Phytomenadione pre-treatment in EGFR inhibitor-induced folliculitis.

BACKGROUND: Targeted oncology therapy with inhibitors of epidermal growth factor receptor is associated with numerous cutaneous side effects. Acneiform eruptions are the most frequent skin toxicities reported. They may lead to impairment of patients' quality of life and sometimes may even become severe enough to necessitate the interruption or cessation of therapy. OBJECTIVE: To assess the possible effect of topical phytomenadione (vitamin K1 ) pre-treatment in diminishing the extent and severity of acne-like follicular rash associated with epidermal growth factor receptor inhibitor therapy. METHODS: A series of 20 patients with colorectal cancer or head and neck cancer were pre-treated with phytomenadione cream (0.05% in seven patients and 0.1% in 13 patients), starting morning before the first infusion of cetuximab or panitumumab, and followed up for the development of therapy-associated folliculitis. The cream was prepared from phytomenadione solution added to a hydrophilic cream base, oil in water, to obtain the concentration of 0.05% or 0.1%. RESULTS: Majority of patients (15 out of 20, 75%) pre-treated with phytomenadione cream experienced only mild, grade I acneiform eruptions. Five patients (25%) had grade II rash, which included two of seven patients pre-treated with 0.05% phytomenadione cream and three of 13 patients who used 0.1% phytomenadione cream. Topical phytomenadione cream was well tolerated and no abnormalities in blood coagulation were observed. CONCLUSIONS: Topical pre-treatment with phytomenadione cream might become useful in epidermal growth factor inhibitor-associated acneiform eruptions.

Cetuximab-induced cutaneous toxicity.

BACKGROUND: Epidermal growth factor receptor inhibitors are recently utilized by oncologists in advanced cases of certain malignancies. However, these agents are associated with numerous cutaneous adverse reactions. OBJECTIVE: To systematically review the cutaneous toxicity of cetuximab-treated patients. METHODS: An analysis of a series of 24 patients (20 men and 4 women) treated with cetuximab (12 patients with head and neck cancer and 12 patients with colorectal cancer) was performed with respect to relevant clinical characteristics. RESULTS: A total of 22 patients (91.7%) developed pustular or maculopapular follicular eruption, often referred to as acneiform rash. One patient (4.2%) developed paronychia in the course of cetuximab therapy. All patients with head and neck cancer had a combination treatment with radiotherapy and experienced radiation dermatitis accompanied by skin xerosis. Anaphylactic reaction was observed in three patients (12.5%). CONCLUSIONS: The most frequent cutaneous side effect reported in this series was acneiform eruption. The authors observed that all women with acneiform rash had only limited facial involvement, whereas all but one man experienced more widespread lesions of the face, the back and the chest. We found no association between the extent and severity of cutaneous eruptions (grade 1 vs. grade 2) and patients' response to therapy.

[Complications of radiotherapy--a medical problem?]. / Komplikace radioterapie--internistický problém?

The ever increasing number of solid tumours and revival of radiotherapy as the method of choice of locoregional treatment in particular in combination with surgery in curative treatment of not advanced diseases leads to the fact that the specialist in internal medicine is faced with early as well late postirradiation changes which may play a part in the differential diagnosis in internal medicine The radiation effects on the living organism can be divided into those conditioned by cellular losses (deterministic) and structural DNA changes in surviving cells (stochastic). Both types of changes must be taken into account in relation to the administered radiation dose, size and site of the irradiated volume, fractionation and time interval after radiation. Modern radiotherapy uses for axternal irradiation as well as for brachytherapy specialized equipment and facilities which make optimalization of treatment possible so that the defined clinical target volume is irradiated homogeneously by a defined dose with minimal damage of surrounding tissue. Contemporary oncological multimodal therapy is ever more successful, patients survive in a satisfactory clinical condition without signs of neoplastic disease for increasing periods of time. In the differential diagnosis in the subsequent development of every patient it is important to record in the case-history whether the patient was irradiated and when and it must be taken into consideration that late postirradiation changes are permanent and develop even several years after completed radiotherapy. In case of doubt, one way leading to a correct diagnosis (and thus also treatment) is consultation with the radiotherapist who treated the patient and who should follow him up permanently after completed treatment.

[Tamoxifen or tamoxifen in combination with chemotherapy in adjuvant therapy of breast carcinoma. Results of a multicenter randomized study]. / Tamoxifen nebo tamoxifen v kombinaci s chemoterapií v adjuvantní lécbe karcinomu prsu. Výsledky multicentrické randomizované studie.

UNLABELLED: Between April 1994 and May 1997 103 breast cancer patients (pts), pT1c-3a, pN0-1, M0, were randomised after surgery to adjuvant tamoxifen (20 mg per day) or to tamoxifen plus CMF (C 500 mg/m2, M 40 mg/m2 and F 600 mg/m2 on days 1st and 8th q 28 day) in 6 cycles. The median age (49-72 years, median 58), tumour size, number of involved lymphnodes (0-3), estrogens receptor status, grade (I-III) and type of operation were well balanced among the 50 pts on tamoxifen and the 53 pts on tamoxifen plus CMF pts, preferably postmenopausal. RESULTS: Grade of toxicity according to WHO criteria was not higher then two in both arms. Toxicity both haematological and non-haematological was higher in the group treated with chemotherapy (0 vs 32 resp. 20%) except weight gain (52% in both group). After median follow-up of 42 mos five recurrences in tamoxifen and seven in tamoxifen plus CMF pts were observed (p = NS). The projected 3-y DFS is 92% for tamoxifen and 88% for tamoxifen plus CMF (p = NS). The 3-y OS is 88% for tamoxifen and 80% for tamoxifen plus CMF pts (p = NS). CONCLUSIONS: Both regimens are equally effective with higher toxicity in the group with combined chemo- and hormonal therapy.

[Comparison of adjuvant chemotherapy in breast carcinoma with a combination of cyclophosphamide, methotrexate, 5-fluorouracil (CMF) and AC (doxorubicin, cyclophosphamide). Initial results of a national cooperative study]. / Srovnání adjuvantní chemoterapie karcinomu prsu kombinací cyklofosfamid, metotrexat, 5-fluorouracil (CMF) a AC (doxorubicin, cyklofosfamid). První výsledky národní kooperativní studie.

The aim of this multicentric, prospective randomized trial is to evaluate and to compare, effects and toxicities of two chemotherapeutic combinations (AC and CMF) in adjuvant treatment of breast cancer. Both combinations were given in equitoxic doses and number of cycles was only four. There are 106 women treated for breast cancer T1c-3a, N0-1, M0 in the study. After surgery the patients were randomized, 54 for AC combination and 52 for CMF. We evaluate toxicity of this treatment in all patients in the study. Hematological and nonhematological side effects were comparable in both groups except alopecia (in the group AC was 100%). The study is not finished yet. Preliminary analysis does not show any difference between these two groups.

[Morphologic basis of hemorrhage during hormonal therapy in the climacteric syndrome]. / Morfologický podklad krvácení pri hormonální terapii klimakterického syndromu.

In a group of 133 postmenopausal women in the course of nine years the relationship between two types of hormonal treatment and one of the side-effects--metrorrhagia--was investigated. This symptom was found in 37 patients. The authors followed two aims. To evaluate the relationship between treatment of the climacteric syndrome and the morphological state of the uterine mucosa and to assess the optimal therapeutic pattern under local conditions. The insignificant frequency of proliferating endometrial changes supports some data in the literature which draw attention also to other causes of haemorrhage. With regard to therapeutic regimes, the authors consider continual administration of conjugated oestrogens--0.625 mg and medroxyprogesterone acetate 5 mg per day as suitable. They emphasize the necessity to follow up the patients in a special clinic with the opportunity to make hormonal examinations and to ensure interdisciplinary collaboration.

Clinical experience with the testing of serum proteinase activity by cathepsin B-like sensitive amino acid derivatives of 7-amino-4-methylcoumarine.

The proteolytic activity of serum against two synthetic polypeptide substrates conjugated with 7-amino-4-methylcoumarine which are known to be highly specific substrates for lysosomal cathepsin B-like cysteine proteinase, was studied in normal individuals and in patients with breast and colorectal cancer. The results showed that both substrates are cleaved in different ways and their hydrolysis is very poorly sensitive to inhibitors of cysteine proteinases. On the other hand, cleavage is intensively inhibited by disodium-EDTA which is known as an activator of cysteine proteinases. This indicates that lysosomal conditions are quite different from serum which is an unstable mixture of various enzymes and their substrates. It was also demonstrated that hydrolysis of the tested substrates is not probably realized by cysteine proteinases but it can be performed by cooperation of other serum proteinases. Moreover, our results confirmed that serum activity of these enzymes can be significantly higher in patients with breast cancer, particularly with metastasis, than in healthy women. A slight insignificant increase was observed also in patients with colorectal cancer.