Disease relevance of Phenylalanine mustard

• Treatment with the four-drug combination was associated with a significantly increased overall response rate (75 vs. 54 per cent) (P less than 0.05), more complete remissions (33 vs. 16 per cent) and longer median survival (29 vs. 17 months) (P less than 0.02) but more severe toxicity than occurred with melphalan [1].
• The remaining patients with localized ovarian cancer should receive adjuvant therapy, and with adjuvant melphalan or intraperitoneal 32P should have a five-year disease-free survival of about 80 percent [2].
• 1-Phenylalanine mustard (L-PAM) in the management of primary breast cancer. A report of early findings [3].
• Resolution of acquired factor X deficiency and amyloidosis with melphalan and prednisone therapy [4].
• The four-drug regimen is more effective than melphalan in the management of advanced ovarian adenocarcinoma [1].

Psychiatry related information on Phenylalanine mustard

• High-dose melphalan appears to be a valuable agent for conditioning therapy in AML [5].
• Two parameters, temperature and intracellular glutathione (GSH) content, were varied to investigate the role of cellular defense mechanisms in the dye-sensitized photoinactivation of normal murine granulocyte/macrophage progenitors (CFU-GM) and K562, L1210, and melphalan-resistant L1210/L-PAM1 leukemia cells [6].
• A randomized prospective therapy trial in patients with stage III optimal epithelial carcinoma of the ovary was accomplished by the Gynecologic Oncology Group. Therapy with melphalan or melphalan plus immuno-adjuvant, Corynebacterium parvum (C. parvum), was utilized as adjuvant treatment following surgical therapy [7].
• Patients with advanced MM received 100 mg/day oral thalidomide escalated weekly up to 600 mg/day (n=23; T group), alone or with 0.20 oral mg/kg/die melphalan administered monthly for four consecutive days (n=27; TM group) [8].

High impact information on Phenylalanine mustard

• Dose-dependent risks were observed after radiotherapy and treatment with melphalan and cyclophosphamide [9].
• In the first trial, 81 patients with well-differentiated or moderately well differentiated cancers confined to the ovaries (Stages Iai and Ibi) were assigned to receive either no chemotherapy or melphalan (0.2 mg per kilogram of body weight per day for five days, repeated every four to six weeks for up to 12 cycles) [2].
• Acquired factor X deficiency and amyloidosis treated with melphalan and prednisone [10].
• Advanced ovarian adenocarcinoma. A prospective clinical trial of melphalan (L-PAM) versus combination chemotherapy [1].
• Furthermore, cells transfected with bovine papilloma virus expression vectors containing DNA encoding human metallothionein-IIA were resistant to cis-diamminedichloroplatinum(II), melphalan, and chlorambucil but not to 5-fluorouracil or vincristine [11].

Chemical compound and disease context of Phenylalanine mustard

• Eighty patients with advanced ovarian adenocarcinoma were treated in a prospective, randomized trial comparing a four-drug combination--hexamethylmelamine, cyclophosphamide, methotrexate and 5-fluorouracil--with the oral alkylating agent, melphalan [1].
• Dose-response curves in AKR or CD2F1 mice were obtained for AKR leukemia, L1210 leukemia, and hematopoietic stem cells following in vivo administration of one of the following anticancer agents alone or in combination with amphotericin B (AmB): doxorubicin, lomustine, or melphalan [12].
• Cisplatin and melphalan given ip exert a synergistic therapeutic effect against ascitic P388 leukemia in mice and have different dose-limiting toxic effects as well as favorable pharmacokinetic characteristics in ip phase I studies [13].
• Cellular loss of nonprotein thiols by treatment with BSO correlated with enhanced L-PAM toxicity; however, a far greater effect was achieved when this enzymatic inhibitor was used in combination with a hypoxic cell sensitizer [14].
• The present study deals with the identification of effector-cytotoxic cells that may be developed as a result of chemotherapy-induced tumor regression and their possible potentiation by active, specific immunization with melphalan- and glutaraldehyde-treated MOPC-315 plasmacytoma cells [15].

Biological context of Phenylalanine mustard

• We investigated the role of DNA repair in melphalan resistance in epithelial tumor cell lines [16].
• However, 3 stably expressed marker chromosomes were induced after 12 months of L-PAM treatment of line B6SUtA cl 27 [17].
• Macrophage activation, as measured by direct cytotoxicity against MOPC-315 targets, was found to occur locally and early following the event of melphalan-induced tumor regression [15].
• A phase I/II study of granulocyte colony stimulating factor (G-CSF) was undertaken in patients with advanced malignancy receiving melphalan to determine the granulocyte response, side-effects, and pharmacokinetics [18].
• Dual targeting is involved; TNF-alpha and IFN-gamma induce apoptosis of angiogenic endothelium, while melphalan induces apoptosis of tumour cells [19].

Anatomical context of Phenylalanine mustard

• Conversely, homoleucine is twice as effective in reducing the toxicity of melphalan for L1210 cells as it is for bone marrow cells [20].
• Weekly, twice weekly, or daily (3 X 10(-6)M) L-PAM treatment of IL-3-dependent cell lines induced gradual L-PAM adaptation in the absence of a detectable change in the maximum binding capacity of 125I-labeled IL-3 [17].
• METHODS: Melphalan cytotoxicity was determined in 14 epithelial tumor cell lines by use of the sulforhodamine assay [16].
• When in vitro killing of MOPC-315 targets was tested with the use of peritoneal macrophages harvested shortly following cure of ascitic tumor by ip injected melphalan, the cytotoxic response was significantly enhanced [15].
• METHODS: 161 patients between 16 and 60 years of age with relapsed Hodgkin's disease were randomly assigned two cycles of Dexa-BEAM (dexamethasone and carmustine, etoposide, cytarabine, and melphalan) and either two further courses of Dexa-BEAM or high-dose BEAM and transplantation of haemopoietic stem cells [21].

Associations of Phenylalanine mustard with other chemical compounds

• When SR-4233 was administered just before single-dose treatment with CDDP, CPM, BCNU, or L-PAM, however, marked dose enhancement leading to increased cytotoxic effects on tumor cells and on bone marrow cells was observed [22].
• Radiopharmaceutical therapy of 5T33 murine myeloma by sequential treatment with samarium-153 ethylenediaminetetramethylene phosphonate, melphalan, and bone marrow transplantation [23].
• Cross-trial analysis suggests that M7 is comparable to melphalan and prednisone or melphalan, prednisone, and vincristine; that the efficacy of ABCM in the Vth trial and VIth MRC trials is comparable; and that ABCM gave better survival than intermittent melphalan regimens in the prognostic groups analysed [24].
• In the Vth MRC myelomatosis trial, the survival of 314 patients randomised to receive ABCM (adriamycin, BCNU, cyclophosphamide, and melphalan) as first-line treatment was significantly longer than that of 316 patients given intermittent melphalan (M7) (p = 0.0003) [24].
• Therapeutic recommendations include plateletpheresis for major thrombo-hemorrhagic phenomena, or megakaryocyte suppression with radioactive phosphorus, alkylating agents (such as melphalan), or hydroxyurea; minor symptoms may respond to platelet antiaggregating agents [25].

Gene context of Phenylalanine mustard

• However, activation of only Notch-1, but not Notch-2, resulted in protection of tumor cells from melphalan- and mitoxantrone-induced apoptosis [26].
• PURPOSE: Isolated limb perfusion (ILP) with tumor necrosis factor (TNF), interferon gamma, and melphalan (M) has been reported to result in high response rates for extremity melanoma and sarcoma [27].
• We also found that three other Flt1-expressing neuroblastoma cell lines show hypoxia-mediated drug resistance to etoposide, melphalan, doxorubicin, and cyclophosphamide [28].
• Role of multidrug resistance protein 1 (MRP1) and glutathione S-transferase A1-1 in alkylating agent resistance. Kinetics of glutathione conjugate formation and efflux govern differential cellular sensitivity to chlorambucil versus melphalan toxicity [29].
• Melphalan induced also severe hepatotoxicity in the isolated recirculating perfused mouse liver from wild-type mice but not from TNFR 1 or 2 knockout mice [30].

Analytical, diagnostic and therapeutic context of Phenylalanine mustard

• After a median follow-up of more than six years, there were no significant differences between the patients given no chemotherapy and those treated with melphalan with respect to either five-year disease-free survival (91 vs. 98 percent; P = 0.41) or overall survival (94 vs. 98 percent; P = 0.43) [2].
• In this trial (median follow-up, greater than 6 years) the outcomes for the two treatment groups were similar with respect to five-year disease-free survival (80 percent in both groups) and overall survival (81 percent with melphalan vs. 78 percent with 32P; P = 0.48) [2].
• Treatment failures occurred in 22 per cent of 108 patients receiving placebo and 9.7 per cent of 103 women given L-PAM (p = 0.01) [3].
• Prolonged 1-phenylalanine mustard (L-PAM) administration as an adjuvant to mastectomy in the management of patients with primary breast cancer and pathologically positive axillary nodes was evaluated by a prospective, randomized, clinical trial [3].
• Carcinoma of the breast. Occurence after treatment with melphalan for multiple myeloma [31].

References