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At least 127 records · Page 7Linked to original sources
PubMed1984

Tumours from a cell strain with a high content of metallothionein show enhanced resistance against cis-dichlorodiammineplatinum.

Cultured cells with a high content of the extremely cysteine-rich protein metallothionein (MT) have previously been shown to exhibit resistance when exposed to otherwise lethal doses of cis-dichlorodiammineplatinum (cis-DDP), chlorambucil or prednimustine, and to have a significant proportion of intracellular drug associated with MT after such treatment. In order to study this protective mechanism in vivo, cells from a MT-rich variant of a murine fibroblast line resistant to cis-DDP and its parent sensitive line with only trace amounts of MT, were injected subcutaneously into nude mice (24 animals in each group), and tumour growth was compared during cis-DDP treatment. Animals in the treatment groups received 3 intravenous doses of either 4 mg/kg or 8 mg/kg of cis-DDP on day 12, 26 and 33 after inoculation of cells, whereas the control groups received saline. The 8 mg/kg dose produced an almost complete growth inhibition of the tumours derived from the parent cells, as well as from the MT-rich variant. However, following the injections with 4 mg/kg of cis-DDP, tumour volume was reduced by approximately 80% in tumours from the parent cells, whereas the tumours from MT-rich cells were almost completely resistant. This study provides for the first time evidence that metallothionein-conferred protection against cis-DDP toxicity also is mediated in tumours in vivo.

Animals↗
PubMed1985

In vitro activity of alkylating agents on human tumors as measured by a short-term antimetabolic assay.

The activity of some alkylating agents widely used in clinical practice was studied by an in vitro antimetabolic assay, which evaluates the interference of drugs on the incorporation of 3H-thymidine and 3H-uridine in short-term cultures of human tumors. The effect of CCNU, chlorambucil, cisplatin, melphalan, prednimustine, procarbazine and the pro-active derivatives of cyclophosphamide and ifosfamide, 4-hydroperoxycyclophosphamide and 4-hydroperoxyifosfamide, was tested on non-Hodgkin lymphomas, germ cell testicular tumors, breast and ovarian cancers. Similar effects were generally produced by the drugs on both DNA and RNA precursor incorporation, and the in vitro response rates were similar to those clinically obtained for the same tumor types by using the same drugs in monochemotherapy. The effects of different alkylating agents on the individual tumors were not significantly associated, except for the analogues 4-hydroperoxycyclophosphamide and 4-hydroperoxyifosfamide, for which a significant agreement rate was observed. No evidence of acquired resistance to 4-hydroperoxycyclophosphamide and cisplatin after clinical treatment with the same drug was found in samples from ovarian cancer and non-Hodgkin lymphoma, but there was a definite trend in germ cell testicular tumors to lower sensitivity to cisplatin in previously treated patients.

Alkylating Agents↗
PubMed1991

Nine years' experience with ABMT in 128 patients with Hodgkin's disease: an Italian study group report.

One-hundred, twenty-eight patients with Hodgkin's disease in remission or who had failed a mechlorethamine, vincristine, procarbazine and prednisone (MOPP), a doxorubicin, bleomycin, vinblastine and dacarbazine (ABVD) and/or lomustine, etoposide and prednimustine (CEP) regimens have been treated with a high-dose therapy (HDT) containing cyclophosphamide, etoposide, carmustine (CVB) and autologous bone marrow transplantation (ABMT). Forty patients were treated while they were in resistant or progressive disease states using alternating MOPP/ABVD protocol; 15 patients received ABMT in first relapse; 51 patients had a complete remission (CR) with first-line therapy but later relapsed and then received conventional salvage therapy; 16 achieved no response or progression ("resistant relapse" patients) and 35 responded partially or completely ("sensitive-relapse" patients). The other 22 patients received ABMT in remission. Following HDT, 56 patients (52.8%) achieved CR and 23 patients (21.6%) achieved a partial remission for an overall response rate of 74.4%. Sixteen patients failed to respond and died in progressive disease 1 to 10 months (median 6 months) after ABMT. High-dose therapy produced severe toxicity including vomiting (100%), mucositis (75%) and liver enzymes and alkaline phosphatase elevations (51%). There were 10 treatment-related deaths. A multivariate analysis identified poor performance status and resistant-relapse patients as very important adverse risk factors for survival immediately after ABMT. These results, while validating this procedure for inducing remissions in advanced highly-treated patients, at the same time confirm the need of employing this approach in first relapse or in second complete remission after standard therapy and before ABMT or, in first complete remission in very high risk Hodgkin's disease patients. Our experience in 15 very poor prognosis Hodgkin's disease patients transplanted in first CR demonstrated to be much significant.

Adult↗
PubMed1991

Strategies of reducing the carcinogenic risk of cytostatic agents on the basis of bioassay evaluation.

This article described strategies that can be used to reduce the carcinogenic risk of cytostatic chemotherapy and summarizes our recent experimental results. Reduction of neoplasms caused by the carcinogenic potency inherent in cytostatic agents can be obtained. (A) by chemical modifications such as: (1) exchanging a chlorine atom in N, N'-bis-(2-chloroethyl)-N-nitrosourea (BCNU) in the chloroethyl group at N'-position for a hydroxyl group to form the less carcinogenic analog N-(2-chloroethyl)-N'-(2-hydroxyethyl)-N-nitrosourea (HECNU); (2) linking chlorambucil to the steroid prednisolone to obtain a conjugate (prednimustine) with distinctly lower carcinogenic potential than chlorambucil; (3) progressive ring halogenation of phenyl-triazenes to generate agents with decreased long-term toxic risk; (B) by replacing cyclophosphamide within the carcinogenic drug combination of cyclophosphamide, methotrexate and 5-fluorouracil (CMF) by vincristine to form the combination VMF which has no detectable carcinogenic potential; (C) by coadministration of cyclophosphamide and mesna to achieve a dose-related reduction of cyclophosphamide-induced urinary bladder carcinomas; (D) by administration of dinaline, a compound which reduces the spontaneous incidence of malignant tumors in rats. These examples demonstrate that the carcinogenic risk of single agents and drug combinations used for antineoplastic chemotherapy has successfully been reduced, as assessed in long-term bioassays. Such strategies should be considered in the treatment of patients with long life expectancy following cytotoxic chemotherapy.

Animals↗
PubMed1990

Prediction of the cytotoxic effects of some antineoplastic drugs on cultured T-lymphoma cells by microcalorimetry.

The effects on T-lymphoma cells of the antineoplastic drugs Ara-C, cisplatin, vinblastine, chlorambucil and prednimustine were studied by microcalorimetry and a conventional viability assay. The heat production rate for cells was measured immediately after drug treatment and was compared with the change in cell concentration during the following generation time. The results of the microcalorimetric observations were correlated with cell death. Such correlations varied considerably for the different drugs, in particular between chlorambucil and the other drugs investigated.

Antineoplastic Agents↗
PubMedDate not supplied

Prolymphocytic leukemia with suppressor T-cell phenotype: report of two cases.

The clinical course of two patients with prolymphocytic leukemia of the suppressor T-cell phenotype is presented. Diagnosis was established by specific monoclonal antibody tests, cytochemical, ultrastructural and cytogenetic studies. The bone marrow showed a diffuse infiltration with medium sized lymphocytes displaying a prominent nucleolus. Both patients presented with pronounced splenomegaly, diffuse lymphnode involvement, leukocytosis, thrombocytopenia and anemia. One of them was refractory to chemotherapy using CHOP, Asparaginase, IMVP16, and irradiation to the spleen. He benefited from prednimustin and repeated leukaphereses, without reaching complete remission (C.R.). The second patient achieved a C.R. of 4 months duration with CHOP-Bleomycin. Survival was 16 and 11 months respectively.

Female↗
PubMedDate not supplied

Mitoxantrone: mechanism of action, antitumor activity, pharmacokinetics, efficacy in the treatment of solid tumors and lymphomas, and toxicity.

Mitoxantrone is similar to Adriblastin in its mechanism of action and antitumor activity. Objective remissions were obtained in 20-30% pretreated patients and in 23-44% of untreated patients by single-drug treatment of patients suffering from metastatic breast cancer. The objective response rates to Mitoxantrone in combination with CTX, 5-FU, MTX, VCR, MMC. Prednimustine or Vindesine were 16-46% in treatment and 38-89% in primary treatment. Randomized studies comparing Mitoxantrone with Adriblastin in single-drug and combination treatment did not show any significant differences in efficacy. However, Mitoxantrone was significantly less toxic. Remission rates of between 24 and 54% were achieved by single-drug treatment in pretreated patients suffering from non-Hodgkin lymphoma. Mitoxantrone appears to be active in ovarian cancer, lung cancer and hepatocellular carcinoma.

Animals↗
PubMed1980

The chemotherapy of prostatic carcinoma.

Results of the first randomized trial of the National Prostatic Cancer Project (NPCP) revealed an advantage for cytoxan and 5-FU over standard therapy in hormonally resistant stage D prostate carcinoma. A subsequent trial for patients previously irradiated, receiving the less myelosuppressive agents estracyt or streptozotocin also revealed an advantage over standard therapy. Other completed randomized trials have revealed activity for prednimustine and DTIC. Trials underway for newly diagnosed stage D disease or for stage D disease clinically stable to diethylstilbestrol (DES) show promising activity for cytoxan and DES combined. Current randomized trials in advanced disease are comparing methyl CCNU and hydroxyurea wih cytoxan, and estracyt or vincristine alone or in combination. Chemotherapy in earlier staged patients as adjuvants to definitive surgery or irradiation is underway in two trials, comparing the effects of cytoxan or estracyt as long-term therapies with no additional treatment.

Antineoplastic Agents↗
PubMed1990

Salvage chemotherapy in Hodgkin's disease. Results in patients relapsing more than twelve months after first complete remission.

Forty-nine patients with Hodgkin's disease who relapsed after a first complete remission of more than 12 months following primary chemotherapy were treated with salvage therapy regimens. A total of 41 patients (84%) achieved complete remission. In particular, complete response was documented in 17 of 19 patients re-treated with the same initial drug combination. The five-year freedom from progression, relapse-free and overall survivals were 51%, 57% and 65%, respectively. In our experience, consolidation radiotherapy following drug-induced remission failed to improve the five-year relapse-free survival. Present findings indicate that about half of patients relapsing after a disease-free interval exceeding 12 months can remain alive and disease-free 5 years after starting salvage chemotherapy.

Adult↗
PubMed1991

Surgical restaging of advanced Hodgkin's disease after first line chemotherapy.

47 patients with stages IIIB and IV Hodgkin's disease underwent laparotomy with splenectomy as restaging procedure after first-line chemotherapy (CT) which included 4 cycles of CT ABV/IMEP/PCAV/ABV. After surgical restaging (SR), all patients were scheduled to receive 2 additional cycles IMEP/PCAV followed by TNI 20 Gy and patients with residual clinical abnormality or positive restaging surgery received a 20 Gy boost to these areas. 11 patients (23.4%) were found to have active disease in the spleen (10 patients) and/or the lymph nodes (3 patients) after SR. In the spleen, foci of active disease had a size in millimeters and confirm the limits of clinical restaging. According to the response to CT, 5 of the 35 patients (14%) clinically restaged as good responders had active disease; 6 of the 12 patients (50%) clinically restaged as poor responders had active disease. SR is of interest in selected patients with slowly responding disease to determine the indication of an extended field RT for responding patients and salvage therapy for patients resistant to CT.

Adult↗
PubMed1989

Vindesine-epirubicin versus vindesine-mitoxantrone in metastatic breast cancer.

UNLABELLED: The present study was designed to assess the toxicity and efficacy of two chemotherapy protocols in patients with metastatic breast cancer. Starting in December 1985, 230 patients were randomized to receive vindesine (V) (3 mg/m2 i.v.) and mitoxantrone (M) (10 mg/m2 i.v.) or V and epirubicin (E) (40 mg/m2 i.v.) every 3 weeks x 3 and every 4 weeks thereafter. Patients were stratified according to site of disease (visceral, bone or soft tissue dominant) and prior therapy. Patient groups were comparable with respect to menopausal status, age, estrogen receptor status and disease-free interval. About two-thirds of the patients presented with visceral recurrence and 30% with bone lesions: only 8% had soft tissue metastases. RESULTS: We observed a significant difference (p = 0.003) in the frequency of alopecia (WHO grade 3-4, 36% vs. 60% favoring regimen VM); gastrointestinal and hematologic side effects and neurotoxicity were mild and similar for both groups. In 182 evaluable patients there was a 26% response rate (CR + PR. UICC criteria) for VM and 35% for VE (not significant). NC was observed in 37% and 43% of patients treated with VM or VE respectively. There was no significant difference between these two groups with regard to time to progression and survival. The median time of follow-up was 8 months and therefore too short to draw definite conclusions. Both regimens were well tolerated and seem to be equally effective, although the response rate for VM and VE was lower than expected.

Adult↗
PubMed1988

High-dose chemotherapy with autologous bone marrow transplantation in 50 advanced resistant Hodgkin's disease patients: an Italian study group report.

Fifty patients with recurrent Hodgkin's disease have been treated with high-dose therapy followed by autologous bone marrow transplantation. Forty-one patients had extranodal sites of relapse and 31 patients had constitutional symptoms. Two patients had been treated with mechlorethamine, vincristine, procarbazine, and prednisone (MOPP), lomustine, vinblastine, procarbazine, and prednisone (CcVPP), and radiation; 16 patients with MOPP, doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD), radiation, and lomustine, etoposide, and prednisone (CEP); 20 patients with alternating MOPP/ABVD, and 12 patients with alternating MOPP/ABVD followed by CEP and radiation. Eighteen patients had progressive disease during alternating MOPP/ABVD protocol alone or during conventional salvage therapy; 32 patients had had a complete remission with first-line therapy but later relapsed, 25 of them having received conventional salvage therapy; 12 achieved no response or progression ("resistant-relapse" patients); and 13 responded partially or completely ("sensitive-relapse" patients). Complete remission occurred in 24 patients (48%) with a median duration of 24 months and 16 patients (32%) achieved partial response with a median duration of 9 months, for an overall response rate of 80%. Ten patients failed to respond and died in progressive disease 1 to 10 months (median, 6 months) after transplantation. Toxicity was significant including infections (20%), liver enzymes and alkaline phosphatase elevations (100%), and carmustine lung toxicity (7%). There were two treatment-related deaths; one patient died of Pseudomonas aeruginosa septicemia and another patient died of cerebral hemorrhage. These results validate the procedure of high-dose therapy followed by autologous bone marrow transplantation in inducing remission in these advanced, highly-treated patients. Clearly, the question of whether high-dose therapy and transplantation will eventually supersede new conventional salvage therapies will be addressed after controlled clinical studies.

Adult↗
PubMed1986

Alternating non-cross-resistant combination chemotherapy or MOPP in stage IV Hodgkin's disease. A report of 8-year results.

In patients with stage IV Hodgkin's disease mechlorethamine, vincristine, procarbazine, and prednisone (MOPP) was randomly tested against MOPP alternated monthly with doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD). All 88 evaluable patients had not received chemotherapy and 25 had had a relapse after primary irradiation. The complete remission rate with MOPP/ABVD was 88.9% (40 of 45 patients), and with MOPP, 74.4% (32 of 43 patients). The 8-year results show that MOPP/ABVD was superior to MOPP in terms of freedom from progression (64.6% compared to 35.9%; p less than 0.005), relapse-free survival (72.6% compared to 45.1%; p less than 0.01), total survival (83.9% compared to 63.9%; p less than 0.06), and survival of complete responders (94.8% compared to 77.1%; p = 0.04). The delivery of MOPP/ABVD was not associated with an increased incidence of major toxicity. The early sequential rotation of two equally effective and non-cross-resistant drug combinations can substantially improve the likelihood of cure in patients with Hodgkin's disease.

Adolescent↗
PubMed1980

The chemotherapy of prostatic adenocarcinoma.

A number of chemotherapeutic agents show moderate promise for the palliative treatment of metastatic prostatic carcinoma. Although patterns of metastatic disease make classic response rates difficult to obtain and interpret, doxorubicin, cyclophosphamide, dacarbazine (DTIC), and cisplatin have activity in patients who have failed conventional hormonal treatment. In most studies, a survival advantage is seen for responders to these and other chemotherapeutic agents, but no survival advantage has been seen for the treatment cohorts when compared to groups not receiving chemotherapy. Therefore, estimates of the usefulness of these agents must be considered tentative. Multiple drug therapy has not yet shown definite superiority to single agent treatment. The uses and limitations of acid phosphatase as a tumor marker, as well as particular difficulties in measuring tumor response in the disease, are detailed herein.

Acid Phosphatase↗