This summer saw the publication* in the New England Journal of Medicine of a small clinical trial where ten individuals with NF2-related vestibular schwannomas were treated with the VEGF-blockade drug bevacizumab (more commonly known by the trade name Avastin). Four patients showed sustained tumor volume reduction and four patients showed some improvement in hearing function. The study was met with excitement by the NF2 professional and patient community and was widely reported in the media. Today’s NEJM** includes two ‘letters to the editor’ on this paper.
One letter from Dr. Orlando Guntinas-Lichius, Friedrich Schiller University of Jena, Germany comments that the correlation between NF2 vestibular schwannomas tumor volume shrinkage and hearing improvement in the study was not strong; and that this may be due to the tumors shrinking spontaneously without treatment, which has been reported. Dr. Guntinas-Lichius also suggests the use of objective test methods such as brain-stem auditory evoked response. In reply, the NEJM NF2 study’s authors point out that the tumor shrinkage and hearing recovery they reported greatly exceeds what has been reported for spontaneous tumor shrinkage/hearing recovery. They also present rationale for the measures they used to monitor hearing changes, in part based on the fact that such a small population size was used for the study.
The second letter from Dr. Jian-Sheng Diao and colleagues, Fourth Military Medical University, China asks whether the shrinkage was due solely to ‘vascular normalization’ following drug treatment (a prominent known effect of bevacizumab) or whether it might also be due in part to tumor cells dying due to the direct effects of the drug. In responsethe NEJM NF2 study authors agree that both vascular ‘normalization’ and tumor cell death may have occurred in these tumors, and indeed, that if this is the case it might be partly responsible for the lack of tight correlation between tumor shrinkage and hearing recovery.
The publication of these letters in NEJM highlights the significance of this landmark NF2 study. It also shows that NF2 clinical trials are still early on the path. There are tremendous opportunities and challenges ahead; but always, a lot to be learned and progress to be made toward effective therapies for NF2.
* Plotkin SR, Stemmer-Rachamimov AO, Barker FG II, et al. Hearing improvement after bevacizumab in patients with neurofibromatosis type 2. N Engl J Med 2009;361:358-67.
** Guntinas-Lichius; Diao et al. Letters to the Editor N Engl J Med. 361;18 (October 29, 2009)
