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Drug Design, Development and Therapy 2018Nitrogen mustard is a chemotherapeutic agent that has a well-documented safety and efficacy profile in the treatment of cutaneous T-cell lymphoma. Development of... (Review)
Review
Nitrogen mustard is a chemotherapeutic agent that has a well-documented safety and efficacy profile in the treatment of cutaneous T-cell lymphoma. Development of nitrogen mustard formulations and treatment regimens has been studied extensively over the last 40 years. In the last 5 years, a new gel formulation has been developed that is associated with a decrease in delayed hypersensitivity reactions. The authors in this review found that while the gel formulation may result in a decrease of allergic contact dermatitis, this advantage has been replaced by a higher number of irritant contact reactions and a decrease in complete response rate. The gel formulation has a complete response rate of 13.8%, which is a decrease in efficacy when compared to aqueous-based preparations of similar concentrations.
Topics: Administration, Cutaneous; Antineoplastic Agents, Alkylating; Drug Eruptions; Gels; Humans; Mechlorethamine; Mycosis Fungoides; Risk Factors; Skin Neoplasms; Treatment Outcome
PubMed: 29440874
DOI: 10.2147/DDDT.S137106 -
Dermatology Online Journal Feb 2001Cutaneous T-cell lymphomas are a heterogeneous group of cutaneous non-Hodgkin's lymphomas. In the United States, the incidence of these diseases is rising faster than... (Review)
Review
Cutaneous T-cell lymphomas are a heterogeneous group of cutaneous non-Hodgkin's lymphomas. In the United States, the incidence of these diseases is rising faster than any other cancer. Environmental triggers may be important in the evolution of malignancy. Current therapy is reviewed with emphasis on a new retinoid, Targretin.
Topics: Administration, Oral; Administration, Topical; Anticarcinogenic Agents; Apoptosis; Bexarotene; Biopsy; Carmustine; Disease Progression; Drug Eruptions; Humans; Hypertriglyceridemia; Lymphoma, T-Cell, Cutaneous; Mechlorethamine; Neoplasm Staging; PUVA Therapy; Prognosis; Retinoids; Sezary Syndrome; Tetrahydronaphthalenes; Vitamin D
PubMed: 11328624
DOI: No ID Found -
Acta Medica Portuguesa 1990After an historical review of the progressive improvement of Radiotherapy of Hodgkin's Disease, the authors present the actual management concepts with special reference... (Review)
Review
After an historical review of the progressive improvement of Radiotherapy of Hodgkin's Disease, the authors present the actual management concepts with special reference to prognostic factors. So, the actual strategy of Hodgkin's Disease aims above all not to lower the "cure" values lately reached but to reduce the iatrogenic pathology trying not to treat to much the good prognosis subgroups. These are susceptible of a less aggressive therapy by the knowledge of the relation cost/benefit of the intensive radiotherapy and the several multidrug regimens.
Topics: Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Combined Modality Therapy; Dacarbazine; Doxorubicin; Hodgkin Disease; Humans; Mechlorethamine; Prednisone; Procarbazine; Radiotherapy Dosage; Vinblastine; Vincristine
PubMed: 1692179
DOI: No ID Found -
Cutaneous and Ocular Toxicology Jun 2018Mass exposure to alkylating agents such as nitrogen mustard (NM), whether accidental or intentional as during warfare, are known to cause systemic toxicity and severe...
OBJECTIVE
Mass exposure to alkylating agents such as nitrogen mustard (NM), whether accidental or intentional as during warfare, are known to cause systemic toxicity and severe blistering from cutaneous exposure. Thus, establishing the timing and appropriate dose of any potential drug designed to reverse or impede these toxicities is critical for wound repair and survival. Our previous data demonstrates that a single intraperitoneal injection of low-dose 25-hydroxyvitamin D3 (25(OH)D) given as early as 1 h following NM exposure is sufficient to rescue mice from pancytopenia and death. However, the duration of time following exposure where intervention is still effective as a countermeasure is unknown. In this study, we sought to assess the maximal time permissible following NM exposure where 25(OH)D still affords protection against NM-induced cutaneous injury. Additionally, we determined if a higher dose of 25(OH)D would be more efficacious at time interval where low dose 25(OH)D is no longer effective.
METHODS
Low (5 ng) and high (50 ng) doses of 25(OH)D were administered intraperitoneally to mice following exposure to topical NM to assess wound resolution and survival. Mice were imaged and weighed daily to measure wound healing and to monitor systemic toxicity.
RESULTS
We demonstrated that 5 ng 25(OH)D administered as early as 1 h and as late as 24 h post-NM exposure is able to achieve 100% recovery in mice. In contrast, intervention at and beyond 48 h of NM exposure failed to achieve full recovery and resulted in ≥60% death between days 6 and 12, demonstrating the critical nature of timely intervention with 25(OH)D at each respective dose. In order to circumvent the observed failure at >48 h exposure, we provided two consecutive doses of 5 ng or 50 ng of 25(OH)D at 48 h and 72 h post-NM exposure. Repeat dosing with 25(OH)D at 48 h and beyond led to marked improvement of lesion size with 75% recovery from mortality.
CONCLUSIONS
The opportunity to use 25(OH)D as a medical countermeasure for NM-induced toxicity has a finite of window for intervention. However, modifications such as repeat dosing can be an effective strategy to extend the intervention potential of 25(OH)D.
Topics: Administration, Cutaneous; Animals; Calcifediol; Chemical Warfare Agents; Drug Administration Schedule; Female; Injections, Intraperitoneal; Mechlorethamine; Mice, Inbred C57BL; Wound Healing
PubMed: 28737434
DOI: 10.1080/15569527.2017.1355315 -
International Journal of Molecular... May 2021We developed two models of chemically induced chronic lung injury and pulmonary fibrosis in mice (intratracheally administered hydrochloric acid (HCl) and...
We developed two models of chemically induced chronic lung injury and pulmonary fibrosis in mice (intratracheally administered hydrochloric acid (HCl) and intratracheally administered nitrogen mustard (NM)) and investigated male-female differences. Female mice exhibited higher 30-day survival and less weight loss than male mice. Thirty days after the instillation of either HCl or NM, bronchoalveolar lavage fluid displayed a persistent, mild inflammatory response, but with higher white blood cell numbers and total protein content in males vs. females. Furthermore, females exhibited less collagen deposition, milder pulmonary fibrosis, and lower Ashcroft scores. After instillation of either HCl or NM, all animals displayed increased values of phosphorylated (activated) Heat Shock Protein 90, which plays a crucial role in the alveolar wound-healing processes; however, females presented lower activation of both transforming growth factor-β (TGF-β) signaling pathways: ERK and SMAD. We propose that female mice are protected from chronic complications of a single exposure to either HCl or NM through a lesser activation of TGF-β and downstream signaling. The understanding of the molecular mechanisms that confer a protective effect in females could help develop new, gender-specific therapeutics for IPF.
Topics: Animals; Collagen; Female; Gene Expression Regulation; HSP90 Heat-Shock Proteins; Humans; Hydrochloric Acid; Idiopathic Pulmonary Fibrosis; Lung; MAP Kinase Signaling System; Male; Mechlorethamine; Mice; Smad Proteins; Transforming Growth Factor beta
PubMed: 34072833
DOI: 10.3390/ijms22115909 -
Acta Dermato-venereologica Jun 2022Chlormethine is a bifunctional cytotoxic alkylating agent that binds to DNA, resulting in cell death (apoptosis). Chlormethine (also known as mechlorethamine) gel (CL...
Chlormethine is a bifunctional cytotoxic alkylating agent that binds to DNA, resulting in cell death (apoptosis). Chlormethine (also known as mechlorethamine) gel (CL gel) was approved in the European Union in 2017 and was first used in 2019. The aim of the study is to examine evidence regarding the efficacy and safety of chlormethine gel in everyday clinical experience from a cutaneous lymphoma centre. Twenty-three patients with stage IA-IIB mycosis fungoides received chlormethine gel between September 2020 and May 2021. All patients started by applying the gel daily and were monitored every month. At 1, 3, 6 and 9 months, 0%, 43.47%, 56.52% and 65.22% of patients, respectively, achieved an overall response. Five out of 23 patients (21.73%) achieved near complete response at a mean time of 6 months. Chlormethine gel was given as monotherapy in 12 patients (52.17%), and in addition to systemic treatments (methotrexate and peginterferon alpha-2a) in 11 patients (47.82%). Adverse events (AE) were recorded in 43.47% of patients, but only 3 discontinued treatment, due to dermatitis. Scale down of the treatment to application 3-times per week led to better patient compliance. This study shows that chlormethine gel is effective and safe in patients with mycosis fungoides with different types of skin lesions.
Topics: Antineoplastic Agents; Antineoplastic Agents, Alkylating; Humans; Mechlorethamine; Mycosis Fungoides; Skin Diseases; Skin Neoplasms
PubMed: 35199177
DOI: 10.2340/actadv.v102.1095 -
Anatomical Record (Hoboken, N.J. : 2007) Sep 2021Amino-Plex (SM1997) is a spray or liquid cosmeceutical that has been used for skin dryness, aging, or sun exposure. Its formulation includes electrolytes, trace...
Amino-Plex (SM1997) is a spray or liquid cosmeceutical that has been used for skin dryness, aging, or sun exposure. Its formulation includes electrolytes, trace minerals, amino acids, peptides, nucleosides and nucleotides, all substances that are <10 kDa. It is designed to increase oxygen levels in cells, improve glucose transport, stimulate ATP synthesis, and stimulate collagen formation, actions that can help facilitate repair of damaged cells. It also supports collagen synthesis and formation of healthy granulation tissue, accelerating reepithelization of damaged skin. Here, SM1997 has been tested as an agent to improve the healing of mustard injury to the cornea. The results indicate that SM1997 facilitates the retention of corneal epithelial attachment when applied to corneal organ cultures after nitrogen mustard exposure. In addition, it reduces the activation of enzymes that lead to epithelial-stromal separation, namely, ADAM17 and MMP-9. Therefore, SM1997 should be further investigated as a potential therapy sulfur mustard and nitrogen mustard exposure.
Topics: Collagen; Cornea; Epithelial Attachment; Mechlorethamine; Mustard Plant
PubMed: 33554453
DOI: 10.1002/ar.24597 -
Annals of Oncology : Official Journal... Jan 1991The availability of increasing numbers of active agents has led to the development of a succession of regimens for use as alternative and second-line therapy following... (Review)
Review
The availability of increasing numbers of active agents has led to the development of a succession of regimens for use as alternative and second-line therapy following relapse from or refractoriness to MOPP (mechlorethamine/vincristine/procarbazine/prednisone) or its variants. ABVD (doxorubicin/bleomycin/vinblastine/dacarbazine) has been the most widely used and has been considered non-cross-resistant. Other programs containing the nitrosourea lomustine have been used with results similar to those with ABVD. A relatively small fraction of relapsed patients remain failure free at 5 years (about 20% to 30%) despite a 30% to 60% second-line complete response (CR) rate. The few randomized trials (Cancer and Leukemia Group B [CALGB], European Organization for Research and Treatment of Cancer) evaluable to assess the efficacy of alternating MOPP/ABVD compared with MOPP alone have shown a small but significant advantage in freedom from progression and/or survival favoring the complex regimens over MOPP. The CALGB trial (8251) included a third arm of ABVD alone. The ABVD and MOPP/ABVD arms had a higher CR rate and superior failure-free survival (FFS) than did MOPP, but have thus far shown no difference between ABVD and alternating MOPP/ABVD, suggesting that full doses of a single regimen are equivalent to the more complex multidrug regimen. The next step in the CALGB program was to attempt to improve ABVD. The substitution of etoposide, an active single agent, for dacarbazine and bleomycin in ABVD resulted in a new regimen, EVA (etoposide/vinblastine/doxorubicin). This program has already demonstrated a 66% response rate in MOPP-resistant/relapsed patients (CALGB 8751).(ABSTRACT TRUNCATED AT 250 WORDS)
Topics: Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Bone Marrow Transplantation; Combined Modality Therapy; Dacarbazine; Doxorubicin; Hodgkin Disease; Humans; Mechlorethamine; Prednisone; Procarbazine; Prognosis; Remission Induction; Vinblastine; Vincristine
PubMed: 1710484
DOI: 10.1093/annonc/2.suppl_1.1 -
Clinical Lymphoma, Myeloma & Leukemia Feb 2021The pivotal 201 Study investigated chlormethine/mechlorethamine gel treatment for patients with early stage disease mycosis fungoides and demonstrated the treatment was...
Evaluating the Treatment Patterns of Chlormethine/Mechlorethamine Gel in Patients With Stage I-IIA Mycosis Fungoides: By-time Reanalysis of a Randomized Controlled Phase 2 Study.
BACKGROUND
The pivotal 201 Study investigated chlormethine/mechlorethamine gel treatment for patients with early stage disease mycosis fungoides and demonstrated the treatment was not inferior to chlormethine ointment. However, overall response rates do not provide information about response patterns. The study objective was to assess the value of by-time analysis of clinical response data in visualizing response over time.
METHODS
This post hoc analysis re-evaluated chlormethine efficacy using a by-time approach that investigated the trend to treatment response and permitted assessment of response, both monthly between 1 and 6 months, and once every 2 months between 7 and 12 months, over the course of 1 year. In addition, very good partial response was redefined as a ≥ 75% response.
RESULTS
By-time analyses of Composite Assessment of Index Lesion Severity (CAILS) and modified severity-weighted assessment tool (mSWAT) showed response rates at 1 month (respectively, 8.5% and 5.9%) that increased over time to peak at 10 months (78.9% and 54.4%). Early, intermittent, and late response patterns were observed. In total, 32.5% of patients experienced very good partial response over 2 consecutive visits, indicating that ∼ 33% of patients could expect to have very good to complete response within 1 year.
CONCLUSION
By-time analysis for clinical response provides complementary information to traditional overall response rate data regarding response peak time and changes over time.
Topics: Antineoplastic Agents, Alkylating; Clinical Trials, Phase II as Topic; Gels; Humans; Mechlorethamine; Mycosis Fungoides; Neoplasm Staging; Randomized Controlled Trials as Topic; Skin Neoplasms; Time Factors; Treatment Outcome
PubMed: 33358692
DOI: 10.1016/j.clml.2020.11.022 -
Toxicology and Applied Pharmacology Nov 2022Nitrogen mustard (NM) is a cytotoxic vesicant known to cause acute lung injury which progresses to fibrosis; this is associated with a sequential accumulation of pro-...
Nitrogen mustard (NM) is a cytotoxic vesicant known to cause acute lung injury which progresses to fibrosis; this is associated with a sequential accumulation of pro- and anti-inflammatory macrophages in the lung which have been implicated in NM toxicity. Farnesoid X receptor (FXR) is a nuclear receptor involved in regulating lipid homeostasis and inflammation. In these studies, we analyzed the role of FXR in inflammatory macrophage activation, lung injury and oxidative stress following NM exposure. Wild-type (WT) and FXR mice were treated intratracheally with PBS (control) or NM (0.08 mg/kg). Bronchoalveolar lavage fluid (BAL) and lung tissue were collected 3, 14 and 28 d later. NM caused progressive histopathologic alterations in the lung including inflammatory cell infiltration and alveolar wall thickening and increases in protein and cells in BAL; oxidative stress was also noted, as reflected by upregulation of heme oxygenase-1. These changes were more prominent in male FXR mice. Flow cytometric analysis revealed that loss of FXR resulted in increases in proinflammatory macrophages at 3 d post NM; this correlated with upregulation of COX-2 and ARL11, markers of macrophage activation. Markers of anti-inflammatory macrophage activation, CD163 and STAT6, were also upregulated after NM; this response was exacerbated in FXR mice at 14 d post-NM. These findings demonstrate that FXR plays a role in limiting macrophage inflammatory responses important in lung injury and oxidative stress. Maintaining or enhancing FXR function may represent a useful strategy in the development of countermeasures to treat mustard lung toxicity.
Topics: Acute Lung Injury; Animals; Cyclooxygenase 2; Heme Oxygenase-1; Irritants; Lipids; Lung; Macrophage Activation; Male; Mechlorethamine; Mice
PubMed: 35998709
DOI: 10.1016/j.taap.2022.116208