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At least 19 recordsLinked to original sources
PubMed1975

Mechlorethamine desensitization in therapy for mycosis fungoides. Topical desensitization to mechlorethamine (nitrogen mustard) contact hypersensitivity.

Five patients with mycosis fungoides who had developed contact dermatitis to a nitrogen mustard, mechlorethamine hydrochloride, even in low concentrations (1 to 5 mg/100 ml), received daily total-body applications of extremely dilute solutions (0.01 to 0.1 mg/100 ml) of mechlorethamine. The concentrations of the drug were approximately doubled weekly if the patient could tolerate it, or they were raised more slowly if the patient could not. Attempts to desensitize one patient were discontinued since he was unable to tolerate a greater concentration than 1.0 mg/100 ml after trying for one year. Another patient was able to tolerate a concentration of 3 mg/100 ml after three months, at which time his skin had completely cleared and treatment was stopped. Three other patients were desensitized during a period of 8 to 13 months to the point of tolerating the full therapeutic concentration used in our clinic (20 mg/100 ml) without experiencing dermatitis or pruritus.

Administration, Topical↗
PubMed1985

PUVA therapy prevents sensitization to mechlorethamine in patients with psoriasis.

Two groups of 20 patients with psoriasis were treated with mechlorethamine applied topically (group A) or with PUVA combined with mechlorethamine (group B). In group B mechlorethamine was started after six PUVA treatments. Results showed a significant decrease of the incidence of contact dermatitis in group B (30%) compared with group A (75%). Allergic dermatitis, demonstrated by a positive patch test to mechlorethamine with an histology of eczema, was observed in 55% of patients in group A and 20% in group B. The incidence of irritant dermatitis was not significantly different in the two groups. Allergic dermatitis was observed later in group B: after an average of 32.2 applications of mechlorethamine compared with 25 applications in group A. Possible mechanisms responsible for these results are reduction of epidermal Langerhans cells by PUVA therapy and induction of antigen-specific suppressor T cells. Patients living far from a specialized centre might be treated initially with PUVA therapy then with mechlorethamine alone, at home. This schedule may reduce the incidence of contact dermatitis to mechlorethamine.

Adult↗
PubMedDate not supplied

Dominant lethal mutations induced in mouse spermatogonia by mechlorethamine, procarbazine and vincristine administered in 2-drug and 3-drug combinations.

Male mice were treated with mechlorethamine (2.0 mg/kg), procarbazine (100 mg/kg) and vincristine (0.67 mg/kg) alone, or in 2-drug and 3-drug combinations. 5 weeks later and continuing for 5-8 weeks, embryos fertilized by spermatozoa that were derived from drug-treated spermatogonia were evaluated for drug-induced dominant lethal mutations. Significant mutagenesis was detected for mechlorethamine alone, for 2-drug combinations including mechlorethamine and for 3-drug combinations. Combinations where mechlorethamine was given first were mutagenic whereas combinations where mechlorethamine was not given first were not. Some combinations were more cytotoxic to the germinal epithelium than others. The data suggest that mutagenesis by this combination of drugs which is used extensively in treating Hodgkin's disease is due primarily to the mechlorethamine and that the frequency of mutation-induction may be a function of the order of administration.

Animals↗
PubMed1977

Failure to induce tolerance to mechlorethamine hydrochloride.

In view of the contradictory results reported in the literature regarding induction of specific immunologic tolerance to mechlorethamine hydrochloride (HN2), the problem was reinvestigated using a "tolerogenic" schedule that had been reported to be effective. Mechlorethamine hydrochloride, 200 microgram, intravenously, was given weekly for five weeks before beginning topical therapy with it. In the test group, five of 13 patients (11 with mycosis fungoides and two with psoriasis) became contact sensitized to mechlorethamine. In another patient, what was probably a contact urticarial reaction developed. In the control group, five of 13 patients (12 with mycosis fungoides, one with parapsoriasis) became contact sensitized to mechlorethamine. Thus, 38% of the patients in both groups became contact sensitized to mechlorethamine. It is concluded that this tolerogenic schedule, just as others previously tried, was not effective in inducing specific tolerance to mechlorethamine.

Dermatitis, Contact↗
PubMed1977

The treatment of mycosis fungoides: adjuvant topical mechlorethamine after electron beam therapy.

The feasibility of employing adjuvant topical mechlorethamine after electron beam therapy in the treatment of patients with mycosis fungoides is demonstrated. Patients treated with a planned adjuvant topical mechlorethamine schedule had a median disease-free interval of 25 months compared to 17 months for the group treated with electron beam therapy alone. Projected relapse-free survivals are slightly better in the adjuvant group--37% versus 29%. Patients receiving adjuvant topical mechlorethamine after the electron beam were observed to have a low incidence of contact allergy to the medication. The topical medication can be continued if a contact allergy develops by using a planned desensitization program. We currently treat all mycosis fungoides patients with electron beam therapy, randomizing half to receive adjuvant topical mechlorethamine.

Administration, Topical↗
PubMed1986

Reversible mechlorethamine-associated hearing loss in a patient with Hodgkin's disease.

Mechlorethamine, when administered in massive doses (0.6-1.5 mg/kg) to cancer patients in several early studies, caused severe irreversible hearing loss. There have been no reports of ototoxicity with doses of 0.4 mg/kg or less. The authors describe a 36-year-old man who developed profound sensorineural hearing loss during his first cycle of MOPP chemotherapy for Hodgkin's disease. Cyclophosphamide was substituted for mechlorethamine in subsequent cycles and his hearing deficit resolved. This is the first reported case of reversible ototoxicity associated with currently recommended doses of mechlorethamine.

Adult↗
PubMed1976

Distinctive effects of mechlorethamine (NSC-762), cyclophosphamide (NSC-26271), and BCNU (NSC-409962) on transcription in Ehrlich cells.

Comparisons have been made between mechlorethamine, cyclophosphamide (CP), and BCNU as to the effects of chemotherapeutic drug levels on the transcription of RNA in vivo in Ehrlich cells. Mechlorethamine causes a dose-dependent depression in the synthesis of large Hn RNA transcripts in the nucleus and in the amount of large polysomal mRNA in the cytoplasm without apparent disturbance of polyadenylation and transport. Because of compensating increases in smaller Hn RNA and mRNA chains there is no inhibition of total RNA synthesis. CP seems to accelerate total Hn RNA and mRNA formation but inhibits polyadenylation. CP also produces an excess of short chains with only a minor depression of the synthesis of longer transcripts and messages. BCNU inhibits both RNA synthesis and polyadenylation but without disturbance of the size distribution of the polynucleotide chains. The results with mechlorethamine, in particular, are not easily explained on the basis of premature chain termination at the sites of DNA alkylation.

Adenosine Triphosphate↗
PubMed1986

Proton magnetic resonance (PMR) spectroscopic determination of mechlorethamine hydrochloride for injection in commercial unit doses.

A simple PMR spectroscopic method was developed for the quantitative determination of mechlorethamine hydrochloride for injection in commercial unit doses. Deuterium oxide was used as the PMR solvent and tert-butyl alcohol served as the internal standard. The mean +/- SD% recovery value of mechlorethamine hydrochloride from synthetic formulations was 99.5 +/- 0.83, with a coefficient of variation of 0.83%. The mean content of mechlorethamine hydrochloride in a group of ten commercial unit doses was 99.3% by the PMR method and 99.4% by the titrimetric method of U. S. P. XX.

Chemical Phenomena↗
PubMed1976

Intravenous desensitization to mechlorethamine in patients with psoriasis.

Eight patients with psoriasis who had developed contact allergy to mechlorethamine hydrochloride (nitrogen mustard) were subjected to a regimen of intravenous infusion of small amounts of the drug in an attempt to produce desensitization. Although three of eight developed negative patch tests and were presumed to be desensitized, only one patient was able to use the drug therapeutically, and then only for a period of eight months, after which allergy recurred. The other two patients whose allergic contact dermatitis was abolished by the infusions were unable to use mechlorethamine therapeutically because of pruritus. Seven patients experienced some adverse reaction to the infusion. Intravenous desensitization of psoriatic patients who are allergic to mechlorethamine was not successful enough as a useful clinical procedure to allow them to once again use the drug therapeutically.

Administration, Topical↗
PubMed1977

Topical mechlorethamine. Cutaneous changes in patients with mycosis fungoides after its administration.

Six patients with mycosis fungoides were treated with topical mechlorethamine hydrochloride for periods of two to four years. Clinical and histological studies for radiomimetic and radiodermatitis-like effects failed to demonstrate any abnormalities. The only observed changes were generalized hyperpigmentation of the skin and melanin-containing melanophages in the papillary dermis. We consider that the long-term use of topical mechlorethamine may be a safe form of therapy, but that a continuous indefinite follow-up of patients on this medication should be mandatory.

Administration, Topical↗
PubMed1988

Efficacy of sodium thiosulfate as a local antidote to mechlorethamine skin toxicity in the mouse.

The highly vesicant nature of the alkylating anticancer agent mechlorethamine (HN2, or nitrogen mustard) requires careful i.v. technique during its administration. Skin toxicity due to HN2 extravasation is severe and typically prolonged over several months. Mouse skin toxicity studies were carried out to find a local antidote to decrease the severity of tissue damage by this agent. Intradermal (i.d.) HN2 (0.005-0.5 mg) caused dose-dependent skin ulcers in the mouse. Isotonic sodium thiosulfate Na2S2O3 (0.167 M) or hypertonic (0.34 M) Na2S2O3 (0.05 ml) given immediately after HN2 significantly reduced the mean HN2 ulceration area and the total time of ulceration. Ineffective local HN2 antidotes included hyaluronidase, hydrocortisone, and sodium chloride, all given i.d. Topical applications of DMSO, cold, and heat were also ineffective. Sodium thiosulfate is believed to chemically neutralize reactive mechlorethamine-alkylating species and thus decrease skin toxicity. Thiosulfate dosing studies showed that a molar excess of at least 200:1 (Na2S2O3:HN2) was required for significant antidotal activity. If thiosulfate treatment was delayed 4-24 h after HN2, no antidotal effects were obtained. We conclude that sodium thiosulfate can decrease the severity of local tissue damage caused by HN2. It should be considered the antidote of choice in the setting of clinical HN2 extravasations.

Animals↗
PubMed1991

Topical mechlorethamine in the treatment of mycosis fungoides. Uniformity of application and potential for environmental contamination.

Topical mechlorethamine hydrochloride is commonly used in the treatment of mycosis fungoides and has been formulated in both aqueous and ointment vehicles. Two concerns regarding the topical application of mechlorethamine hydrochloride relate to the adequacy of skin coverage that can be attained by the patient and the extent to which others in the patient's household might be exposed to the drug. In this study six patients applied either aqueous or ointment vehicles containing a fluorescent dye. Subsequent examination of the skin under a Wood's lamp revealed a significant percentage of body surface area to be missed during application; several areas were noted to be missed most commonly. These observations have led to specific alterations in instructions given to patients regarding drug application. Examination of the surrounding environment showed minimal evidence of contamination.

Administration, Cutaneous↗
PubMed1986

Ultrastructural observation of Charcot-Leyden crystals in mechlorethamine-treated cutaneous lesions of histiocytosis X.

We were recently able to observe, by electron microscopy, Charcot-Leyden crystals in the cutaneous lesions of histiocytosis X (Letterer-Siwe disease) that had been treated by local applications of mechlorethamine. The occurrence of Charcot-Leyden crystals in skin lesions is infrequent; so far, these structures have been observed only in cases of facial (Lever's) eosinophilic granuloma and in incontinentia pigmenti. Although Charcot-Leyden crystals can at times be formed spontaneously in tissue lesions, the possibility that their formation was favored by the local action of mechlorethamine is considered.

Crystallization↗
PubMed1990

NMR studies of the conjugation of mechlorethamine with glutathione.

Many cancer cells are resistant to chemotherapeutic treatment with mechlorethamine and other alkylating agents. These drug-resistant cells often show an increase in the intracellular concentration of glutathione and an increase in the activity of glutathione-S-transferase when compared to the sensitive cells. Both of these components are thought to be involved with inactivation of the drug either through conjugation with glutathione or by hydrolysis. NMR spectroscopy was used to monitor the nonenzymatic conjugation of mechlorethamine with glutathione. Several intermediates along the pathway to the doubly glutathione substituted mustard, including both mustard-aziridinium adducts, can be observed. The assignment of the 1H NMR spectrum of these adducts are presented. At 30 degrees C, pH 7.0, no hydrolyzed mustard was detectable. With the use of 13C-labeled mustard, the conjugation reaction can be shown to proceed through an aziridinium intermediate rather than by direct nucleophilic substitution.

Glutathione↗
PubMed1986

Regional isolated limb perfusion of melanoma intransit metastases using mechlorethamine (nitrogen mustard).

Forty-two patients with intransit metastases of melanoma in a limb were treated by isolated regional perfusion chemotherapy using mechlorethamine (nitrogen mustard). Group 1 (n = 12) underwent treatment at low dose, less than 0.35 mg/kg, or low temperature, less than 38 degrees C. Group 2 (n = 30) received higher doses, 0.35 to 0.6 mg/kg, plus heat at 38 degrees C to 41 degrees C. No patient had evidence of disease outside the limb at the time of perfusion. The median follow-up time was 48 months (range, 1 to 9 years). Of the 42 patients, 29 had measurable lesions that responded as follows: group 1, complete response (CR) in two of ten and partial response (PR) in none; group 2, CR in six of 19 and PR in six of 19. The combined CR and PR rate of 12 of 19 in group 2 was significantly higher than that of group 1 (P less than .05). CR lasted only 2 months in the two patients of group 1, but persisted in the six patients of Group 2, four of whom are still alive free of disease at 16, 21, 33, and 40 months. Relapse-free control of disease in the limb was achieved in 36% of the patients in group 2 at 24 months, compared with 0% in group 1 (P less than .05). An overall survival of 74% at 48 months was observed in group 2, significantly higher than that of 64% for group 1 (P less than .05). The status of the regional lymph nodes (RLN) and the number of metastases did not affect tumor response. However, 77% of RLN-negative patients survived 48 months, in contrast to only 38% of RLN-positive patients (P less than .05). One patient died postoperatively of myocardial infarction. No serious systemic toxicity developed. Two patients who underwent repeat salvage perfusions developed a reversible peripheral neuropathy in the limb. Limb function was good after treatment, and dramatically improved in patients who had advanced satellitosis that responded to treatment. These results suggest that heated limb perfusion using mechlorethamine at an adequate dose can offer long-term control of intransit metastases in approximately one third of these patients, with preservation of good limb function and possible prolongation of survival.

Adult↗
PubMedDate not supplied

Stimulatory effect of low doses of mechlorethamine on humoral response of ovalbumin-immunized rabbits--comparison with levamisole.

The effect of low doses of mechlorethamine (1-10 micrograms/kg) and levamisole (2.5 mg/kg) on humoral response of rabbits immunized twice with ovalbumin (0.1 mg/kg) was compared. It was shown that mechlorethamine given in a dose of 5 or 10 micrograms/kg potentiates the increase in the level of serum anti-ovalbumin hemagglutinins; this increase is induced both after the first and the second (after 14 days) antigen administration. Levamisole acted similarly but with much lower efficiency.

Animals↗
PubMed1975

Mechlorethamine in psoriasis. Further attempts to induce immunological tolerance.

Further attempts to induce immunological tolerance in 29 psoriatic patients treated topically with mechlorethamine hydrochloride have not been successful using the intravenous route. The rate of sensitization achieved (65%) is not substantially different from the rate for those patients who had no attempt to induce tolerance (55.5%).

Adult↗
PubMed1990

Treatment of lower torso stages I and II Hodgkin's disease with radiation with or without adjuvant mechlorethamine, vincristine, procarbazine, and prednisone.

From 1956 to 1987, 60 patients with either lymphangiogram-staged or laparotomy-staged I-II lower torso presentations of Hodgkin's disease were treated with radiation with or without Mustargen (mechlorethamine), vincristine, procarbazine, and prednisone (MOPP). In 22 with inguinal/femoral or pelvic disease and 24 with abdominal disease, treatment consisted of radiation only. Fourteen other patients with abdominal disease received MOPP chemotherapy before radiotherapy. In 11, the chemotherapy was limited to two cycles. At 10 years, the determinate survival and freedom from progression rates for all patients were 82% and 72%, respectively. For patients with inguinal/femoral or pelvic disease who were treated with radiation only, the corresponding rates were 90% and 86%. For patients with abdominal disease who received radiation only, the determinate survival and the freedom from progression rates were only 66% and 50%, respectively. However, corresponding results for 14 patients with abdominal disease who were treated with MOPP and radiation were 100% and 92% (P = 0.033 and P = 0.009, respectively.

Abdominal Neoplasms↗