1. J Clin Oncol 28:1351-1357. R2 소예리 / Prof. 이재진

2. INTRODUCTION EGFR is overexpressed in 70-80% of pts with advanced colorectal cancer EGFR dysregulation: decreased survival and poor prognosis => use of EGFR inhibitors (EGFRIs) dermatologic toxicities in more than 90% of patients; papulopustular rash, xerosis, pruritus, and paronychia randomized, phase II study Pre-emptive skin toxicity therapy VS Reactive treatment To evaluate the effect of comprehensive skin toxicity Panitumumab combined with Irinotecan or FOLFIRI (leucovorin, fluorouracil, and irinotecan)

3. PATIENTS AND METHODS Patients, Study Design and Treatment Schedule >=18 years old, ECOG PS 0 or 1, adequate hematologic,renal,metabolic,hepatic function. No prior irinotecan treatment or anti-EGFR therapy or vaccine treatment for mCRC no incidence of pul. embolism, DVT, or any other significant thromboembolic event within 8 wks

4. Study Objectives 1) Estimate the difference in incidence >=grade 2 skin toxicities pre-emptive and reactive skin treatment groups during the 6-week skin treatment period. 2) Assessment of the incidence rates of skin toxicities during the 6-week skin treatment period Assessment of the efficacy and safety of panitumumab given concomitantly with second-line irinotecan chemotherapy

5. RESULTS Patients

6. Primary End Point < < <

7. Antitumor Efficacy Safety <

8. QOL DLQI(Dermatology Life Quality Index indicated); less impaired in pre-emptive group Mean DLQI score change from baseline to week 3 pre-emptive (44 [96%] of 46 patients): 1.3 points reactive groups (42 [95%] of 44 patients): 4.2 points

9. DISCUSSION 4 major alterations occur in the skin of pts treated with EGFRIs: - follicular and interfollicular inflammation - bacterial super infection - dry skin - sensitivity to ultraviolet radiation topical corticosteroid hydrocortisone 1%; cutaneous inflammation and pruritus semisynthetic tetracycline analog doxycycline; anti-inflammatory inhibition of lymphocyte proliferation, neutrophil migration, and interleukin-6 synthesis Moisturizer Sunscreen

10. significant reduction of approximately50% in the development of grade 2 skin toxicities, lower rates of grade 2 and grade 3 toxicities non-skin toxicities (diarrhea, dehydration, neutropenia); also reduced in the pre-emptive arm  EGFRI or chemotherapy induced diarrhea; - inflammatory or infectious component - potentially improved with the use of doxycycline (the only systemic agent administered)

11. well-established correlation btw rash and clinical outcome  antitoxicity interventions do not impact antitumor activity of EGFRIs. Partial response and progression-free survival were numerically higher in the pre-emptive arm, though none of the observed differences were statistically significant. Further studies are warranted to explore these potential differences.

12. CONCLUSION The pre-emptive skin treatment regimen was well tolerated. The incidence of specific >=grade 2 skin toxicities during the 6-week skin treatment period; reduced > 50% in the pre-emptive group compared with the reactive group. less QOL impairment than patients in the reactive group.