Pre-Emptive Low-Dose Doxycycline During Anti-Egfr Treatment: A Phase Ii Study

Introduction: Over 80% of colorectal cancer (CRC) patients treated with anti-EGFR antibodies (cetuximab or panitumumab) suffer from various types of skin toxicity – including acne-like rash, xerosis, paronychia or telangiectasia. The prospective clinical trial phase II (STEPP) proved that the primary prophylaxis with oral doxycycline (200 mg daily), topical steroids and sun blockers was efficacious. To further test the efficacy of systemic doxycycline we planned a single arm phase II prospective study of lower dose doxycycline (100 mg daily orally) in prevention of anti-EGFR skin toxicity in CRC patients.Methods: Eligibility included CRC qualified for treatment with panitumumab or cetuximab, WHO status of 0-2, age ≥18 years, lack of contraindications for using doxycycline and informed consent. The primary outcome was a number of patients with skin toxicity ≥ 2 grade during 8 weeks observation. The secondary outcome measures were: occurrence of skin toxicities by type, compliance to protocol, reason for discontinuing the anti-EGFRs and doxycycline and quality of life assessed. The protocol was registered at clinicaltrials.gov (NCT01380262).Results: Between July 2010 and December 2011 fourty two consecutive patients were enrolled to the study. Out of these 3 has discontinued the observation due to progression of disease before end of the observation period. There were 11 patients (week 2; 2W), 15 patients (4W), 20 patients (6W) and 22 patients (8W) with skin toxicity >= 2 grade. The most frequent toxicity >= grade 2 was acne-like rash. The grade 3 acne-like rash was observed in 0% (2W), 4.8% (4W), 10% (6W) and 10.2% (8W). The second most frequent toxicity was xerosis. No grade 4 toxicities were observed. Eight patients (19%) discontinued doxycycline (temporary or completely) due to adverse events.Conclusion: Oral doxycycline at the single dose of 100 mg daily during anti-EGRF treatment of CRC patients is safe and effective in prevention of skin rash and majority of other skin side effects, beside the xerosis. Introduction: Over 80% of colorectal cancer (CRC) patients treated with anti-EGFR antibodies (cetuximab or panitumumab) suffer from various types of skin toxicity – including acne-like rash, xerosis, paronychia or telangiectasia. The prospective clinical trial phase II (STEPP) proved that the primary prophylaxis with oral doxycycline (200 mg daily), topical steroids and sun blockers was efficacious. To further test the efficacy of systemic doxycycline we planned a single arm phase II prospective study of lower dose doxycycline (100 mg daily orally) in prevention of anti-EGFR skin toxicity in CRC patients. Methods: Eligibility included CRC qualified for treatment with panitumumab or cetuximab, WHO status of 0-2, age ≥18 years, lack of contraindications for using doxycycline and informed consent. The primary outcome was a number of patients with skin toxicity ≥ 2 grade during 8 weeks observation. The secondary outcome measures were: occurrence of skin toxicities by type, compliance to protocol, reason for discontinuing the anti-EGFRs and doxycycline and quality of life assessed. The protocol was registered at clinicaltrials.gov (NCT01380262). Results: Between July 2010 and December 2011 fourty two consecutive patients were enrolled to the study. Out of these 3 has discontinued the observation due to progression of disease before end of the observation period. There were 11 patients (week 2; 2W), 15 patients (4W), 20 patients (6W) and 22 patients (8W) with skin toxicity >= 2 grade. The most frequent toxicity >= grade 2 was acne-like rash. The grade 3 acne-like rash was observed in 0% (2W), 4.8% (4W), 10% (6W) and 10.2% (8W). The second most frequent toxicity was xerosis. No grade 4 toxicities were observed. Eight patients (19%) discontinued doxycycline (temporary or completely) due to adverse events. Conclusion: Oral doxycycline at the single dose of 100 mg daily during anti-EGRF treatment of CRC patients is safe and effective in prevention of skin rash and majority of other skin side effects, beside the xerosis.