Temodar 6 cycles (European protocol) vs 12 cycles (U.S. protocol)
My 61 yr old husband, who was diagnosed May 1, 2015 with GBM, just finished his 6th round of Temodar. The usual protocol in Europe is only 6 rounds, we have a friend who is a neuro-onc in Scotland suggesting that more than 6 is not impactful. Our U.S. doctor and the U.S. protocol is for a full 12 rounds. In this last round of chemo, my husband is having a harder time recovering. He is struggling with short-term memory loss, exhaustion and most frightening is the lack of appetite, weight loss. It seems he is taking longer and longer to recoup from chemo, is it worth it?
My mom's neurooncologist seems to think that there is a potential there isn't even much benefit from the first 6 cycles of TMZ and that that all the benefit we see from treatment of GBM could be from the 6 weeks of combined TMZ/radiation. Has anyone else heard about this?
I'm not sure how that relates to the 2-year, 3-year, and 5-year survival data.
There was a well-designed retrospective study conducted by a number of well-known clinicians including Roger Stupp, Mark Gilbert, Martin van den Bent, Monika Hegi, Michael Weller etc., published as an abstract for SNO 2015. It showed significantly increased PFS in patients undergoing more than 6 cycles, esp. those with MGMT methylation. However, quality-of-life and tolerability should also inform such a decision. The text of the abstract is as follows:
"BACKGROUND: Following maximal safe resection, radiation (RT) with concurrent and 6 cycles (C) of adjuvant temozolomide (TMZ) [Stupp NEJM 2005] has been established as standard of care for newly-diagnosed glioblastoma(GBM).This regimen has been adopted with variations,including extending TMZ beyond 6 cycles.The optimal duration of maintenance therapy remains a matter of debate.
OBJECTIVES:Compare outcomes of patients who completed 6C of TMZ and discontinued treatment to those of patients who continued TMZ >6C.
METHODOLOGY:We performed a pooled analysis of 4 randomized trials (EORTC/NCIC 26981-CE.3; EORTC26071-CENTRIC; EMD- CORE; RTOG 0525-Intergroup). All patients received the standard of care (TMZ/RTwithTMZ).All patients who completed TMZ 6C and had not progressed within 28 days were included.Based on local practice and the discretion of the investigator TMZ could be continued for up to 12C. Patients were grouped into those who completed 6C TMZ and those who continued >6C; progression-free and overall survival were analyzed, adjusted by age, performance status, resection extent, and MGMT status. Exploratory analyses with and without MGMT data imputation were performed at 5% significance.
RESULTS: Independent of evaluated prognostic factors, treatment with >6C TMZ was significantly associated with improved PFS [HR 0.77 (0.61-0.97),p = 0.03]. This effect was more pronounced in patients with methylated MGMT [HR 0.64 (0.47-0.88), p = 0.01]. However, OS was not affected by the number of TMZ cycles, including the MGMT methylated subgroup (p = 0.99). Prognostic factors between 6C vs >6C groups were well-balanced, except MGMT methylation status; methylated status was less frequent in patients receiving >6C (39% vs 62%). Prognostic factors including age, MGMT methylation, extent of resection, and performance status had an expected impact on outcomes.
CONCLUSION: Increasing the number of cycles of TMZ beyond 6 months is not shown to increase OS. PFS was improved, more so in patients with MGMT-methylated tumors."
My mom's neurooncologist seems to think that there is a potential there isn't even much benefit from the first 6 cycles of TMZ and that that all the benefit we see from treatment of GBM could be from the 6 weeks of combined TMZ/radiation. Has anyone else heard about this?
ReplyDeleteI'm not sure how that relates to the 2-year, 3-year, and 5-year survival data.
There was a well-designed retrospective study conducted by a number of well-known clinicians including Roger Stupp, Mark Gilbert, Martin van den Bent, Monika Hegi, Michael Weller etc., published as an abstract for SNO 2015. It showed significantly increased PFS in patients undergoing more than 6 cycles, esp. those with MGMT methylation. However, quality-of-life and tolerability should also inform such a decision. The text of the abstract is as follows:
ReplyDelete"BACKGROUND: Following maximal safe resection, radiation (RT) with
concurrent and 6 cycles (C) of adjuvant temozolomide (TMZ) [Stupp NEJM
2005] has been established as standard of care for newly-diagnosed glioblastoma(GBM).This regimen has been adopted with variations,including extending TMZ beyond 6 cycles.The optimal duration of maintenance therapy remains a matter of debate.
OBJECTIVES:Compare outcomes of patients who completed
6C of TMZ and discontinued treatment to those of patients who continued
TMZ >6C.
METHODOLOGY:We performed a pooled analysis of 4 randomized trials (EORTC/NCIC 26981-CE.3; EORTC26071-CENTRIC; EMD-
CORE; RTOG 0525-Intergroup). All patients received the standard of care (TMZ/RTwithTMZ).All patients who completed TMZ 6C and had not progressed within 28 days were included.Based on local practice and the discretion of the investigator TMZ could be continued for up to 12C. Patients were grouped into those who completed 6C TMZ and those who continued >6C;
progression-free and overall survival were analyzed, adjusted by age, performance status, resection extent, and MGMT status. Exploratory analyses with
and without MGMT data imputation were performed at 5% significance.
RESULTS: Independent of evaluated prognostic factors, treatment with >6C
TMZ was significantly associated with improved PFS [HR 0.77 (0.61-0.97),p = 0.03]. This effect was more pronounced in patients with methylated MGMT [HR 0.64 (0.47-0.88), p = 0.01]. However, OS was not affected by the number of TMZ cycles, including the MGMT methylated subgroup (p = 0.99). Prognostic factors between 6C vs >6C groups were well-balanced, except MGMT methylation status; methylated status was less frequent in patients receiving >6C (39% vs 62%). Prognostic factors including age,
MGMT methylation, extent of resection, and performance status had an expected impact on outcomes.
CONCLUSION: Increasing the number of cycles of
TMZ beyond 6 months is not shown to increase OS. PFS was improved, more so in patients with MGMT-methylated tumors."