To evaluate and confirm efficacy and safety of electrochemotherapy with bleomycin or cisplatin on cutaneous and subcutaneous tumour nodules of patients with malignant melanoma and other malignancies ...in a multicenter study.
This was a two year long prospective non-randomised study on 41 patients evaluable for response to treatment and 61 evaluable for toxicity. Four cancer centers enrolled patients with progressive cutaneous and subcutaneous metastases of any histologically proven cancer. The skin lesions were treated by electrochemotherapy, using application of electric pulses to the tumours for increased bleomycin or cisplatin delivery into tumour cells. The treatment was performed using intravenous or intratumoural drug injection, followed by application of electric pulses generated by a Cliniporator™ using plate or needle electrodes. Tumour response to electrochemotherapy as well as possible side-effects with respect to the treatment approach, tumour histology and location of the tumour nodules and electrode type were evaluated.
An objective response rate of 85% (73.7% complete response rate) was achieved on the electrochemotherapy treated tumour nodules, regardless of tumour histology, and drug used or route of its administration. At 150 days after the treatment (median follow up was 133 days and range 60–380 days) local tumour control rate for electrochemotherapy was 88% with bleomycin given intravenously, 73% with bleomycin given intratumourally and 75% with cisplatin given intratumourally, demonstrating that all three approaches were similarly effective in local tumour treatment. Furthermore, electrochemotherapy was equally effective regardless of the tumour type and size of the nodules treated. Side-effects of electrochemotherapy were minor and acceptable, as reported by the patients.
We demonstrated that electrochemotherapy is an easy, highly effective, safe and cost-effective approach for the treatment of cutaneous and subcutaneous tumour nodules of different malignancies. Electrochemotherapy can provide immediate clinical benefit in patients with advanced cutaneous and subcutaneous metastases.
Electrochemotherapy consists of chemotherapy followed by local application of electric pulses to the tumor to increase drug delivery into the cells. The aim of this Phase II clinical study was to ...evaluate the antitumor effectiveness of electrochemotherapy using intratumoral cisplatin administration on cutaneous tumor nodules in malignant melanoma patients. In 10 patients, 133 tumor nodules of different sizes were treated: (a) 82 tumor nodules were treated with electrochemotherapy; (b) 27 tumor nodules were treated with cisplatin; (c) 2 tumor nodules were treated with electric pulses; and (d) 22 tumor nodules were untreated. Four weeks after therapy, 78% objective responses were obtained in the electrochemotherapy group, and 38% objective responses were obtained in the cisplatin group. Exposure of tumor nodules to electric pulses without cisplatin treatment had no effect on tumor growth. Electrochemotherapy was well tolerated by all patients, and a good cosmetic effect was obtained, with only minimal scarring and a slight depigmentation of the skin. At 124 weeks of follow-up, a 77% control rate of the tumor nodules treated by electrochemotherapy was observed, compared to 19% for those that were treated with cisplatin only (P < 0.0001). Our results clearly demonstrate that electrochemotherapy with cisplatin is a highly effective approach for treatment of cutaneous malignant melanoma nodules. The advantages of this therapy include its simplicity, the short duration of treatment sessions, low cisplatin doses, and insignificant side effects, as well as the fact that it can be done on an outpatient basis.
The polymorphic CYP2D6 gene encoding debrisoquine hydroxylase has attracted much interest for its possible role in human pulmonary carcinogenesis. The purpose of this work was to determine the ...frequency of poor metabolizers (PM) and extensive metabolizers (EM) of debrisoquine in Slovene population of healthy individuals (n = 107), lung cancer patients (200) and melanoma patients (121). Polymorphism of CYP2D6 gene was studied by genotyping based on PCR analysis of the intron 3 exon 4 junction containing G to A mutation and one base pair deletion in exon 5, which are responsible for approximately 95% of poor metabolizer phenotype in Caucasians. In the healthy Slovene population 62.5% of individuals were identified as extensive metabolizers, 31% as extensive-heterozygous metabolizers and 6.5% as poor metabolizers of debrisoquine. The frequency of EM individuals was 70.5% in lung cancer patients and 64% in melanoma patients, the frequency of extensive-heterozygous subjects was 27% in lung cancer patients and 31% in melanoma patients. The frequency of PM individuals in the lung cancer patients was 2.5% and in melanoma patients 5%. The decrease in PM genotype in the group of Slovene lung cancer patients is similar to the decrease published for some other ethnic groups. Our results support the hypothesis that polymorphic CYP2D6 gene probably plays some, though not a prevalent role in chemical carcinogenesis. Poor metabolizer individuals appear to be less susceptible to lung cancer than EM individuals.
Background The aspartic proteinase cathepsin D is believed to be associated with proteolytic processes leading to the invasion and seeding of tumor cells. An association between cathepsin D tissue ...concentration and aggressiveness of tumors has been detected in different cancer types, as well as in metastatic melanoma.
Methods The concentration of cathepsin D was measured immunoradiometrically (ELSA‐CATH‐D kit, CIS Bio International) in the cytosols of 51 primary cutaneous melanomas (with Breslow index < 4 mm) to estimate the tissue concentrations of cathepsin D in early cutaneous melanoma.
Results A significantly elevated concentration of cathepsin D was measured in the tumor cytosols as compared to adjacent normal tissue (44.2 vs. 14.7 pmol/mg of total protein, P < 0.001).
Conclusions Our results indicate that cathepsin D is expressed at high levels by melanoma cells. The extremely high expression of cathepsin D in two of our patients, with later progression of the disease over a 42‐month follow‐up period, suggests a possible correlation between the cathepsin D tissue concentration and the prognosis of primary cutaneous malignant melanoma.
Anorectal malignant melanoma is a rare tumor and there is no consensus on whether aggressive or local management is more appropriate. Local sphincter-saving excision has been shown to have a higher ...recurrence rate than abdominoperineal resection, although there is no long-term survival difference between the two approaches. Therefore, new adjuvant treatment strategies to permit local sphincter-saving excisions are warranted. In our case, a large anorectal malignant melanoma was successfully treated preoperatively by electrochemotherapy with cisplatin that, by reducing the tumor size, enabled sphincter-saving local excision. Brachytherapy was postoperatively delivered to the excision site. Fourteen months after the beginning of treatment, the patient is without signs of local recurrence and is continent.
The optimal treatment of multiple cutaneous and subcutaneous metastases of melanoma still remains unresolved. There are many different possible treatment modalities. We present a case of melanoma on ...the calf in which multiple cutaneous and subcutaneous metastases were treated by electrochemotherapy with cisplatin. They completely responded for eight years. After eight years two nodules recurred and were treated by electrochemotherapy with cisplatin and again complete response was achieved. The case presents the advantages of electrochemotherapy of multiple cutaneous and subcutaneous metastases of melanoma, its relative simplicity, its minimal side effects and the possibility to treat recurrent disease as many times as needed, with long lasting complete responses.
Instructions for the use of bleomycin or cisplatin administered either systematically or locally and electric pulses delivered by the CliniporatorTM by means of invasive or non-invasive electrodes.
The optimal treatment of multiple cutaneous and subcutaneous metastases of melanoma still remains unresolved. There are many different possible treatment modalities. We present a case of melanoma on ...the calf in which multiple cutaneous and subcutaneous metastases were treated by electrochemotherapy with cisplatin. They completely responded for eight years. After eight years two new metastatic nodules occurred and were treated by electrochemotherapy with cisplatin and again complete response was achieved. The case presents the advantages of electrochemotherapy of multiple cutaneous and subcutaneous metastases of melanoma, its relative simplicity, its minimal side effects and the possibility to treat recurrent disease as many times as needed, with long lasting complete responses.
The skin acts as the first defence barrier against external environmental pollutants, including chemicals and UV radiation. Cytochrome P450 CYP1A1 and glutathione S-transferases (GSTs) found in ...melanocytes and skin basal layers were shown to participate both in the metabolism of xenobiotics and in detoxification of reactive oxygen species (ROS). In our study we analysed the distribution of single and combined CYP1A1, GSTM1, GSTT1 and GSTP1 genotypes contributing to inter-individual differences in metabolism of xenobiotics and ROS in 125 Slovenian healthy individuals and in 140 patients with sporadic malignant melanoma. Our results showed no statistically significant differences between melanoma patients and healthy controls in the frequency of polymorphic CYP1A1 and GST genotypes. The risk of developing melanoma was not significantly increased in individuals homo- or heterozygous for the CYP1A1*2A allele combined with GSTM1*0 genotype (OR: 1.86; 95% CI: 0.36-7.71), but increased slightly in carriers of CYP1A1*2A combined with both GSTM1*0 and GSTT1*0 genotypes (OR: 3.42; 95% CI: 0.36-29.6). Our results indicate that factors other than the polymorphic genes coding xenobiotic metabolising enzymes play a major role in protection against environmental carcinogenesis in human skin.
Purpose: To evaluate and confirm efficacy and safety of electrochemotherapy with bleomycin or cisplatin on cutaneous and subcutaneous tumour nodules of patients with malignant melanoma and other ...malignancies in a multicenter study. Patients and Methods: This was a two year long prospective non-randomized study on 41 patients evaluable for response to treatment and 61 evaluable for toxicity. Four cancer centers enrolled patients with progressive cutaneous and subcutaneous metastases of any histologically proven cancer. The skin lesions were treated by electrochemotherapy, using application of electric pulses to the tumours for increased bleomycin or cisplatin delivery into tumour cells. The treatment was performed using intravenous or intratumoural drug injection, followed by application of electric pulses generated by a Cliniporator using plate or needle electrodes. Tumour response to electrochemotherapy as well as possible side effects with respect to the treatment approach, tumour histology and location of the tumour nodules and electrode type were evaluated. Results: An objective response rate of 85% (73.7% complete response rate) was achieved on the electrochemotherapy treated tumour nodules, regardless of tumour histology, and drug used or route of its administration. At 150 days after the treatment (median follow up was 133 days and range 60-380 days) local tumour control rate for electrochemotherapy was 88% with bleomycin given intravenously, 73% with bleomycin given intratumourally and 75% with cisplatin given intratumourally, demonstrating that all three approaches were similarly effective in local tumour treatment. Furthermore, electrochemotherapy was equally effective regardless of the tumour type and size of the nodules treated. Side effects of electrochemotherapy were minor and acceptable, as reported by the patients. Conclusion: We demonstrated that electrochemotherapy is an easy, highly effective, safe and cost-effective approach for the treatment of cutaneous and subcutaneous tumour nodules of different malignancies. Electrochemotherapy can provide immediate clinical benefit in patients with advanced cutaneous and subcutaneous metastases.
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