Each radiation and temozolomide, a generic chemotherapy remedy in tablet type, have significant single-modality anti-tumor exercise in opposition to slow-growing, low-grade gliomas. The randomized part 3 trial E3F05 by the ECOG-ACRIN Most cancers Analysis Group (ECOG-ACRIN) examined whether or not mixed remedy utilizing temozolomide alongside radiation remedy is more practical than radiation remedy alone in these sufferers. The trial adopted 172 sufferers for greater than 10 years, and its outcomes have an instantaneous scientific affect by offering the primary proof from a randomized part 3 trial that temozolomide improves long-term survival for these sufferers.
We discovered that the 10-year survival price was 70% with the mixed remedy with temozolomide chemotherapy and radiation, in comparison with 47% with radiation alone because the preliminary method. This discovery is necessary as a result of till now, we’ve not had compelling proof that temozolomide improves general survival in grade 2 gliomas.”
David Schiff, MD, lead investigator, the Harrison Distinguished Professor of Neurology, Neurological Surgical procedure and Medication and co-director, UVA Neuro-Oncology Middle, College of Virginia
Dr. Schiff introduced the hanging outcomes as a late-breaking summary on the Society of Neuro-Oncology’s 2024 SNO Annual Assembly. The trial was funded by the US Nationwide Institutes of Well being’s Nationwide Most cancers Institute via its Nationwide Medical Trials Community (NCTN).
The E3F05 trial began in September 2009 and enrolled sufferers with low-grade gliomas who had not acquired prior radiation or chemotherapy remedy. Trial individuals have been randomized 1:1 to obtain both radiation alone (50.4 Gy in 28 fractions) or radiation (50.4 Gy) with temozolomide adopted by 12 four-week cycles of post-radiation temozolomide).
Accrual stopped 5 years later, in 2014, after one other cooperative group trial, RTOG 9802 (additionally funded by the NCI) reported profit from the addition of PCV chemotherapy to radiation in grade 2 gliomas. PCV is procarbazine (P), CCNU (C), which generically is called lomustine, and vincristine (V). By the point accrual stopped, 172 sufferers had enrolled in E3F05. The median age of the 172 individuals was 44 (vary 19-78), and 54% have been male.
“As a result of the RTOG 9802 trial was constructive for a profit from PCV chemotherapy, it was now not moral to have a radiation-alone arm in E3F05, which is why our trial was closed to accrual. Regardless that we couldn’t enroll your entire group as deliberate, after following all sufferers on the trial, outcomes reached statistical significance displaying the advantage of combined-modality temozolomide versus radiation alone,” stated Dr. Schiff.
The outcomes of this trial may have an instantaneous scientific affect.
“Because the outcomes of RTOG 9802 got here out in 2014, sufferers with grade 2 glioma are routinely receiving radiation plus chemotherapy. Some are getting PCV as a result of that’s what RTOG confirmed was helpful. Others are getting radiation plus temozolomide as a result of temozolomide is rather a lot simpler for the oncologist to present and rather a lot much less poisonous for sufferers to take, and it would not contain an intravenous infusion of vincristine. However till now, there actually was no supporting proof in grade 2 gliomas that temozolomide was helpful,” stated Dr. Schiff.
Whereas grade 3 or larger toxicity was extra frequent in E3F05 trial individuals handled with temozolomide in comparison with radiation, toxicity was in keeping with prior research of temozolomide.
“There have been no sudden toxicities from the addition of temozolomide,” stated Dr. Schiff. “We noticed extra fatigue, gastrointestinal misery (nausea), and myelosuppression (thrombocytopenia, neutropenia, and many others.) however similar to what has been reported many, many occasions.”
He added, “Importantly, the magnitude of survival profit from the addition of temozolomide was related in oligodendrogliomas and astrocytomas. This discovering stands in distinction to some uncontrolled and retrospective research suggesting that temozolomide could also be considerably much less efficient in opposition to oligodendrogliomas than PCV.”
There’s extra to return from E3F05. Pending correlative research are investigating the standard of life and neurocognitive knowledge collected from sufferers on each arms of the research, in addition to extra molecular analyses.