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At least 1,243 records · Page 69Linked to original sources

Spin-labeled 1-alkyl-1-nitrosourea synergists of antitumor antibiotics.

A new method for synthesis of four spin-labeled structural analogues of the antitumor drug 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea (CCNU), using ethyl nitrite for nitrosation of the intermediate spin-labeled ureas has been described. In vitro synergistic effects of 1-ethyl-3-[4-(2,2,6,6-tetramethylpiperidine-1-oxyl)]-1-nitrosourea (3b) on the cytotoxicity of bleomycin and farmorubicin were found in human lymphoid leukemia tumor cells. We measured the tissue distribution of 3b in organ homogenates of C57BL mice by an electron paramagnetic resonance method. The spin-labeled nitrosourea was mainly localized in the lungs. Our results strongly support the development and validation of a new approach for synthesis of less toxic nitrosourea derivatives as potential synergists of antitumor drugs.

Animals↗

[Role of adjuvant chemotherapy in the treatment of medulloblastoma in children].

A retrospective review was carried out to evaluate the results of treatment (1989-1998) of 81 children, aged under 15, with primary medulloblastoma. Thirty-three patients received surgery and postoperative craniospinal radiotherapy; 48--adjuvant chemotherapy (VCR 1.5 mg/m2, i.v., 1 day; CCNU 75 mg/m2, per os, 1 day; cisplatin 80 mg/m2 or carboplatin 400 mg/m2, i.v., 1 day). Overall 9-year survival was 37 +/- 0.8%. This index in the adjuvant chemotherapy group was 59 +/- 0.8%, without chemotherapy--22 +/- 0.8%.

Adolescent↗

Phase II trials with procarbazine (NSC-77213), streptozotocin (NSC-85998), 6-THIOGUANINE (NSC-752), and CCNU (NSC-79037) in patients with metastatic cancer of the large bowel.

One hundred and ninety-seven patients with measurable metastatic cancer of the colon have been treated with one of four anticancer drugs which have had little prior trial in this disease. Objective tumor responses lasting a median of 9 weeks occurred with 0.5 g/m of streptozotocin given intravenously every week (10 percent), 130 mg/m of CCNU given orally every 6 weeks (10%), 1.0 mg/kg/day of 6-thioguanine given orally (8%), and 3 mg/kg/day of procarbazine given orally (3%). Performance status declined more rapidly with streptozotocin and 6-thioguanine and the median survival time was less (12 and 16 weeks respectively) than with procarbazine and CCNU (23 and 20 weeks respectively). This study suggests that procarbazine given in this way is ineffective but trials of streptozotocin or 6-thioguanine combined with other agents active against colon cancer should ensue as well as further exploration of the usefulness of other nitrosoureas.

Clinical Trials as Topic↗

A comparison of the lethal effects of three nitrosourea derivatives on cultured human lymphoma cells.

The cellular effects of three nitrosourea derivatives were investigated on a human lymphoma cell line. The three drugs show similar threshold-type dose-response survival curves on asynchronous cells treated for 1 hr. Longer incubation periods result in rapid biological degradation for 1,3-bis(2-chloroethyl)-1-nitrosourea and 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea, whereas, 1-(2-chloroethyl)-3-trans-4-methylcyclohexyl)-1-nitrosourea, remains cytotoxic after about 24 hr. Important differences were noted with respect to cell cycle dependency. The 1,3-bis(2-chloroethyl)-1-nitrosourea was more effective in early S and in G2 phase, whereas both 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea and 1-(2-chloroethyl)-3-trans-4-methylcyclohexyl)-1-nitrosourea were more effective in early S. 1,3-bis(2-chlrorethyl)-1-nitrosourea exerted a considerable degree of killing in G1. Cells were unable to recover from priming damage induced by all 3 nitrosourea derivatives. No synergistic effects were observed in combination with vitamin A.

Amphotericin B↗

[Recurrence of Hodgkin's disease after advanced primary stages. German Hodgkin's Study Group].

In a multicentre study on the treatment of Hodgkin's disease, 88 out of 297 patients with primary advanced stages IIIB/IV failed to respond to alternating COPP/ABVD chemotherapy +/- radiotherapy. They may be broken down as follows: tumour progression under current therapy (PD) 23/28, partial remission at the end of treatment (PR) 28/88, early nodal recurrence 13/88, late nodal recurrence 15/88, extranodal recurrence 7/88, unclear localisation 1/88. Thirty-six months after noting failure of treatment, 45% of all patients were still alive. The prognosis was poorest in the case of primary PD. Only 1/23 of these patients experience lasting complete remission thanks to salvage treatment (cCR). Eleven patients with an exclusively nodal recurrence experienced a cCR on treatment with radiation alone, and may be considered a low-risk recurrence group. For a high-risk recurrence group (n = 57), indication for high-dose chemotherapy with subsequent autologous bone marrow transplantation (HDC/ABMT) should have been recognized on the basis of the present definition. The survival probability of these patients, who only received conventional salvage treatment, was 38% after 30 months (95% confidence limit, 22 to 54%). These data would not appear to be appreciably poorer than those reported in the literature for comparable patients receiving HDC/ABMT. Only a randomized comparison would be capable of showing whether HDC/ABMT is superior to high-dose conventional chemotherapy with haematopoietic growth factors. It is proposed that such a therapeutic trial should be initiated as soon as possible.

Adolescent↗

[Occurrence of an epidermoid bronchial carcinoma 8 years after a small cell carcinoma treated with only 3 courses of chemotherapy].

A case of squamous cell bronchial carcinoma developed 8 years after treatment of a small cell carcinoma is reported. Three hypotheses may be put forward to explain this sequence of events: either a squamous cell line was selected from within an initially mixed tumour, or the small cell carcinoma differentiated into a squamous cell carcinoma, or a second primary tumour developed independently. All this is purely speculative, but the long doubling time implied by the first two hypotheses would be in favour of a second primary tumour.

Antineoplastic Combined Chemotherapy Protocols↗

Brain calcifications and dementia in children treated with radiotherapy and intrathecal methotrexate.

In the last five years we observed 8 young patients aged under 15 years, in whom the basal ganglia were calcified after application of methotrexate and/or radiotherapy for treatment of a brain or cerebellar tumor. In both patients leukoencephalopathy was evident besides calcification of the basal ganglia and, in one, the ventricles were enlarged and he had also signs of cerebral and cerebellar atrophy. In the production of leukoencephalopathies and calcifications by chemo- and radiotherapy, the age is a very important factor. In adult patients it is exceptional to see them. Brain immaturity is probably associated with the presence of leukoencephalopathy and intracranial calcifications.

Antineoplastic Combined Chemotherapy Protocols↗