This amazing picture was featured at The Philippine Daily Inquirer (Sat, Aug 04, 2007)---
"BEAUTY AFTER RUIN. More than 16 years after its destructive eruption in 1991, Mount Pinatubo now offers this breathtaking crater-lake at its summit. INQUIRER/TONETTE T. OREJAS"
I also presented on the "Differences between polarized light dermoscopy and immersion contact dermoscopy for the evaluation of skin lesions" at the Free Communications Session at the Congress of the International Dermoscopy Society (Naples, Italy). I presented on behalf of co-investigators Drs. Benvenuto-Andrade C, Dusza SW, Agero AL, Scope A, Rajadhyaksha M, Halpern AC and Marghoob AA. This paper has since been published at the Archives of Dermatology (see Publications link).
I attach below the abstract:
OBJECTIVE: To evaluate dermoscopic features and patterns of skin lesions by using
conventional and polarized light dermoscopy (PD).
DESIGN: Observational study.
SETTING: Dermatology clinic at Memorial Sloan-Kettering Cancer Center.
PATIENTS: Ninety patients with skin lesions.
INTERVENTIONS: Skin lesions were imaged via conventional nonpolarized light contact dermoscopy (NPD), polarized light contact dermoscopy (PCD), and polarized light noncontact dermoscopy (PNCD).
MAIN OUTCOME MEASURES: The images from the 3 modalities were evaluated by 3 dermoscopists for colors, structures, and patterns. Level of agreement between modalities was assessed by percentage agreement and the kappa statistic. Qualitative differences between modalities were also assessed.
RESULTS: Ninety lesions comprising 55 melanocytic and 35 nonmelanocytic lesions were reviewed. There was excellent agreement for overall dermoscopic patterns between modalities, with kappa values ranging from 0.88 to 1.00. There was moderate to excellent agreement for most dermoscopic colors, with the exception of blue-white veil and pink (red) color. Most dermoscopic structures had fair to perfect agreement, with the exception of milialike cysts. Qualitative assessment suggested that melanin appeared darker and blue nevi had more shades of blue on PD compared with NPD images; vessels and red areas were better visualized with PD, suggesting that PD may be helpful in identifying malignancies; milialike cysts and comedolike openings were better visualized with NPD, suggesting that NPD is more helpful for identification of seborrheic keratosis; peppering, lighter colors, and blue-white areas were more evident under NPD, facilitating recognition of regression areas; and shiny-white streaks, possibly representing fibrosis, were seen more clearly under PD.
CONCLUSIONS: The capabilities of NPD, PCD, and PNCD are not equivalent, but complementary. Further studies are needed to evaluate the effect of these differences on clinical diagnosis.
(Picture taken at the ruins of Pompeii, with Vesuvius in the background)
I was fortunate to be chosen to present at the Free Communications Session at the Congress of the International Dermoscopy Society (Naples, Italy). I presented on behalf of co-investigators Drs. S. Taliercio, C. Salaro, S. Dusza, P. Chu and A. Marghoob on our paper on the "Conventional and polarized dermoscopy features of dermatofibroma". Basically, what we found from the study was that there are differences with the resulting image when using conventional versus polarized dermoscopy. These differences may become significant in that while many dermoscopy courses and atlases feature photos of lesions taken with conventional dermoscopy, many neophyte dermoscopists are starting out with polarized dermoscopes.
This is the abstract of the talk, which has since also been published in the Archives of Dermatology (see Publications link):
OBJECTIVE: To evaluate dermoscopic features and patterns of dermatofibromas using conventional and polarized light dermoscopy.
DESIGN: Dermatofibromas were imaged using conventional nonpolarized contact dermoscopy (NPD), polarized contact dermoscopy (PCD), and polarized noncontact dermoscopy, followed by evaluation and comparison of dermoscopic features of the lesions.
SETTING: Dermatology clinic specializing in pigmented lesions. Patients Fifty patients with dermatofibromas.
RESULTS: The most common features of dermatofibromas observed with NPD and PCD were central white scarlike patches (37 [74%] and 42 [84%], respectively), brown globulelike structures (21 [42%] and 22 [44%]), vascular structures (24 [48%] and 22 [44%]), and a peripheral fine pigmented network (36 [72%] for both). A newly described feature observed with PCD was a central white patch characterized by shiny white streaks. With polarized noncontact dermoscopy, the most characteristic feature was a central pink hue or "vascular blush" (44 [88%]) and visibility of blood vessels (41 [82%]). The most common pattern identified with NPD and PCD was the combination of a peripheral pigmented network and a central white patch in 28 (56%) and 31 (62%) of lesions, respectively. With polarized noncontact dermoscopy, the most common pattern was a central pink hue with a peripheral pigmented network (23 [46%]). There was good to excellent agreement when comparing NPD with PCD images, but there was a variable level of agreement when polarized noncontact dermoscopy images were compared with NPD and PCD images.
CONCLUSIONS: Conventional and polarized light dermoscopy are not equivalent but may be complementary. This study highlights some salient differences. We were able to identify new dermoscopic features and patterns not previously described with conventional dermoscopy. These new criteria can aid in the diagnosis of dermatofibroma.
(At the meeting with Dr. Anne Amon and Dr. Vangie Handog, dermatologists from Manila)
ReCell® is a novel single-use medical device developed as an 'off the shelf' kit for harvesting autologous skin cells taken from a thin split thickness biopsy. The process provides an immediate cell population composed of keratinocytes, melanocytes, fibroblasts and Langerhans cells harvested from the epidermal-dermal junction for delivery onto the wound surface in order to promote effective wound healing. ReCell® has been used to treat smaller wounds such as small burns and scalds, donor sites, glabrous injuries, congenital nevi, hypopigmentation, chronic wounds and prophylactically in cosmetic rejuvenation procedures. The procedure is simple. Once processed, the cell suspension is available for immediate use and can cover a wound many times the area of the donor biopsy. As the ReCell® device enables cell processing at the site of treatment without the use of specialised laboratory staff, the process is both cost and time efficient.
Our interest in ReCell® stems from its ability to enable melanocyte repopulation which may result in the reintroduction of pigmentation into hypopigmented skin such as in hypopigmented scars, iatrogenic hypopigmentation and Vitiligo. At St George Hospital (NSW, Australia), we are currently conducting a randomized double blind study comparing ReCell® versus minigrafting for patients with stable vitiligo who have previously failed medical treatment. My co-investigators include Dr. John Le Guay and Dr. Richard Wittal of the Skin & Cancer Foundation and A/Prof Dedee Murrell and Dr. Linda Martin (St. George Hospital). We have currently recruited 14 out of a target of 24 patients, and the study is still open for interested patients. The entire procedure is performed by just myself and our trial nurse (Lesley Rhodes SRN), as the whole process does not require specialized laboratory staff. Patients also find it convenient as the on-site processing allows immediate application.
I was fortunate to be chosen as one of 20 presenters at the Residents & Fellows Symposium at the Annual Meeting of the American Academy of Dermatology (Washington DC, 2007). My presentation was on "PROPHYLAXIS WITH SYSTEMIC MINOCYCLINE AND TOPICAL TAZAROTENE (A RETINOID) FOR THE CETUXIMAB ASSOCIATED ACNE-LIKE ERUPTION". I presented on behalf of co-investigators Drs. Alon Scope, Stephen W. Dusza, Patricia L. Myskowski, Jocelyn Lieb, Leonard Saltz, Nancy E. Kemeny and Allan C. Halpern.
Cetuximab, an epidermal growth factor receptor inhibitor, is a biologically targeted agent that has been approved by the FDA for treatment of chemotherapy resistant/intolerant patients with metastatic colorectal carcinoma and unresectable squamous cell cancer of the head and neck. Cetuximab is associated with a characteristic dose-related follicular-pustular (acne-like) eruption affecting up to 90% of patients that is severe or dose-limiting in 10-20% of patients. Presently, there are no specific evidence-based treatments available for the inflammatory eruption. Patients are typically treated with dose modification, and empirically with drying agents, retinoids, steroids and antibiotics, but without evidence of consistent benefit.
This double-blinded randomized placebo-controlled single-center study aimed to assess the utility of topical tazarotene, oral minocycline or combination therapy for prevention of cetuximab-related rash. These agents were chosen based on anecdotal reports of their efficacy in cetuximab-related rash and their potential impact on follicular integrity and inflammation.
Patients with a diagnosis of colorectal cancer initiating cetuximab therapy were randomized to receive half-face twice a day topical therapy with tazarotene cream 0.01% and either oral minocycline (100mg daily) or oral placebo for two months. The primary endpoint in the study was the difference in total face lesion counts between minocycline- and placebo-treated patients at week 8. Secondary endpoints included the difference in total face lesion counts between minocycline- and placebo-treated patients at weeks 1-4 and difference in lesion counts between tazarotene-treated and observation sides of the face at weeks 1-8.
Forty eight eligible patients were randomly assigned to minocycline (n=24) or placebo (n=24). Median age was 44 years (range 38-83), with M: F (2:1) and 84% were white non-Hispanic. There was no significant difference between total facial lesions counts at week 8 between these groups. However, lesion counts were significantly attenuated in patients on minocycline at weeks 1-4. In 4 patients in the placebo- and in none in the minocycline-arm, cetuximab treatment was interrupted due to grade 3 skin adverse events. There was limited clinical benefit to tazarotene application.
We concluded that prophylaxis with minocycline was effective in decreasing severity of the acneiform rash during the first weeks of cetuximab therapy, suggesting that short-term minocycline prophylaxis for patients starting on cetuximab is beneficial.
(Reunion of the MSKCC team at the AAD meeting in Washington DC. Top row, L-R, Ms Daphne Demas, Dr. Philip Spencer, Dr. Cristiane Benvenuto-Andarade, me, Dr. Patricia Myskowski, Dr. Alon Scope, Steve Dusza, Bottom row, L-R, Jules Lipoff, Dr. Jason Chen, Dr. Allan Halpern, Dr. Jocelyn Lieb)
I was very fortunate to have been chosen to present at the Residents & Fellows Symposium at the American Academy of Dermatology Meeting (San Francisco, 2006). This was also my first time to present at the Fellows Symposium.
I presented on "Reflectance Confocal Microscopy of Pigmented Basal Cell Carcinoma" on behalf of co-investigators Drs. Busam KJ, Benvenuto-Andrade C, Scope A, Gill M, Marghoob AA, González S and Halpern AC, with very good feedback from the audience who were impressed with the quality of the images taken with the confocal microscope. I had worked on the imaging of several pigmented basal cell cancers as part of my fellowship at Memorial Sloan-Kettering Cancer Center, and summarized the findings in this presentation. Confocal microscopy was able to demonstrate tumor aggregations demonstrating palisading cells, cord-like structures and nodules with irregular borders and variable brightness; these represented nests of pigmented basaloid tumor cells on histopathology, and blue-gray ovoid areas on dermoscopy. These tumor nests were associated with bright dendritic structures, identified histologically as either melanocytes or Langerhans cells, together with numerous bright oval to stellate-shaped structures with indistinct borders representing melanophages, and with highly refractile granules of melanin. We have since published on this topic in the Journal of the American Academy of Dermatology (see Publications link).
This is the abstract for this presentation:
BACKGROUND: Reflectance confocal microscopy (RCM) is a high-resolution imaging tool for in vivo noninvasive evaluation of skin lesions.
OBJECTIVE: We sought to describe the relevant RCM features for pigmented basal cell carcinoma (BCC).
METHODS: Pigmented skin lesions with a differential diagnosis of pigmented BCC were imaged using dermoscopy and RCM, followed by excision for histologic analysis.
RESULTS: RCM demonstrated aggregations of tightly packed cells with palisading, forming cordlike structures and nodules with irregular borders and variable brightness; these represented nests of pigmented basaloid tumor cells on histopathology, and blue-gray ovoid areas on dermoscopy. These tumor nests were associated with bright dendritic structures, identified histologically as either melanocytes or Langerhans cells, together with numerous bright oval to stellate-shaped structures with indistinct borders representing melanophages, and with highly refractile granules of melanin.
LIMITATIONS: The pigmented BCCs imaged in this study were predominantly nodular; a different set or additional criteria may be necessary for detection of infiltrative and metatypical BCCs.
CONCLUSION: RCM may permit in vivo diagnosis of pigmented BCC.
This was my first time to participate as a faculty at a two hour forum at the American Academy of Dermatology Annual Meeting (San Franciscio, 2006). They spelled my name wrong however in the program (!!!)
My thanks to my two mentors, Dr. Allan C. Halpern (chief of the Dermatology Service at Memorial Sloan-Kettering Cancer Center, NY, USA) and Dr. Patricia L. Myskowski (also a consultant at MSKCC). They understood how nervous I was for this session, and gave me lots of support! It was very well attended as many dermatologists are dealing more and more with patients suffering from these adverse events as the use of anti-EGFR cancer treatment becomes more widespread.
This is the abstract for this session. We have also published on this topic at the Journal of the American Academy of Dermatology (see Publications link).
SKIN EFFECTS OF BIOLOGICALLY TARGETED CANCER THERAPIES
Anna Liza C Agero MD, Allan C. Halpern MD, Patricia Myskowski MD
SHORT ABSTRACT
One of the recent exciting advances in medicine has been the development of novel biologically targeted agents that interfere with specific molecular pathways affecting the evolution of cancer. Some examples of these new class of anti-neoplastic agents include monoclonal antibodies and inhibitors of intracellular signaling pathways (receptor and tyrosine kinase inhibitors). A number of unique and dramatic dermatologic side-effects have been associated with the use of these biotherapeutic agents. This forum will summarize the spectrum of cutaneous reactions to some of these agents, focusing on the epidermal growth factor receptor (EGFR) inhibitors and some multi-targeted kinase inhibitors, based primarily on our experience at
LONG ABSTRACT
One of the recent exciting advances in medicine has been the development of novel biologically targeted agents that interfere with specific molecular pathways affecting the evolution of cancer. Some examples of these new class of anti-neoplastic agents include monoclonal antibodies and inhibitors of intracellular signaling pathways (receptor and tyrosine kinase inhibitors). This forum summarizes the spectrum of cutaneous reactions to some of these agents, focusing on the epidermal growth factor receptor (EGFR) inhibitors and some multi-targeted kinase inhibitors, based primarily on our experience at
Epidermal growth factor receptor (EGFR) inhibitors are members of this new class of anti-neoplastic agents. These agents were developed for therapeutic blockade of the epidermal growth factor receptor function, which has been shown to play a significant role in signal transduction pathways affecting cancer growth and spread. These targeted therapies have the potential of offering efficacy without the major toxicities associated with conventional chemotherapeutic agents. The EGFR-targeted antibody Cetuximab, and the small tyrosine kinase inhibitors Erlotinib and Gefitinib have recently received approval from the FDA for treatment of patients with colorectal and non-small cell lung cancer refractory or intolerant to chemotherapy.1,2 In particular, Erlotinib therapy has been shown to improve survival in patients with advanced or refractory non-small cell lung cancer compared to placebo.3 Treatment with Gefitinib has also demonstrated clinically meaningful improvements in disease-related symptoms and health related quality of life in patients with advanced non-small cell lung cancer. Erlotinib treatment is another anti-EGFR agent that has also shown improvement in patients’ health-related quality of life.4 Anti-EGFR therapies are currently being tested in other disease settings, and as their use become more prevalent, their side-effects profiles become clinically significant.
Anti-EGFR therapy is commonly associated with unique and dramatic dermatologic side-effects that appear to be secondary to inhibition of specific roles EGFR plays in skin biology. The most commonly encountered toxicity in patients is a characteristic skin rash that occurs in up to 85% of patients, while nail, hair and mucosal changes appear less frequently.5 The skin rash is characterized by sterile suppurative follicular lesions6,7, and is commonly described as “acne-like” and “acneiform.”3 The face, upper chest and back are the most frequently affected areas.5 The follicular rash often commences between days ten and fourteen of therapy,7,8 and is maximal by weeks three to five.9 A dose-related reaction is also seen, with higher incidence and more severe rash noted at higher dose levels.7,10 The skin reaction is generally mild and well tolerated, usually accompanied only by minimal discomfort or pruritus,8,11-13 but may rarely be more severe and widespread.14 The rash is rarely dose-limiting, and in a number of studies, skin toxicity did not exceed Grade 2 in severity.15-17 However, there are cases wherein a patient was severely distressed by the cosmetic effects, and chose to withdraw from treatment although the rash was asymptomatic.14
Currently, there is no specific evidence-based treatment for the pustular-follicular rash caused by the anti-EGFR agents. Patients who develop mild to moderate skin toxicity are recommended to continue treatment without dose modification. When intervention is indicated, patients have been treated empirically with drying agents, retinoids, steroids and antibiotics.8 However, attempts at clinical prevention or improvement of the rash have not shown consistent benefit.6,18,19
Histopathology studies of the pustular-follicular lesions have revealed two major patterns of reactions: a moderate superficial dermal inflammatory cell infiltrate surrounding hyperkeratotic and ectatic follicular infundibula, particularly in the upper portion of the hair follicle, and a superficial neutrophilic suppurative folliculitis with associated rupture of epithelial lining.6,18,20 The exact mechanism for the ‘acne-like’ and folliculo-centricity of the rash is still not clear, though it is agreed that it is a consequence of inhibition of EGFR signaling on epidermal and adnexal epithelium. Several pre-clinical studies have shown an essential role for EGFR activation in keratinocyte proliferation with studies of EGFR-knockout mice showing skin and hair abnormalities.21
Significantly, occurrence of the rash has been linked to better clinical outcomes,22 such that studies investigating dose escalation of Erlotinib until occurrence of Grade 2 or maximally tolerated rash are underway in order to determine clinical benefit at the maximally tolerated dose.23,24 However, more data are needed to confirm a possible relationship between rash (and severity of rash) with clinical response.
Other changes associated with anti-EGFR therapy include painful nail paronychia characterized as a periungual granulation-type of paronychia 25 or friable pyogenic granuloma-like changes18, coupled with erythema, tenderness, swelling and fissuring of lateral nail folds and/or distal finger tufts.18,26,27 Paronychia often develops after 2-4 months of treatment,27 but with a much lower incidence (12%) than rash.26 Changes with hair growth have also been noted, with reports of curlier, finer and more brittle hair on the scalp and extremities, and slowed growth of beard hair.28,29 Extensive growth of both eyelashes and eyebrows have also been reported.30 Other dermatologic changes observed are skin dryness that develops after onset of rash, mild to moderate mucositis, and hypersensitivity reactions.5
Other biologically targeted therapies include the multi-targeted kinase inhibitors: Imatinib (inhibitor of platelet-derived growth factor (PDGF), stem cell factor (SCF), c-kit, and Bcr-Abl), BAY 43-9006/Sorafenib (inhibitor of Raf/MEK/ERK pathway, VEGFR-2 &3 , FLT-3, p38, PDGFR and c-kit) and SU11248/ Sunitinib (inhibitor of VEGFR-2, PDGFR, FLT3 TKr and c-kit).5 Imatinib is FDA approved for refractory chronic myeloid leukemia, BAY 43-9006 for advanced renal cell carcinoma, and SU11248 is undergoing clinical trials as a treatment for gastrointestinal stromal tumor and metastatic renal cell carcinoma (www.fda.gov).
Treatment with Imatinib has been associated with a wide range of skin reactions, with 30-40% incidence of non-specific self-limited skin rash, and rare reports of more severe drug reactions such as vasculitis, Stevens-Johnson Syndrome, toxic epidermal necrolysis and acute generalized exanthematous pustulosis.5
Changes in skin and hair pigmentation have been observed during treatment with Imatinib and SU11248, with reports of dose-dependent and reversible local and diffused skin hypo- or depigmentation and variable reports of hair depigmentation and/or repigmentation.5 Pigmentation changes may be attributed to selectivity to the C-kit receptor which plays a regulatory role in melanocyte development.
Subungual splinter hemorrhages have been a common side effect (30-60% of patients) of patients taking SU11248 and BAY 439006. These have not been associated with thrombotic and embolic events, and may be secondary to inhibition of VEGFR.5
As use of these targeted agents become more prevalent, it is important that dermatologists be able to properly diagnose these side-effects, and differentiate them from other skin disorders. These dermatologic reactions may be relatively common and generally mild, but may also cause clinical distress to the patient.
REFERENCES
1. Kim ES, Khuri FR, Herbst RS. Epidermal growth factor receptor biology (IMC-C225). Curr Opin Oncol. 2001;13:506-513.
2. De Bono JS, Rowinsky EK. The ErbB receptor family: a therapeutic target for cancer. Trends Mol Med. 2002;8:S19-26.
3. Perez-Soler R, Delord JP, Halpern A, et al. HER1/EGFR inhibitor-associated rash: future directions for management and investigation outcomes from the HER1/EGFR inhibitor rash management forum. Oncologist. 2005;10:345-356.
4. Fallowfield LJ, Harper P. Health-related quality of life in patients undergoing drug therapy for advanced non-small-cell lung cancer. Lung Cancer. 2005;48:365-377.
5. Robert C, Soria JC, Spatz A, et al. Cutaneous side-effects of kinase inhibitors and blocking antibodies. Lancet Oncol. 2005;6:491-500.
6. Cohen R, Falcey J, Paulter V, Fetzer K, Waksal H. Safety profile of the monoclonal antibody (MoAb) IMC-C225, an anti-epidermal growth factor receptor (EGFr) used in the treatment of EGFr-positive tumors. Proc Am Soc Clin Oncol. 2000;19:474a Abs. 1862.
7. Ranson M, Hammond LA, Ferry D, et al. ZD1839, a selective oral epidermal growth factor receptor-tyrosine kinase inhibitor, is well tolerated and active in patients with solid, malignant tumors: results of a phase I trial. J Clin Oncol. 2002;20:2240-2250.
8. Perez-Soler R, Chachoua A, Hammond LA, et al. Determinants of tumor response and survival with erlotinib in patients with non--small-cell lung cancer. J Clin Oncol. 2004;22:3238-3247.
9. Rowinsky EK, Schwartz GH, Gollob JA, et al. Safety, pharmacokinetics, and activity of ABX-EGF, a fully human anti-epidermal growth factor receptor monoclonal antibody in patients with metastatic renal cell cancer. J Clin Oncol. 2004;22:3003-3015.
10. Herbst RS, Maddox AM, Rothenberg ML, et al. Selective oral epidermal growth factor receptor tyrosine kinase inhibitor ZD1839 is generally well-tolerated and has activity in non-small-cell lung cancer and other solid tumors: results of a phase I trial. J Clin Oncol. 2002;20:3815-3825.
11. Walon L, Gilbeau C, Lachapelle JM. Acneiform eruptions induced by cetuximab. Ann Dermatol Venereol. 2003;130:443-446.
12. Schwartz G, Dutcher JP, Vogelzang NJ, et al. Phase 2 clinical trial evaluating the safety and effectiveness of ABX-EGF in renal cell cancer (RCC). Proc Am Soc Clin Oncol. 2002;21:24 Abs. 91.
13. Albanell J, Rojo F, Averbuch S, et al. Pharmacodynamic studies of the epidermal growth factor receptor inhibitor ZD1839 in skin from cancer patients: histopathologic and molecular consequences of receptor inhibition. J Clin Oncol. 2002;20:110-124.
14. Yamamoto DS, Viale PH, Zhao G. Severe acneiform rash. Clin J Oncol Nurs. 2004;8:654-656.
15. Kollmannsberger C, Schittenhelm M, Honecker F, et al. Epidermal growth factor receptor (EGFR) antibody EMD 72000 in combination with paclitaxel (P) in patients (pts) with EGFR-positive advanced non-small cell lung cancer (NSCLC): A phase-I study. Proc Am Soc Clin Oncol. 2003;22:627 Abs. 25206.
16. Trarbach T, Beyer T, Schleucher N, et al. A randomized phase I study of the humanized anti-epidermal growth factor receptor (EGFR) monoclonal antibody EMD 72000 in subjects with advanced gastrointestinal cancers. Journal of Clinical Oncology, 2004 ASCO Annual Meeting Proceedings (Post-Meeting Edition). 2004;22:3018.
17. Herbst RS, LoRusso PM, Purdom M, Ward D. Dermatologic side effects associated with gefitinib therapy: clinical experience and management. Clin Lung Cancer. 2003;4:366-369.
18. Busam KJ, Capodieci P, Motzer R, Kiehn T, Phelan D, Halpern AC. Cutaneous side-effects in cancer patients treated with the antiepidermal growth factor receptor antibody C225. Br J Dermatol. 2001;144:1169-1176.
19. Hidalgo M, Siu LL, Nemunaitis J, et al. Phase I and pharmacologic study of OSI-774, an epidermal growth factor receptor tyrosine kinase inhibitor, in patients with advanced solid malignancies. J Clin Oncol. 2001;19:3267-3279.
20. Jacot W, Bessis D, Jorda E, et al. Acneiform eruption induced by epidermal growth factor receptor inhibitors in patients with solid tumours. Br J Dermatol. 2004;151:238-241.
21. Jost M, Kari C, Rodeck U. The EGF receptor - an essential regulator of multiple epidermal functions. Eur J Dermatol. 2000;10:505-510.
22. Saltz LB, Kies MS, Abbruzzese JL, Azarnia N, Needle M. The presence and intensity of the cetuximab-induced acne-like rash predicts increased survival in studies across multiple malignancies. Proc Am Soc Clin Oncol. 2003;22:204 Abs. 817.
23. Brewer CJ, Suh JH, Stevens GHJ, et al. Phase II trial of erlotinib with temozolomide and concurrent radiation therapy in patients with newly-diagnosed glioblastoma multiforme. Journal of Clinical Oncology, 2005 ASCO Annual Meeting Proceedings. 2005;23:16S Abs.1567.
24. Mita CA, Schwartz G, Mita MM, et al. A pilot, pharmacokinetic (PK), and pharmacodynamic (PD) study to determine the feasibility of intrapatient dose escalation to tolerable rash and the activity of maximal doses of erlotinib (E) in previously treated patients with advanced non-small cell lung cancer (NSCLC). Journal of Clinical Oncology, 2005 ASCO Annual Meeting Proceedings. 2005;23.
25. Boucher KW, Davidson K, Mirakhur B, Goldberg J, Heymann WR. Paronychia induced by cetuximab, an antiepidermal growth factor receptor antibody. J Am Acad Dermatol. 2002;47:632-633.
26. Saltz LB, Meropol NJ, Loehrer PJ, Sr., Needle MN, Kopit J, Mayer RJ. Phase II trial of cetuximab in patients with refractory colorectal cancer that expresses the epidermal growth factor receptor. J Clin Oncol. 2004;22:1201-1208.
27. Monti M, Mancini LL, Ferrari B, Rahal D, Santoro A. Complications of therapy and a diagnostic dilemma case. Case 2. Cutaneous toxicity induced by cetuximab. J Clin Oncol. 2003;21:4651-4653.
28. Van Doorn R, Kirtschig G, Scheffer E, Stoof TJ, Giaccone G. Follicular and epidermal alterations in patients treated with ZD1839 (Iressa), an inhibitor of the epidermal growth factor receptor. Br J Dermatol. 2002;147:598-601.
29. Cohen EE, Rosen F, Stadler WM, et al. Phase II trial of ZD1839 in recurrent or metastatic squamous cell carcinoma of the head and neck. J Clin Oncol. 2003;21:1980-1987.
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