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Biomedical subjects

S Retsas

Publications and source records attributed to S Retsas.

At least 37 records · Page 2Linked to original sources
PubMed1996

Taxol and vinorelbine: a new active combination for disseminated malignant melanoma.

We evaluated the activity and toxicity of two sequences of taxol combined with vinorelbine in disseminated malignant melanoma, metastatic beyond regional lymph nodes. Fifteen previously untreated patients, nine males and six females (median age 56 years), were enlisted between May 1994 and February 1995. Eight patients received vinorelbine 30 mg/m2 (maximum dose 50 mg) first, follow 24 h later by taxol 120 mg/m2 (maximum dose 240 mg) infused over 3 h (the V/T sequence). Seven patients received the reverse (T/V) sequence. In 79 administered courses there were no anaphylactic episodes, the main toxicity being alopecia (WHO grade 3). Significant neutropenia, emesis or neuropathy was not observed in either schedule (WHO grades 0 or 1). Three major responses, all with the V/T sequences, were seen; one complete (CR) in nodal and cutaneous sites lasting 13 months and two partial (PR), omental, ascites in one and hepatic, splenic and nodal in the other, lasting 7 and 6 months, respectively. Clinically meaningful tumor regressions, not qualifying strictly for the criteria of major response, were observed in two additional patients in the T/V sequence. Taxol combined with vinorelbine is active against disseminated malignant melanoma. The importance of sequencing the two drugs remains to be determined with accrual of more patients into the study.

Adult↗
PubMed1996

The combination of paclitaxel with cisplatin exhibits antagonism in vitro against human melanoma.

The in vitro cytotoxicity of paclitaxel and cisplatin, alone and in combination, was evaluated against the established human melanoma cell line, G361, with either 1 or 24 h asynchronous paclitaxel exposure using the sulforhodamine B assay. As single agent, the mean cisplatin concentration which inhibited G361 cell growth by 50% (IC50) was 10,000 nM for 1 h exposure. IC50 values obtained with 1 and 24 h paclitaxel exposure were, respectively, 63 and 3.8 nM, concentrations clinically achievable. The combination of paclitaxel with cisplatin was found to be antagonistic by the classical isobologram method, independent of drug sequence and of paclitaxel exposure time. The antagonism was significantly more pronounced for the sequence of paclitaxel followed by cisplatin compared with the reverse sequence for both 1 and 24 h paclitaxel exposure time (p < 0.05). Future clinical protocols employing paclitaxel and cisplatin, both active single agents for the treatment of metastatic malignant melanoma, should take into consideration that the combination of the two drugs may result in significant antagonism, irrespective of drug sequence, if administered within a short interval of each other.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1994

Clinical and histologic involvement of regional lymph nodes in malignant melanoma. Adjuvant vindesine improves survival.

BACKGROUND: This report is a study of prognostic factors, including adjuvant chemotherapy, that influence survival of patients with malignant melanoma who have clinical and pathologic involvement of regional lymph nodes. METHODS: A total of 169 evaluable patients with malignant melanoma metastatic to regional lymph nodes were registered consecutively and prospectively between June 1977 and December 1986 in the computerized data base of the melanoma registry at Westminster Hospital. Eighty-seven of these patients received adjuvant chemotherapy with vindesine after resection of palpable metastatic lymph nodes, and 82 had no systemic treatment after surgery. All were followed up for at least 2 years (median, 8 years) after involvement of regional lymph nodes was noted or until death. Statistical analyses included simple life-table comparisons, unadjusted for covariates. In addition, Breslow's thickness, ulceration of the primary lesion, its anatomical location, number of regional lymph nodes histologically involved, dissection site, patient age and sex, and adjuvant vindesine therapy were included as covariates in Cox regression models. RESULTS: The disease-free interval (P = 0.0001), time to dissemination from lymph node metastases (P < 0.0001), survival time after lymph node dissection (P = 0.0227) and overall survival time after initial diagnosis of malignant melanoma (P = 0.0095, log-rank chi-square test) were superior for the 87 patients who received adjuvant chemotherapy with vindesine. Cox regression analysis confirmed adjuvant vindesine as a highly significant variable influencing all of these outcomes, including overall survival time after first diagnosis (P = 0.003). CONCLUSIONS: The apparent effect of adjuvant vindesine on overall survival in this study is large (hazard ratio, 0.52) and highly statistically significant. Adjuvant vindesine therapy merits consideration for malignant melanoma metastatic to regional lymph nodes. However, these results observed in concurrent, but nonrandomized, patients clearly require confirmation.

Adult↗
PubMed1994

Cutaneous melanoma-associated retinopathy.

PURPOSE: To define further the syndrome of cutaneous melanoma-associated retinopathy, of which only five affected patients have been reported previously. METHODS: Three men with melanoma-associated retinopathy were examined and studied electrophysiologically. Two were studied in detail psychophysically. RESULTS: Visual symptoms consisted of flickering black and white spots, shimmering patches of colors, and night blindness. The onset was acute and nonprogressive. Reduced amplitudes were observed in the flash electroretinographic b-wave and the pattern electroretinogram. Color vision, contrast sensitivity, and light- and dark-adapted perimetric sensitivities were abnormal. In one patient, the rate of dark adaptation was normal with elevated final cone and rod thresholds. CONCLUSIONS: Melanoma-associated retinopathy is a paraneoplastic syndrome distinct from cancer-associated retinopathy with a different visual prognosis. It may preferentially affect men.

Aged↗
PubMed1994

Activity of extracts of Kigelia pinnata against melanoma and renal carcinoma cell lines.

Serial dilutions of standardised water, ethanol, and dichloromethane extracts of the stembark and fruits of Kigelia pinnata were tested for their growth inhibitory effects against four melanoma cell lines and a renal cell carcinoma line (Caki-2) using two different (MTT and SRB) assays. Lapachol, a possible constituent of these extracts, together with known therapeutic antineoplastic agents, was also tested in the same way. The IC50 of each extract was measured after extracts were diluted to 100 micrograms/ml in 1% ethanol or water. Significant inhibitory activity was shown by the dichloromethane extract of the stembark and lapachol (continuous exposure). Moreover, activity was dose-dependent, the extract being less active after 1 h exposure. Chemosensitivity of the melanoma cell lines to the stembark was greater than that seen for the renal adenocarcinoma line. In marked contrast, sensitivity to lapachol was similar amongst the five cell lines. Lapachol was not detected in the stembark extract.

Antineoplastic Agents, Phytogenic↗
PubMed1992

Antiproliferative activity of vinorelbine (Navelbine) against six human melanoma cell lines.

We compared in vitro the cytotoxic activity of vinorelbine (VRB) (Navelbine, 5'-nor-anhydro-vinblastine) a novel Vinca alkaloid, with that of vinblastine (VBL) vincristine (VCR) and vindesine (VDS). Five continuous human melanoma cell lines (C32, G361, StMl11a, StMl12d and StMl14a) and a new line WHMel 1, were used in this study. In growth-inhibition assays, VDS and VRB exhibited comparable cytotoxicity against the C32 and G361 melanoma lines; the effect being dose- and time-dependent. VRB appeared less inhibitory compared to VDS in the lowest concentrations (0.1-1 nM). The same activity was observed with 0.1-1 microM. These drugs exhibited comparable growth inhibition at clinically achievable doses. The MTT assay was used to compare VBL, VCR, VDS, and VRB. Overall IC50 values (concentration required to reduce viability by 50%) ranged from 1 pM to 10 nM. The reduction in cell viability with VRB was similar to that observed with the reference drugs in four out of five lines tested by this method. However a trend was observed for IC50 values to be lower with VBL and VDS. In clonogenic assays (StMl11a, StMl12d and StMl14a lines, 1 h exposure) VRB and VDS produced the same reduction in survival. Survival curves were exponential followed by a terminal plateau. IC50 values ranged from 60 nM to 70 nM. Our results indicate that VRB has in vitro activity against six melanoma lines with differing phenotypic characteristics.

Antineoplastic Agents↗
PubMed1992

Metastasis to the penis from malignant melanoma: case report and review of the literature.

A case of metastatic malignant melanoma to the shaft of the penis is described and the literature reviewed to collate the incidence of primary sites which metastasize to the penis. Less than 260 cases of metastasis to the penis have been reported. Of these, 76% are from genitourinary primary sites and 17% are from gastrointestinal primary sites but only one case of metastatic melanoma to the penis has been previously reported. The described case presented with painful priapism while receiving combination chemotherapy for metastatic disease. A CT scan demonstrated a deposit in the left corpora cavernosa and needle aspiration cytology of a plaque attached to the shaft confirmed malignant melanoma cells. Palliation of the painful priapism was achieved by treatment with radiotherapy using large doses per fraction. Retrograde venous or lymphatic spread may have been the cause of a metastasis at this site. Prognosis is very poor.

Adult↗
PubMed1991

Alpha-interferons: impact on survival of patients with renal cell carcinoma.

We studied the effect of treatment on tumour response and survival of 76 evaluable patients with renal cell carcinoma, treated in this unit over a 12-year period. For the purpose of this study patients were classified into three groups according to the treatment they received: (a) 22-patients were evaluable for treatment with alpha-interferons; (b) 20 for treatment with immune modulation, other than interferon; (c) 34 patients received hormone treatment, chemotherapy or had no systemic treatment. Objective tumour regressions were observed only among patients who received interferon. No difference in overall survival from first diagnosis or from diagnosis of Stage IV disease could be demonstrated in these three groups. Alpha-Interferons are the first agents to induce clinically meaningful and reproducible regression of metastases in renal cell carcinoma. This treatment, however, has not been shown to have a major impact on survival.

Adult↗
PubMed1990

Lipophilicity of some substituted morpholine derivatives synthesized as potential antinociceptive agents.

Some substituted 2-alkoxy-morpholines have been synthesized as potential antinociceptive agents. These compounds share some structural characteristics of the piperidine analgesics. Their lipophilicity, expressed as log P (octanol-water) and as RM values (from reversed phase thin layer chromatography) was determined. Correlation of these two lipophilicity parameters indicated the classification of the tested compounds into two subgroups. Acute toxicity and, for some selected structures, analgesic activity are reported.

Analgesics↗
PubMed1990

Synthesis of 2-, 4- and 5-benzoylpyrrole-3-acetic acids and study of their in vitro effects on active oxygen species.

The isomeric benzoylpyrrole-3-acetic acids 2a-4a were synthesized on the basis of the known biological interest of analogous pyrrole-1- and pyrrole-2-acetic acids. The electrophilic benzoylation of ethyl pyrrole-2-acetate was found to give mixtures of the three substituted on the carbon atoms of the pyrrole ring isomers 2-4 in ratios which varied with the employed conditions. Experimental procedures were developed for the preferential formation of each one of the isomers in synthetically useful amounts. The involvement of the synthesized compounds in active oxygen intermediates was tested in vitro by examining their effect on lipid peroxidation using heat inactivated rat hepatic microsomes, and as hydroxyl radical scavengers, by determining the inhibition of formaldehyde production from the oxidation of DMSO. For comparison, some ESR spectra were recorded. It was found that 3 moderately inhibited lipid peroxidation, while all derivatives tested were potent hydroxyl radical scavengers. It is proposed that the reported compounds could find useful applications as protective agents against oxygen toxicity.

Acetates↗