Case report 1227 Skin rash secondary to bevacizumab in a patient with advanced colorectal cancer and relation to response Vladimir Gotlib a , Samer Khaled a , Igor Lapko b , Nataliya Mar c and Muhammad Wasif Saif d Bevacizumab (Avastin) in combination with intravenous 5-fluorouracil-based chemotherapy as first-line as well as second-line treatment of metastatic colorectal cancer improves survival. Although skin rash (type unspecified) has been described in some patients following infusion of bevacizumab, it is not a common toxicity of bevacizumab, while acneiform rash occurs in more than 90% of patients who receive cetuximab (Erbitux), the severity of which appears to be predictive of response. We report a patient with colorectal cancer who developed a rash secondary to bevacizumab that correlated with response. A 40-year-old patient with stage IV colorectal cancer received FOLFOX-4 and bevacizumab, which he tolerated very well except for a skin rash related to bevacizumab. The rash cleared every time bevacizumab was eliminated from the chemotherapy regimen. When use of bevacizumab was resumed, similar rash reappeared. Therefore, we believe that this observation of the rash emergence was linked to bevacizumab administration. The most common toxicities associated with bevacizumab include hypertension, hemorrhage, gastrointestinal perforation, arterial thromboembolism, wound healing and proteinuria. Exfoliative dermatitis and a nonspecific rash have been reported with bevacizumab. This case report, we believe, is the first report of a possible correlation between a rash and a positive drug response associated with bevacizumab, and may initiate further investigation of similar observation. Anti-Cancer Drugs 17:1227–1229  c 2006 Lippincott Williams & Wilkins. Anti-Cancer Drugs 2006, 17:1227–1229 Keywords: bevacizumab (Avastin), cetuximab (Erbitux), colorectal cancer, epidermal growth factor receptor, rash, vascular endothelial growth factor a The Brooklyn Hospital Center of Cornell Medical College, Brooklyn, New York, b Long Island Jewish Medical Center, New Hyde Park, New York, c New York University School of Medicine, New York and d Yale University School of Medicine, New Haven, Connecticut, USA. Correspondence to M.S. Saif, Division of Medical Oncology, Yale University School of Medicine, 333 Cedar Street, FMP 116, New Haven, CT 06520, USA. Tel: +1 203 737 1875; fax: +1 203 785 3738; e-mail: wasif.saif@yale.edu Received 8 May 2006 Accepted 30 June 2006 Introduction Bevacizumab (Avastin; Genentech, South San Francisco, California, USA) (BV), in combination with intravenous fluorouracil (FU)-based regimens, is an accepted stan- dard of care for the treatment of metastatic colorectal cancer (CRC) in the first-line setting. For instance, there was an improvement in response rates by 17% with FU/leucovorin (LV), 40% with FU/LV + BV 5/mg/kg and 24% with FU/LV + BV 10 mg/kg in one of the intial randomized phase II studies [1]. The ‘TREE-2’ trial was the first to combine BV with oxaliplatin-based regimens in the first-line treatment of CRC [2]. Patients were randomized to either BV + FOLFOX, bolus FU with oxaliplatin or capecitabine and oxaliplatin. The results indicated that the response rates among the groups were 49, 34 and 43%, respectively. Overall grade 3/4 toxicities with first-line BV + oxaliplatin-based chemotherapy were less than reported for irinotecan, bolus fluorouracil and leucovorin [2,3]. The BOND-2 trial is a randomized phase II trial of cetuximab and BV vs. cetuximab, BV and irinotecan [4]. The results showed an improvement in the time taken for progression and response rates compared with historical data from the BOND-1 trial. This study proved that combining biological agents is feasible and safe, with no unexpected toxicities. Trials of BV in CRC have identified proteinuria (all grades 1–28%), hypertension (all grades 3–25%), wound healing complications (1–2%), hemorrhage (2–9.3%), arterial thromboembolism (0–3.8%) and gastrointestinal perfora- tion (1.5%) as BV-associated adverse effects. Skin rash (type unspecified) has been described in some patients following BV infusion [5–7]. On the other hand, acnei- form rash occurs in more than 90% patients who receive cetuximab (Erbitux), the severity of which appears to be predictive of response [8]. We report a patient with CRC who developed a rash secondary to BV. Case report A 40-year-old male nurse with unremarkable past medical history presented with acute rectal bleeding. Colono- scopy revealed a sigmoid mass approximately 22 cm from the anal verge, while biopsy revealed a well-differentiated adenocarcinoma. A positron emission tomography/com- puted tomography (CT) scan taken before surgery was negative. The patient underwent a left hemicolectomy during which four liver lesions – all mapping to the right lobe – were discovered. An evaluation for possible liver resection via a liver CT-portogram, however, yielded multiple (more than 10) lesions in both lobes (Fig. 1), 0959-4973  c 2006 Lippincott Williams & Wilkins Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.