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.
