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Temozolomide: Too Early for Definitive Conclusions

Mayo Clinic, Rochester, MN

To the Editor: In the February 15, 2003, issue of the Journal of Clinical Oncology, Quinn et al¹ reported a phase II trial of temozolomide in patients with progressive low-grade glioma. The authors claim that radiation therapy results in substantial neurologic dysfunction in low-grade glioma patients. In our experience, radiation-induced neurologic toxicity has not been a major issue.^2,3 Moreover, in their review of radiation induced toxicities, one of the two provided references is a series of patients who had received significant overdoses from an improperly calibrated cobalt unit⁴. Using this reference to persuade one not to proceed with radiation therapy would be akin to reviewing the toxicities of a series of patients accidentally overtreated with chemotherapy as an argument against the use of chemotherapy.

In their discussion, the authors state radiation has "equally devastating effects in adults as it does in children." Clinical experience or a quick review of the literature will absolutely refute this statement. Although devastating neurocognitive deterioration is not uncommon after cranial radiation for pediatric patients^5,6 (especially children younger than 4 years), in adults who have undergone focal, conventionally fractionated radiotherapy using modern techniques, it is quite rare. A number of studies have performed extensive neuropsychological testing of adult patients with low-grade gliomas after radiotherapy and have not found significant neurocognitive deficits when compared to either baseline or to a cohort of patients with low-grade gliomas not treated with radiotherapy.^3,7–9

Clearly, there is mounting evidence that chemotherapy may be effective for progressive low-grade glioma. However, we agree with the authors that the follow-up on this trial is still very short (11.2 months) and that further prospective trials should be completed before chemotherapy is considered the standard of treatment (instead of radiotherapy) as first-line treatment for patients with progressive low-grade glioma.

AUTHORS’ DISCLOSURES OF POTENTIAL CONFLICTS OF INTEREST

The authors indicated no potential conflicts of interest.

REFERENCES

1. Quinn JA, Reardon DA, Friedman AH, et al: Phase II trial of temozolomide in patients with progressive low-grade glioma. J Clin Oncol 21:646–651, 2003[Abstract/Free Full Text]

2. Brown PD, Buckner JC, Brown CA, et al: The effects of radiation on cognitive function in patients with low-grade glioma. Proc Am Soc Clin Oncol 20:58, 2001 (abstr 229)

3. Hammack JE, Shaw EG, Ivnik RJ, et al: Neurocognitive function in patients receiving radiation therapy for supratentorial low-grade glioma: A North Central Cancer Treatment Group prospective study. Proc Am Soc Clin Oncol 14:151, 1995 (abstr 299)

4. Cohen L, Schultheiss TE, Kennaugh RC: A radiation overdose incident: Initial data. Int J Radiat Oncol Bio Phys 33:217–224, 1995[CrossRef][Medline]

5. Cappelli C, Raquin M, Pierre-Kan A: Long term follow-up of 69 patients treated for optic pathway tumours before the chemotherapy era. Arch Dis Child 79:334–338, 1998[Abstract/Free Full Text]

6. Chadderton RD, West CG, Schuller S, et al: Radiotherapy in the treatment of low-grade astrocytomas, II: The physical and cognitive sequelae. Childs Nervous System 11:443–448, 1995[CrossRef][Medline]

7. Vigliani MC, Sichez N, Poisson M, et al: A prospective study of cognitive functions following conventional radiotherapy for supratentorial gliomas in young adults: 4-year results. Int J Radiat Oncol Biol Phys 35:527–533, 1996[CrossRef][Medline]

8. Gregor A, Cull A, Traynor E, et al: Neuropsychometric evaluation of long-term survivors of adult brain tumours: Relationship with tumour and treatment parameters. Radiother Oncol 41:55–59, 1996[Medline]

9. Klein M, Heimans JJ, Aaronson NK, et al: Effect of radiotherapy and other treatment-related factors on mid-term to long-term cognitive sequelae in low-grade gliomas: A comparative study. Lancet 360:1361–1368, 2002[CrossRef][Medline]

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This Article Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Services Email this article to a colleague Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Save to my personal folders Download to citation manager Rights & Permissions Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Brown, P. Articles by Buckner, J. Search for Related Content PubMed PubMed Citation Articles by Brown, P. Articles by Buckner, J. Social Bookmarking                            What's this?