To the Editor: In their letter to the editor, Budach et al.(Aug. 2 issue)1 report on two patients with squamous-cell carcinomaof the head and neck who had severe radiation dermatitis whilereceiving a combination of radiotherapy and cetuximab, a regimenfound to be superior to radiotherapy alone in our proof-of-conceptphase 3 trial.2 Severe radiation dermatitis can occur afterirradiation alone, but grade 4 dermatitis is rarely observed.In reviewing the case histories of the patients, Budach et al.note that Patient 1 had previously received etoposide-basedtherapy and Patient 2 had previously received a full courseof radiotherapy to the head and neck. Furthermore, both patientshad cirrhosis, and one had renal insufficiency. Whether thesecoexisting conditions altered the pharmacodynamics of cetuximaband, when confounded by the preexisting occult chemotherapy-or radiotherapy-induced dermal injury, predisposed the patientsto the development of more severe radiation dermatitis is difficultto assess. The absence of a cetuximab-induced maculopapularrash in Patient 1 might argue against any critical role of cetuximabin exacerbating radiation dermatitis in this patient.
James A. Bonner, M.D. University of Alabama at Birmingham Birmingham, AL 35233
Kian Ang, M.D., Ph.D. M.D. Anderson Cancer Center Houston, TX 77030
Dr. Bonner reports serving as a consultant for Bristol-MyersSquibb and Imclone Systems. Dr. Ang reports serving as a consultantfor Merck KGaA and ImClone Systems and having received grantsupport from ImClone Systems. No other potential conflict ofinterest relevant to this letter was reported.
References
Budach W, Bölke E, Homey B. Severe cutaneous reaction during radiation therapy with concurrent cetuximab. N Engl J Med 2007;357:514-515. [Free Full Text]
Bonner JA, Harari PM, Giralt J, et al. Radiotherapy plus cetuximab for squamous-cell carcinoma of the head and neck. N Engl J Med 2006;354:567-578. [Free Full Text]
The authors reply: We agree with Bonner and Ang that severeradiation dermatitis may occur after irradiation alone but thatgrade 4 lesions are rarely observed. Previous chemotherapy isunlikely to explain the severe reaction in our patients, sincePatient 1 had received her radiotherapy for breast cancer afterinduction chemotherapy without an enhanced skin reaction, andPatient 2 had not received chemotherapy at all. Both patientshad Child–Pugh class A cirrhosis. Pharmacokinetic studiesof cetuximab have shown that Child–Pugh class A cirrhosisdoes not modify serum levels of the drug or enhance cutaneousside effects.1,2 In the absence of marked proteinuria, negligiblerenal elimination of antibodies occurs. However, glomerularor tubular damage may markedly increase renal protein loss,which may include loss of immunoglobulins.3,4 Hence, renal insufficiencywith polyuria and proteinuria, as observed in Patient 1, wouldbe more likely to result in a loss of antibodies than in antibodyretention. We believe these findings argue for a causal relationshipbetween this treatment protocol and the observed cutaneous sideeffects, but more data are needed to help determine how oftenand in what clinical situations this complication may occur.
Wilfried Budach, M.D. Edwin Bölke, M.D. Bernhard Homey,M.D. University of Düsseldorf D-40225 Düsseldorf, Germany wilfried.budach{at}uni-duesseldorf.de
Since publication of the letter, Dr. Homey reports receivingresearch funding from Roche. No other potential conflict ofinterest relevant to this letter was reported.
References
Fracasso PM, Burris H III, Arquette MA, et al. A phase 1 escalating single-dose and weekly fixed-dose study of cetuximab: pharmacokinetic and pharmacodynamic rationale for dosing. Clin Cancer Res 2007;13:986-993. [Free Full Text]
Zhu AX, Stuart K, Blaszkowsky LS, et al. Phase 2 study of cetuximab in patients with advanced hepatocellular carcinoma. Cancer 2007;110:581-589. [CrossRef][Web of Science][Medline]
Bakoush O, Torffvit O, Rippe B, Tencer J. High proteinuria selectivity index based upon IgM is a strong predictor of poor renal survival in glomerular diseases. Nephrol Dial Transplant 2001;16:1357-1363. [Free Full Text]
Branten AJ, du Buf-Vereijken PW, Klasen IS, et al. Urinary excretion of beta2-microglobulin and IgG predict prognosis in idiopathic membranous nephropathy: a validation study. J Am Soc Nephrol 2005;16:169-174. [Free Full Text]
Jatoi, A., Nguyen, P. L.
(2008). Do Patients Die from Rashes from Epidermal Growth Factor Receptor Inhibitors? A Systematic Review to Help Counsel Patients About Holding Therapy. The Oncologist
13: 1201-1204
[Abstract][Full Text]
Previous
