Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0025202 (melanoma)
 69,561 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

16 patients with cutaneous or subcutaneous melanoma recurrence on an extremity were treated with regional perfusion with Melphalan. 18 perfusions were performed on 15 patients with stage II disease, that is with tumor growth restricted to an extremity including possible regional node metastases. All patients except two had new recurrences within the observation time. However, many of the patients had been treated surgically for recurrences once or several times previously. By comparing the length of the recurrence-free period following surgery alone with that following surgery plus perfusion in the same patients it was shown that perfusion treatment gave a significant extension of the recurrence-free time. Four perfusions were performed on patients in stage III, that is those with distant metastases. These perfusions gave a moderate or good temporary palliation as regards to tumor growths on the extremity. The traditional treatment for melanoma recurrences on an extremity has been surgical excision or less often amputation. An analysis of the literature shows that perfusion, usually combined with excision, seems to give definitely better results than surgical excision alone. There is evidence to suggest that perfusion treatment is even superior to amputation as regards survival; if so an immunological mechanism might be responsible for this effect.
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PMID:The effect of regional perfusion treatment on recurrent melanoma of the extremities. 85 20

Because of their initial appearance on extremities, malignant melanomas lend themselves to isolated chemotherapeutic perfusions. Perfusion is attractive because one can deliver effective cytotoxic drugs without systemic toxicity. We are reviewing 20 patients treated between 1960 and 1973 with isolated perfusion. Melphalan (L-phenylalanine mustard) was the drug of choice. Eleven of the 20 patients had previous surgical treatment. Three of the 11 patients are still alive from 27 to 72 months postperfusion. Eight died after an average survival time of 33 months. Of the seven patients who underwent perfusion as primary therapy, four patients are alive from 25 to 76 months postperfusion, and three died after an average survival time of 34 months. There is direct correlation between stages and levels of melanoma, and perfusion and prolonged survival time.
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PMID:Perfusion therapy for extremity melanoma. 94 57

Excision of the primary and isolation-perfusion with 1-phenylalanine mustard was the treatment in 199 patients with invasive Stage I melanoma of the extremities with the goal of improving regional disease control and long-term survival. The determinant survival in patients followed 5-15 years was 83%; Berkson-Gage survivals were 98% at 2 years, 88% at 5 years, and 84% at 10 years. The site of first recurrence was determined in all 49 (25%) patients who failed treatment: three (2%) developed local recurrence, six (3%) developed intransit recurrence, 24 (13%) developed positive regional lymph nodes, 15 (8%) developed systemic metastases, and one developed local recurrence plus positive regional nodes. Of these 49 patients failing treatment, 15 (31%) are currently surviving with no evidence of disease after retreatment of the recurrence. These data are compared to historical controls in the literature. It is concluded that regional control rates are improved by perfusion and that survival has probably been improved. In 14 patients treated by perfusion without local excision, regional control and survival was poor. Single drug (L-PAM) perfusion with the techniques employed is effective in controlling regional subclinical disease, but the primary should be widely excised.
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PMID:Survival and regional disease control after isolation-perfusion for invasive stage I melanoma of the extremities. 124 54

Carmethizole hydrochloride [1-methyl-2-methylthio-4,5-bis(hydroxymethyl)imidazole-4', 5'-bis(N-methylcarbamate)hydrochloride, NSC 602,668; hereafter called carmethizole] is a new antitumor drug that has shown relatively broad activity in initial evaluations against several murine tumors and human tumor xenografts in vivo. The present studies were designed to address questions about carmethizole's activity against established disease, its activity on different treatment schedules, and the extent of its cross-resistance with established drugs. Human MX-1 mammary carcinoma, human NCI-H82 small-cell lung carcinoma, and human LOX amelanotic melanoma xenografts in athymic mice were used to determine the drug's activity against established disease; the NCI-H82 lung-tumor xenograft in athymic mice was used to explore its schedule dependence; and a series of drug-resistant murine leukemias provided an in vivo cross-resistance profile. When injected i.p., carmethizole exhibited antitumor activity against advanced-stage s.c. MX-1 mammary, s.c. NCI-H82 lung, and i.p. LOX melanoma xenografts and was as effective against established disease (MX-1 and LOX) as it was against early-stage disease (no data are available for early-stage NCI-H82). The therapeutic effect of carmethizole was not route-dependent, as was evidenced by the similar delays observed in tumor growth following i.p. and i.v. administration. The use of a split-dose schedule on a single day instead of one bolus injection yielded an increase in the total dose delivered, resulting in an increased delay in tumor growth. Murine leukemias resistant to vincristine (VCR), amsacrine (AMSA), or methotrexate (MTX) were not cross-resistant to carmethizole. However, murine leukemias resistant to doxorubicin (ADR), melphalan (L-PAM), cisplatin (DDPt), 1-beta-D-ara-binofuranosylcytosine (ara-C), and 5-fluorouracil (5-FU) were cross-resistant to carmethizole, suggesting that patients who have previously been treated with any of these agents might be less likely to respond to carmethizole than those who have had no opportunity to develop resistance to any of these compounds. We anticipate that the information derived from these studies may be useful in the design of clinical trials of carmethizole and may stimulate additional basic research on the mechanism of action of this new agent.
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PMID:Antitumor activity and cross-resistance of carmethizole hydrochloride in preclinical models in mice. 132 3

To increase the therapeutic efficacy of recombinant tumor necrosis factor alpha (rTNF alpha) and reduce the systemic side effects, a protocol was designed using isolation perfusion of the limbs with hyperthermia for in transit metastases of melanoma. A triple combination of high dose rTNF alpha + recombinant interferon-gamma (rIFN-gamma) + melphalan was chosen because of a synergistic anti-tumor effect of rTNF alpha with rIFN-gamma and of rTNF alpha with alkylating agents reported in the literature. Twenty-nine patients of mean age 60 years (range 22-82 years) entered the study after informed consent and received a total of 31 isolation perfusions with the triple combination. There were 24 women and 5 men with multiple progressive in transit melanoma metastases of the lower limb (stage IIIa or IIIab). rTNF alpha at the unique dose of 4 mg was injected as a bolus in the arterial line, under mild hyperthermic conditions (40 to 40.5 degrees C) for 90 minutes. rIFN-gamma was given subcutaneously on days -2 and -1 and in the perfusate, with rTNF alpha, at the dose of 0.2 mg. Melphalan was administered in the perfusate at dose giving a concentration of 40 micrograms/ml. In all the 31 isolation perfusions performed in the triple combination protocol, in order to prevent a septic shock-like syndrome which had been encountered in 2 patients treated outside this protocol for sarcoma and carcinoma, the patients received dopamine continuous infusion at 3 micrograms/kg/min from the start of isolation perfusion and for 48 hours, and only showed mild hypotension and very transient chills and temperature.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:In transit metastases of malignant melanoma treated by high dose rTNF alpha in combination with interferon-gamma and melphalan in isolation perfusion. 156 4

Thermochemotherapy through regional CEC has been applied to malignant melanomas of the limbs for a long time as it was described by Creech and Krementz more than twenty years ago. Strangely enough, its application has remained confidential in France. In order to assess this method, we have been applying it to 128 consecutive patients from January 1, 1982 to January 1, 1990. After the exclusion of 9 patients (7 technical failures, 1 wrong diagnosis, 1 improper inclusion), the remaining series is of 119 patients for 125 infusions. The average distance in time is 3.4 years. The series includes 31 men and 88 women with an average age of 51.2 + 14.2 years (23-75) with malignant melanoma of the upper limb (25 cases) or lower limb (94 cases). The histological type of the tumor was nodular in 47 cases (39.5%), SSM in 40 cases (33.6%), acrolentiginous in 26 cases (22%) and undetermined in 6 cases (5%). All lesions were high-risk malignant melanomas for which Clark's index was higher than III and Breslow's index higher than 1.5 mm in 103 cases (16 cases in which Breslow's index ranged from 1 to 1.5 mm were included at the beginning of the series). Chemotherapy utilized Mephalan with a dose of 0.8 to 1.5 mg/kg of body weight, delivered through monomelic CEC and under hyperthermia at 41 degrees C during 45 to 50 minutes, via a cannulation of the axillary artery and vein in the upper limb and of the common femoral artery and vein in the lower limb.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Monomelic thermochemotherapy for malignant melanoma of the limbs. Results of a homogeneous series of 128 patients]. 212 80

The pharmacokinetics and systemic availability of melphalan after high-dose oral administration with and without 1,3-bis(2-Chloroethyl)-1-nitrosourea (BCNU) or etoposide were examined in three patients undergoing autologous bone marrow transplantation. Patient 1 (advanced melanoma) received melphalan at 80 mg/m2/day p.o. on days -6, -5, and -4, followed by BCNU at 300 mg/m2/day i.v. on days -3, -2, and -1 prior to bone marrow transplantation. Patient 2 (advanced colon carcinoma) received melphalan at 75 mg/m2/day p.o. on days -3, -2, and -1. Patient 3 (advanced refractory lymphoma) received etoposide at 800 mg/m2/day i.v. on days -7, -5, and -3, followed by melphalan at 157 mg/m2/day p.o. on days -2 and -1. Melphalan was administered as a bolus oral dose, using 2-mg tablets. Blood samples were collected at 0, 5, 10, 15, 30, and 45 min and 1, 2, 3, 4, 6, 8, 12, and 24 h after each dose of melphalan. Peak plasma melphalan concentrations in the three patients ranged from 0.354 (patient 2) to 1.768 micrograms/ml (patient 1). Plasma melphalan concentration X time products (C x Ts) showed extreme variability in one patient (patient 2), ranging from 0.76 to 4.48 micrograms.h/ml. To determine the relative systemic availability of orally administered melphalan, i.v. C X Ts proportional to the p.o. doses were extrapolated from previously reported i.v. bolus pharmacokinetic data. The p.o.:i.v. plasma C X T ratios for high-dose melphalan ranged between 0.09 (patient 3) and 0.58 (patient 2). Although these C X T data suggest a dose-response for orally administered melphalan, the systemic availability of these high p.o. melphalan doses was extremely variable, both within and between study patients. Thus, we cannot recommend the use of high-dose p.o. melphalan regimens in patients undergoing autologous bone marrow transplantation.
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PMID:Pharmacokinetics of very high-dose oral melphalan in cancer patients. 230 18

Two different techniques [reduction of a tetrazolium derivative (MTT) and 3HTdR uptake assays] were compared in order to evaluate the cytotoxic effects of different chemotherapeutic agents in vitro. The cytotoxicities of Melphalan, hexamethylmelamine and seven derivatives, and daunorubicin were measured on P388D1 mouse macrophage-like cell line, RC mouse renal carcinoma cell line, and B16 mouse melanoma cell lines. Growth inhibition was determined after one hour as well as after continuous (48 hours) exposure to drugs. The IC50 was calculated using an appropriate algorithm (FADHA) which allowed within and between run variabilities to be taken into account. Optimal conditions had to be elucidated for culture conditions before assay: number of cells/well and assay duration for each line. The MTT and 3HTdR uptake assays were found to be similar in terms of sensitivity and reproducibility, both for adherent and floating cell lines. However, the MTT assay has the advantages of low cost and time saving. It also avoids problems related to radioactivity manipulation and counting. Both techniques rank the same chemicals as active or inactive. The algorithm Fadha was found to be a very powerful mathematical tool for comparing the IC50 values obtained by both assays.
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PMID:Comparison of two cytotoxicity assays--tetrazolium derivative reduction (MTT) and tritiated thymidine uptake--on three malignant mouse cell lines using chemotherapeutic agents and investigational drugs. 233 20

Melphalan inhibits the incorporation of 3H-thymidine and 3H-uridine significantly more in phytohaemagglutinin (PHA)-stimulated human lymphocytes than in a human melanoma cell line (RPMI 8322). Melphalan - induced total DNA cross-linking was 1.7 times higher and DNA interstrand cross-linking was 1.8 times higher in the PHA-stimulated lymphocytes than in the melanoma cells. A higher level of DNA cross-linking was required in melanoma cells than in PHA-stimulated lymphocytes to obtain similar levels of inhibition of incorporation of 3H-thymidine and 3H-uridine. The outflow of cells from G1 to S phase was significantly more inhibited by melphalan in the lymphocytes than in the melanoma cells. Thus the melanoma cells can replicate and transcribe DNA in the presence of levels of DNA damage, which in PHA-stimulated lymphocytes strongly inhibit DNA and RNA synthesis.
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PMID:Melphalan-induced DNA cross-linking and inhibition of DNA and RNA synthesis in human melanoma and lymphoblast cells. 234 4

In order to assess the potential interest of replacing the murine cell lines by human cell lines for in vitro cytotoxic assays, the sensitivity and the selectivity of the murine B16 and the human HBL melanomas to five chemotherapeutic drugs were investigated in vitro. The cytotoxicities of Melphalan, Daunorubicin (DNR), Hexamethylmelamine (HMM), Hydroxymethylpentamethylmelamine (HMPMM), and Dihydroxymethyltetramethylmelamine (DHTMM), 2 HMM derivatives, were measured in the two cell lines using two different techniques: reduction of a tetrazolium derivative (MTT) and tritiated thymidine uptake into DNA. The cytotoxicity at inhibitory concentration 50 (IC50) was determined after one hour as well as after 2 days exposure of cell after one hour as well as after 2 days exposure of cells to each drug. The results indicate that the HBL human melanoma was generally more sensitive to Melphalan and DHTMM than the B16 murine melanoma cells as far as the IC50 was concerned. In contrast, no difference of sensitivity was found to DNR and DHTMM. HMM was found to be inactive in both cell lines. The analysis of variance on IC50 values showed that the sensitivity of murine and human melanoma cell lines to drugs was statistically different. Despite the identical selectivity of the two cell lines, two promising observations can be made as far as the comparison of the two cell lines is concerned: 1) the higher sensitivity of HBL human cell line to Melphalan in the in vitro assays and 2) the slightly lower sensitivity of HBL to DNR, a drug without clinical activity against human melanoma.
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PMID:Compared cytotoxicity effects of five anticancer drugs on human (HBL) and mouse (B16) melanoma cells in vitro. 236 92


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