vitamin-k-1 and Neoplasm-Metastasis

Acne-like skin reactions frequently occur in patients undergoing treatment with drugs inhibiting the epidermal growth factor receptor. Recently, the effects of vitamin K1 containing cream (Reconval K1) as prophylactic skin treatment in addition to doxycycline were explored in a double-blind randomized phase II trial (EVITA) in patients with metastatic colorectal cancer receiving cetuximab. EVITA demonstrated a trend towards less severe skin rash in Reconval K1-treated patients using the tripartite WoMo skin reaction grading score as a thorough tool for quantification of drug related skin reactions. This gender-specific analysis of the EVITA trial evaluated the application of the WoMo score for assessment of epidermal growth factor receptor (EGFR)-related skin toxicities according to treatment arm and gender. To show the robustness of results parametric and non-parametric statistical analyses were conducted. All three parts of the WoMo score independently demonstrated the superiority of the treatment arm (Reconval K1) regarding a significant reduction in acneiform skin reactions in women. Men did not benefit from Reconval K1 cream at any time point in none of the WoMo score analyses. The treatment effect in women was confirmed by the use of skin rash categories based on the final WoMo overall score and mixed effect longitudinal multiple linear regression analysis. The WoMo score represents a sensitive tool for studies exploiting treatments against EGFR mediated acne-like skin rash. Part C of the WoMo score seems to be sufficient for quantification of drug related skin toxicities in further studies. Standard WoMo skin reaction score values for future studies are provided.

Topics: Acneiform Eruptions; Adult; Aged; Aged, 80 and over; Cetuximab; Colorectal Neoplasms; Double-Blind Method; ErbB Receptors; Female; Humans; Male; Middle Aged; Neoplasm Metastasis; Protein Kinase Inhibitors; Sex Characteristics; Skin Cream; Treatment Outcome; Vitamin K 1

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

Topics: Bile; Bile Duct Neoplasms; Biliary Tract; Biliary Tract Diseases; Cholangiography; Cholelithiasis; Cholestasis; Contrast Media; Diagnosis, Differential; Female; Gallstones; Hemorrhage; Hepatitis; Humans; Liver Diseases; Male; Methods; Neoplasm Metastasis; Pancreatic Neoplasms; Peritonitis; Prothrombin Time; Vitamin K 1