Efficacy and skin toxicity management with cetuximab in metastatic colorectal cancer: outcomes from an oncologic/dermatologic cooperation.

PURPOSE: The aim of this study was to investigate the efficacy of the combination of irinotecan/cetuximab and to plan related skin toxicity management with an oncologic/dermatologic team. PATIENTS AND METHODS: Thirty-four patients with epidermal growth factor receptor (EGFR)-expressing metastatic colorectal cancer received cetuximab 400 mg/m2 as an initial dose and 250 mg/m2 weekly thereafter. In addition, patients received irinotecan 180 mg/m2 every 2 weeks. RESULTS: Thirty-two patients were evaluated for response rate (RR) and skin toxicity to establish the best management. In our study, the responses observed with cetuximab treatment were complete response in 1 patient (3%), partial response in 11 patients (34%), disease stabilization in 6 patients (19%), and progressive disease in 14 patients (44%). Of 34 patients evaluable for cutaneous toxicity, 10 patients (29%) presented with grade 1 eruption, 13 (38%) with grade 2 eruption, and 4 (12%) with grade 3 eruption. Allergic reactions such as flushing and urticaria (grade 2) were seen in 2 patients (6%). CONCLUSION: Cutaneous reactions consisted of follicular rash, xerosis, painful fissures in palms and soles, alterations in hair growth, and mucositis. In the majority of patients (80%-90%), the worst recorded skin effects were mild (grade 1) to moderate (grade 2). The incidence of severe cases (grade 3) was approximately 15%. All dermatologic effects were reversible and generally without sequelae within 4 weeks after treatment discontinuation. We observed significant correlations between degree of cutaneous toxicity and increased RR. Correct identification and treatment by oncologic/dermatologic cooperation of EGFR cutaneous side effects help to improve quality of life.

Specific detection of cytokeratin 20-positive cells in blood of colorectal and breast cancer patients by a high sensitivity real-time reverse transcriptase-polymerase chain reaction method.

A real-time reverse transcriptase-polymerase chain reaction (RT-PCR) method for detection of cytokeratin 20-positive cells in blood characterized by two novel features was developed and tested on 99 patients with colorectal cancer, 110 with breast cancer, and 150 healthy subjects. To optimize the specificity and sensitivity of the method, two novel features were used. First, a primer overlapping two adjacent exons was generated to inhibit nonspecific amplification both in healthy donors and cancer patients; second, a non-end-point first-round amplification was used to increase sensitivity. The number of first-round cycles was chosen to reach the highest level of sensitivity while conserving quantitative characteristics. PCR efficiency increased from 88.9% in single-round RT-PCR to 99.0% in nested real-time RT-PCR. To establish sensitivity and specificity of the method, HT29 cells were serially diluted with normal blood. Detection limit improved from 100 HT29 cells (single-round RT-PCR) to 1 to 10 cells (nested real-time RT-PCR) per 3 ml of whole blood. None of the healthy subjects was positive, whereas 22 and 29% of all colorectal and breast cancer patients, respectively, had cytokeratin 20 cell equivalents in blood. The association between cytokeratin 20 cell equivalents and metastasis was statistically significant for breast (P = 0.026) but not colorectal cancer patients (P = 0.361). Negativity of all 150 healthy controls examined confers diagnostic potential to the method.