Search results for "Nitrogen mustard"

Combined Carboplatin plus Ifosfamide and Cisplatin in Patients with Advanced Ovarian Carcinoma. A Phase I–II Study

1998

Abstract Because of the relative lack of overlapping toxicity, carboplatin (PPL) and cisplatin (CDDP) can be easily combined for treatment of ovarian cancer to increase total platinum dose intensity. Ifosfamide (IFO), one of the most effective single agents in ovarian cancer, has a low hematological toxicity when administered in continuous infusion. From January 1991 to December 1993, 34 patients with advanced ovarian cancer, previously untreated with chemo- or radiotherapy, were enrolled in a phase I–II study with the aim of determining the maximum tolerated dose (MTD) of CDDP (on day 8 of a 28-day cycle) in combination with PPL (300 mg/m 2 on day 1) and IFO (4,000 mg/m 2 /24 h by continuo…

The addition of interleukin-2 to cyclophosphamide therapy can facilitate tumor growth of B16 melanoma.

1995

The role of interleukin-2 (IL-2) on tumor growth of B16F10 melanoma cells was assessed in two sets of mice with different immune status: normal (immunocompetent) mice and immunodeficient mice. The two sets of animals were treated with cyclophosphamide (CY) or IL-2 alone or with a combined therapy of CY+IL-2. On days 6 and 10 after tumor cell injection, we evaluated the incidence of hepatic B16 melanoma metastases and the percentage of hepatic volume occupied by metastatic tissue. We observed that the CY alone (300 mg/kg, days 3 and 8 post-tumoral inoculation) significantly reduced tumor growth in all treated mice; however, CY proved more effective in normal recipients than in immunodeficien…

Safety and efficacy of Temsirolimus in combination with Bendamustine and Rituximab in relapsed mantle cell and follicular lymphoma

2015

In this phase I/II study, we explored the combination of Temsirolimus with Bendamustine and Rituximab (BeRT) in patients with r/r follicular lymphoma (FL) or mantle cell lymphoma (MCL). Patients with 1-3 prior therapies received Bendamustine (90 mg/m(2), day 1+2) and Rituximab (375 mg/m(2), day 1) with Temsirolimus in doses from 25 to 75 mg added on day 1, 8, 15 of a 28-day cycle. Fifteen (11 MCL, 4 FL) patients were included in the phase I. Median age was 73 years and median pretreatment number was 2. No formal dose-limiting toxicity was observed. Dominant non-hematological side effects were fatigue in 11 (73%), nausea in 9 (60%), mucositis in 7 (47%) and vomiting in 6 patients (40%). Coug…

Synthesis and analysis of activity of a potential anti-melanoma prodrug with a hydrazine linker

2013

A potential anti-melanoma prodrug containing a phenolic activator, a hydrazine linker, and a nitrogen mustard effector - (N-{4-[bis-(2-chloroethyl)amino]benzoyl}-N'-(4-hydroxybenzyl)hydrazine) has been synthesized in seven steps. Spectrophotometric measurements of its oxidation by tyrosinase showed a rapid increase of absorbance at 337 nm. HPLC analysis demonstrated that two major products were formed. However, during the reaction one of the products was converted into the other. The stable product with a maximum of absorption at 337 nm was isolated and identified as 5,6-dihydroxy-1H-indazol-1-yl 4-[bis-(2-chloroethyl)amino]benzoate. It was formed by a cyclization of the enzymatically gener…

Pyrrolo[2,1-d][1,2,3,5]tetrazine-4(3H)-ones, a new class of azolotetrazines with potent antitumor activity.

2003

Pyrrolo[2,1-d][1,2,3,5]tetrazinones 10a-o, compounds that hold the deaza skeleton of the antitumor drug temozolomide, were prepared by reaction of 2-diazopyrroles 9 and isocyanates. Such a synthetic route represents, among those leading to azolotetrazinones reported so far, the only possible one since attempts to cyclize to the title ring system 2-amino-1-carbamoylpyrroles 11 or the mono substituted 2-triazenopyrrole 12 failed. Compounds 10 were screened at the National Cancer Institute (NCI) for their activity against a panel of about 60 human tumor cell lines. Most of them possess remarkable antineoplastic activity having GI(50) values in the low micromolar or sub-micromolar range and rea…

Antiblastic Drug Combinations with Ifosfamide: An Update

2003

Ifosfamide is an alkylating agent that is widely used in the treatment of various neoplasms, such as sarcomas, lymphomas, pediatric malignancies, germ cell tumors, lung, breast and ovarian cancer. The clinical toxicity of ifosfamide depends on the dose and administration schedules. The pharmacologic features of this drug enable its combination with other antiblastic agents, such as vinorelbine, gemcitabine, paclitaxel and docetaxel. Moreover, the pharmacologic profile of ifosfamide allows the use of this antiblastic drug in patients who have previously failed many other treatments, and a large percentage of responses has already been obtained. There is some concern about the optimal schedul…

Über die Hemmung der Arginase durch Stickstofflost

1952

Liver arginase is completely inhibited by nitrogen mustard [tris-(β-chloroethyl)amine, HCl] at a final concentration of 4.6×10−4 M. This holds true for isolated liver cell nuclei also. The experimental conditions are described exactly.

Acute cytotoxicity and apoptotic effects after l-Pam exposure in different cocultures of the proximal and distal respiratory system.

2009

Abstract Sulphur and nitrogen mustard are strong alkylating agents which can cause after inhalation acute lung injury in the larynx, trachea and large bronchi and can lead to alveolar edema. In our study we tested the N-Lost l -Phenylalanine Mustard ( l -Pam). Therefore we seeded the alveolar type II cell line NCI H441 on the upper membrane of a Transwell filter plate and the endothelial cell line ISO-Has-1 on the lower side of the membrane for the alveolar model and combined the human bronchial explant-outgrowth cells and fibroblasts in the bronchial model and exposed both models with various concentrations of l -Pam. Treatment with l -Pam led to a concentration-dependent decrease of the t…

Infrequent promoter methylation of the MGMT gene in liver metastases from uveal melanoma.

2008

Uveal melanoma is associated with a high mortality rate once metastases occur, with over >90% of metastatic patients dying within less than 1 year from metastases to the liver. The intraarterial hepatic (iah) administration of the alkylating agent fotemustine holds some promise with response rates of 36% and median survival of 15 months. Here, we investigated whether the DNA-repair-protein MGMT may be involved in the variability of response to fotemustine and temozolomide in uveal melanoma. Epigenetic inactivation of MGMT has been demonstrated to be a predictive marker for benefit from alkylating agent therapy in glioblastoma. We found a methylated MGMT promoter in 6% of liver metastases fr…

1981

New nitrogen mustard analogues in which bis(2-chloroethyl)-amino groups are separated by oxyethylene groups, 1,14-dichloro-3,12-bis(2-chloroethyl)-3,12-diaza-6,9-dioxatetradecan (3c) and 1,17-dichloro-3,15-bis(2-chloroethyl)-3,15-diaza-6,9,12-trioxaheptadecane (3d), were synthesized by reaction of bis(2-hydroxyethyl)amine (2) with bis(2-chloroethyoxy)ethylene (1a) and with 1,11-dichloro-3,6,9-trioxaundecane (1b), respectively, followed by treatment with thionyl chloride. The analogues were then complexed with heparin. The resulting heparin-complexes show inhibiting activity against transplanted Sarcoma-180 A in mice.