vitamin-k-1 and Exanthema

Acne-like skin rash is a frequently occurring adverse event associated with drugs against the epidermal growth factor receptor. This randomized vehicle-controlled study investigated the addition of vitamin K1 cream to doxycycline in patients with metastatic colorectal cancer treated with cetuximab.. Patients receiving first-line cetuximab + FOLFIRI were randomly assigned to prophylactic treatment with doxycylin and vitamin K1 cream or doxycycline and the vehicle. The primary end point of the study was the incidence of grade ≥ 2 skin rash (NCI CTCAE version 4.02) during 8 weeks of skin treatment. Secondary end points comprised skin rash according to a more thorough tripartite skin toxicity score (WoMo), quality of life, efficacy, and compliance. The study had 80% power to show a 20% reduction of the incidence of grade ≥ 2 skin rash.. A total of 126 patients were analyzed. The incidence of skin rash grade ≥ 2 was comparable between the arms. Likewise, no difference was seen in the WoMo score with respect to the percentage of skin affected. However, starting in week 5 and increasing over time patients treated with vitamin K1 cream had less severe rash and fewer fissures. Quality of life as well as efficacy and compliance with study medication and anticancer treatment was comparable in both arms.. The primary end point of decreasing grade ≥ 2 skin rash was not met. However, using vitamin K1 cream as part of prophylactic treatment decreased the severity of acne-like skin rash according to WoMo, an alternative and more thorough skin toxicity scoring tool.

Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Cetuximab; Colorectal Neoplasms; Double-Blind Method; Doxycycline; Exanthema; Female; Fluorouracil; Humans; Leucovorin; Male; Middle Aged; Neoplasm Metastasis; Patient Compliance; Pharmaceutical Vehicles; Quality of Life; Skin Cream; Vitamin K 1; Young Adult

Cetuximab-induced skin rash Gd3+ occurs in ≥16% patients (pts) (Heinemann et al., Lancet Oncol 15(10):1065-1075, 2014; Van Cutsem et al. J Clin Oncol 27(19):3117-25; 2009b). Survival, response, and toxicity parameters were re-evaluated under a pre-defined skin prophylaxis consistent of vitamin K1 ointment and oral doxycycline.. This is a national, multicenter, phase 4, first-line mCRC (K-RAS wt) trial. Pts received irinotecan 180 mg/m² (d1), FA 400 mg/m² (d1), 5-FU 400 mg/m² (d1), 5-FU 2400 mg/m² (d1-2), and cetuximab [400 mg/m² (d1), and then 250 mg/m² qw], prophylactic 0.1% vitamin K1 ointment qd, and oral doxycycline 100 mg bid.. 1-year PFS rate; secondary objectives: skin side-effects (grade, onset), objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS) time, and overall survival (OS) time and safety.. Twenty centers recruited 55 patients. Recruitment started Q1 2011 and ended Q3 2013 due to slow accrual. Characteristics were in line with CRYSTAL trial except for age and colonic location. 1-year PFS rate was 25.9%, mOS 21.8 months (m), and mPFS 8.5 m. ORR was 63.0%, DCR 77.8%. Rash Gd2+ occurred in 42.6% [median onset was 4.0 weeks (w)]; paronychia Gd2+ occurred in 22.2% (median onset 15.4w.); skin fissures Gd2+ occurred in 31.5% (median onset 19.9 weeks) 7% pts abandoned cetuximab treatment due to toxicity.. Our data reveal encouraging improvements in skin reactions and their time to occurrence due to a pre-defined skin care.

Topics: Adenocarcinoma; Administration, Cutaneous; Administration, Oral; Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Cetuximab; Chemoprevention; Colorectal Neoplasms; Doxycycline; Drug Eruptions; Exanthema; Female; Fluorouracil; Humans; Leucovorin; Male; Middle Aged; Neoadjuvant Therapy; Neoplasm Metastasis; Ointments; Skin Care; Treatment Outcome; Vitamin K 1

Cetuximab is an effective option for the treatment of metastatic colorectal cancer in the first and subsequent lines of treatment; among its side effects, acneiform skin rash is one of the major causes of treatment delay, reduction, or interruption, with a negative effect on quality of life. No effective strategy to prevent skin rash induced by epidermal growth factor receptor inhibitors is available; however, encouraging results have come from vitamin K1, phytomenadione, applied as a topical formulation. Available studies have been conducted in heterogeneous populations and are mainly focused on the use of vitamin K1-based cream for the treatment, rather than the prophylaxis, of acneiform rash.. Forty-one consecutive patients from a single center all affected by metastatic colorectal cancer and receiving cetuximab, alone or combined with chemotherapy, applied vitamin K1-based cream to prevent the occurrence of acneiform skin rash. The cream was applied twice a day on the face and trunk from the first day of administration of cetuximab.. The application of the cream was well tolerated. No grade 4 rash was reported. The proportion of grade 3 skin rash in the first 8 weeks of treatment in this population was 15%, at the lower limit of values reported in the literature, and the proportion of patients with grade 2 rash was reduced (22.5%).. This experience confirms available data in a homogeneous population, suggesting a possible benefit of topical vitamin K1 as prophylaxis for cetuximab-induced skin rash in patients with metastatic colorectal cancer.

Topics: Administration, Cutaneous; Aged; Antibodies, Monoclonal, Humanized; Antineoplastic Agents; Cetuximab; Colorectal Neoplasms; Exanthema; Female; Humans; Male; Neoplasm Metastasis; Pilot Projects; Skin Cream; Vitamin K 1

Skin toxicity in patients receiving novel therapeutic cancer agents has become a very important marker in determining drug activity, but it can also severely impact their quality of life. About half of the patients receiving this type of oncologic treatment will develop cutaneous reactions, that is why adequate understanding and management of these side effects is very important for drug adherence and patients' quality of life.. We conducted a prospective study of consecutive patients who received oncologic treatment in our institution and presented with dermatologic side effects. The severity of skin toxicity was assessed using the DLQI score and patients were prospectively followed to evaluate response to therapy. Univariate analysis of factors influencing the impact of skin toxicity on patient QOL was conducted.. 52 patients were enrolled in the study. Patients who developed grade 3 and 4 skin toxicity had a higher DLQI score, with a greater impact on quality of life, but with better clinical outcome at 3 months follow-up, based on RECIST. Patients with moderate or severe cutaneous AE were more likely to achieve complete or partial response to therapy than those with mild AE (16/33 vs. 3/19, p = 0.035). Interestingly, female patients had a significantly poorer quality of life than male patients as assessed by the DLQI score (7.28 ± 7 vs. 3.7 ± 3.6, p = 0.038).. Cutaneous side effects are often encountered in cancer patients and their severity can be a surrogate marker for a positive clinical tumor response to therapy.

Topics: Adrenal Cortex Hormones; Aged; Anti-Bacterial Agents; Antineoplastic Agents; Drug Eruptions; ErbB Receptors; Exanthema; Female; Humans; Male; Middle Aged; Neoplasms; Prospective Studies; Protein-Tyrosine Kinases; Quality of Life; Severity of Illness Index; TOR Serine-Threonine Kinases; Vitamin K 1; Vitamins

Topics: Cetuximab; Chin; Double-Blind Method; Exanthema; Humans; Vitamin K 1

Treatment with cetuximab is accompanied by the development of an acneiform follicular skin exanthema in more than 80 % of patients. Severe exanthema (grade III/IV) develops in about 9-19 % of patients with the necessity of cetuximab dose reduction or cessation.. The study presented was a retrospective analysis of 50 gastrointestinal cancer patients treated with cetuximab in combination with either FOLFIRI or FOLFOX. One cohort of 15 patients received an in-house reactive skin protocol upon development of an exanthema. A second cohort of 15 patients received a skin prophylaxis starting with the first dose of cetuximab before clinical signs of toxicity. A third historic group of 20 patients had received no skin prophylaxis or reactive treatment.. 19/20 patients of the historic group developed a skin exanthema. Grade III/IV exanthema was observed six times. Forty percent discontinued cetuximab therapy. The average time to exanthema onset was 14.7 days. Applying the reactive skin protocol after the first occurrence of an exanthema, the exanthema was downgraded as follows: No patients developed grade IV° exanthema, and two patients developed a grade II/III exanthema. In the majority of cases, the reactive skin protocol controlled the exanthema (grade 0-I°). No dose reductions in cetuximab were necessary. Applying the prophylactic skin protocol starting at the beginning of cetuximab application was not superior to the reactive skin protocol.. Cetuximab-induced skin exanthema can be coped with a reactive protocol equally effective as compared to a prophylactic skin treatment. A prospective study with higher patient numbers is planned.

Topics: Administration, Oral; Administration, Topical; Anti-Bacterial Agents; Antibiotic Prophylaxis; Antibodies, Monoclonal, Humanized; Antineoplastic Agents; Cetuximab; Detergents; Exanthema; Fluoroquinolones; Gastrointestinal Neoplasms; Humans; Metronidazole; Minocycline; Prednisolone; Quinolizines; Retrospective Studies; Treatment Outcome; Vitamin K 1

Topics: Adult; Exanthema; Female; Humans; Injections, Subcutaneous; Vitamin K 1