicine, Porto Alegre, Brazil and colleagues note in their report.
The continuous dosing regimen wasn't superior to the approved protocol in their study. However, it might prove useful in patients who develop symptoms in the off-treatment period, the investigators say.
They treated 119 treatment-naive patients with 37.5 mg daily for a median of 24.3 weeks, according to a September 6th online paper in Cancer.
The objective response rate was 35.3% and the median response duration was 10.4 months. Overall, 36% of patients had stable disease for at least 12 weeks. The one-year survival probability was 67.8%.
The median progression-free survival was nine months, shorter than the 11 months seen in the phase III trial with the intermittent 50 mg dosing.
Dosing delays were less frequent in the current study (18% vs 38%) but a similar proportion of patients required a dose reduction (33% vs 32%). A comparable proportion of patients discontinued treatment because of an adverse event.
Overall, the researchers favor the approved intermittent schedule, which showed trends toward a longer time to tumor progression and a longer progression-free survival, and a statistically superior time to deterioration.
Still, they say continuous dosing might be preferable in select circumstances, for example, when patients have tumor regrowth or symptom flare during the two-week off-treatment period.
"The regimen," Dr. Barrios told Reuters Health by email, "proved to be active with manageable toxicity. However, even though this was not a comparative trial we did not encounter any signal that the toxicity observed was significantly different from what we would have expected with the approved 4/2 regimen. Nevertheless the regimen could represent an alternative for individual patients that could potentially adapt better to this schedule."
In an editorial, Dr. Brian I. Rini of The Cleveland Clinic Taussig Cancer Institute, Ohio and Dr. Cristina Suarez of Hospital General Vall d'Hebron, Barcelona, Spain note that the most recently published study, a randomized trial comparing the two regimens, "supports clear advantages for the 50-mg dose using the 4/2 schedule."
Nevertheless, investigation is ongoing, and Dr. Rini told Reuters Health by email that the current data "extend the experience of alternative dosing of sunitinib. It is clear that dose and schedule impact outcome, and there is still more work to do to understand how to optimize giving targeted agents like sunitinib."
SOURCE: http://bit.ly/nbSQgd
When the drug received FDA approval in 2007 the dosing schedule was 50 mg per day, 4 weeks on and 2 weeks off, as Dr. Carlos H. Barrios of PUCRS School of Medicine, Porto Alegre, Brazil and colleagues note in their report.
The continuous dosing regimen wasn't superior to the approved protocol in their study. However, it might prove useful in patients who develop symptoms in the off-treatment period, the investigators say.
They treated 119 treatment-naive patients with 37.5 mg daily for a median of 24.3 weeks, according to a September 6th online paper in Cancer.
The objective response rate was 35.3% and the median response duration was 10.4 months. Overall, 36% of patients had stable disease for at least 12 weeks. The one-year survival probability was 67.8%.
The median progression-free survival was nine months, shorter than the 11 months seen in the phase III trial with the intermittent 50 mg dosing.
Dosing delays were less frequent in the current study (18% vs 38%) but a similar proportion of patients required a dose reduction (33% vs 32%). A comparable proportion of patients discontinued treatment because of an adverse event.
Overall, the researchers favor the approved intermittent schedule, which showed trends toward a longer time to tumor progression and a longer progression-free survival, and a statistically superior time to deterioration.
Still, they say continuous dosing might be preferable in select circumstances, for example, when patients have tumor regrowth or symptom flare during the two-week off-treatment period.
"The regimen," Dr. Barrios told Reuters Health by email, "proved to be active with manageable toxicity. However, even though this was not a comparative trial we did not encounter any signal that the toxicity observed was significantly different from what we would have expected with the approved 4/2 regimen. Nevertheless the regimen could represent an alternative for individual patients that could potentially adapt better to this schedule."
In an editorial, Dr. Brian I. Rini of The Cleveland Clinic Taussig Cancer Institute, Ohio and Dr. Cristina Suarez of Hospital General Vall d'Hebron, Barcelona, Spain note that the most recently published study, a randomized trial comparing the two regimens, "supports clear advantages for the 50-mg dose using the 4/2 schedule."
Nevertheless, investigation is ongoing, and Dr. Rini told Reuters Health by email that the current data "extend the experience of alternative dosing of sunitinib. It is clear that dose and schedule impact outcome, and there is still more work to do to understand how to optimize giving targeted agents like sunitinib."
SOURCE: http://bit.ly/nbSQgd
Δεν υπάρχουν σχόλια:
Δημοσίευση σχολίου