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At least 793 records · Page 44Linked to original sources
PubMed1983

Sequential non-cross-resistant chemotherapy regimens (MOPP and CAVmP) in Hodgkin's disease stage IIIB and IV.

Fifty consecutive patients with advanced Hodgkin's disease were treated in a multicentre study with 6 cycles of an alternating scheme of MOPP and CAVmP followed by irradiation to a dose of 20 Gy. The objective was to increase complete remission (CR) and cure rates by alternating two effective noncross-resistant regimens with subsequent consolidation of the remission by irradiating bulky nodes. A total of 47 patients completed the treatment and are evaluable. In the first 13 patients the irradiation fields amounted to a total or subtotal nodal irradiation with inclusion of the spleen. In case of organ involvement the affected organ was also included in the irradiation field. The irradiation protocol was later changed to an irradiation of the initially involved sites because of severe leucopenia and thrombopenia. After completion of the chemotherapy 32 (68%) patients (for Stage IIIB and IV patients: 63% and 71%, respectively) achieved a CR, after ending the radiotherapy the percentage of CR increased to 87% (for stage IIIB and IV patients: 90% and 86%, respectively). Five of the patients relapsed in an irradiated and nonirradiated area, three patients in a nonirradiated field. The actuarial 3-year survival rate for the entire group was 86% and for patients in CR 94%. The relapse-free survival was 73%. It is concluded that this alternating chemotherapy scheme followed by irradiation is at least equally effective as MOPP treatment in achieving a CR, and is probably superior in terms of survival.

Adolescent↗
PubMed1985

Combined radiation and chemotherapy for locally advanced transitional cell carcinoma of the urinary bladder.

A prospective study was performed on 22 patients with locally advanced transitional cell carcinoma of the urinary bladder to evaluate the toxicity and efficacy of an integrated treatment with cis-diamminedichloroplatinum (1.6 mg/kg body weight every 3 weeks for four cycles) and 60 G cobalt 60 or 18 MEV photons. Local and systemic toxicity caused by this treatment schedule was minor. Late sequelae consisted of contracted bladder in three patients. The rate of tumor-free bladders after a mean follow-up of 14 months was 17 of 22. Distant metastases occurred in three patients. Local recurrence of superficial tumor elsewhere in the bladder was observed in two patients. Six patients died 4 to 10 months after initiation of the integrated therapy, three of these without evidence of disease.

Aged↗
PubMed1984

Autologous marrow transplantation for patients with chronic myelogenous leukemia (CML) in blast crisis.

Even patients with chronic myelogenous leukemia (CML) in blast crisis were treated with chemotherapy, followed by infusion of autologous bone marrow that had been collected during the chronic phase of the disease and cryopreserved at -198 degrees C. The mean age of the nine females and two males in this study was 34 years with an average duration of the chronic phase of the disease of 5.5 years. Seven out of the 11 patients had a splenectomy prior to intensive chemotherapy. The median survival of the first four patients who received 6-thioguanine, cytosine arabinoside, daunorubicin (TAD) chemotherapy was 2.6 weeks and no patient reachieved the chronic phase of CML. The second group of seven patients received more intensive chemotherapy (MAdHAT), which included melphalan 30 mg/m2 days 1, 2, and 3; Adriamycin 50 mg/m2 intravenously (iv) day 1, hydroxyurea 1500 mg/m2 by mouth for 5-7 days, cytosine arabinoside 100 mg/m2 continuous infusion for 5-7 days, and VM-26 100 mg/m2 iv on day 3. Six out of these seven patients reachieved chronic phase CML after bone marrow reinfusion. The median survival was 29.9 weeks for all patients and 33 weeks for the six patients who reachieved chronic phase CML. All patients subsequently died of recurrent blast crisis. There was no correlation between the time of bone marrow storage and the duration of subsequent chronic phase CML. These studies have shown that autologous bone marrow transplantation after high-dose chemotherapy can result in bone marrow engraftment with reestablishment of chronic phase CML, and prolongation of survival.

Adult↗
PubMedDate not supplied

VIM3-ARA C: an effective salvage regimen in refractory or recurrent aggressive non Hodgkin's lymphoma. A report on 18 cases.

Based on encouraging results of previous combination regimens, we used a combination of VM26, ifosfamide, methyl GAG, mitoxantrone (or adriamycin), high-dose (HD) methotrexate and HD Ara C to treat 18 patients with relapsed or refractory NHL. Front-line therapy had been in most of them a reinforced CHOP regimen. Twelve patients (67 per cent) responded: there were nine (50 per cent) partial responses (PR) and three (17 per cent) complete remissions (CR). Nine of these 12 responders were grafted (eight autologous, one allogeneic transplants), one relapsed before autograft could be performed and the two remaining patients were excluded from autograft because of positive bone marrow. Five of nine patients remained free of disease after 11+ to 27+ months. Response rate was higher in patients who relapsed 'off' therapy (2/3), but CR was also obtained in two refractory NHL and persisted for 11+ and 26+ months, suggesting that VIM3-ARA C was, at least partially, non-cross-resistant with front-line adriamycin-containing regimens.

Adult↗
PubMed1989

Cytotoxicity mediated by tumor necrosis factor in variant subclones of the ME-180 cervical carcinoma line: modulation by specific inhibitors of DNA topoisomerase II.

The mechanism of tumor necrosis factor (TNF)-induced cytotoxicity has been investigated using two clonal variants of the ME-180 human cervical carcinoma cell line. The clonal lines were characterized with respect to their expression of TNF receptors, kinetics of cell death, and their ability to communicate intercellularly through gap junctions. The ME-180.4 and ME-180.8 clones were identified by their relative sensitivity to TNF induced lysis in a 24-h assay. The dose of TNF required to kill 50% of the target cells was 60 pM for the sensitive ME-180.4 and 2.5 nM for the ME-180.8. However, when assay times were extended, the dose response for both clones was the same, indicating that a difference in the kinetics of cell death and not absolute TNF sensitivity existed between the ME-180.4 and ME-180.8 clones. Both clones were gap junction deficient as judged by their inability to transfer Lucifer yellow or 6-carboxyfluorescein, a characteristic phenotype of cells sensitive to cytotoxicity by TNF. The level of surface receptor expressed on these clones was nearly identical with a Kd = 0.3 nM and 5,000 binding sites per cell. Measurement of the kinetics of cell death revealed that the time between the addition of TNF and the onset of observed cell death (induction phase) was much shorter for the ME-180.4 (32-55 h) than for the resistant ME-180.8 (55-80 h). Mitomycin C, a DNA alkylating agent, significantly reduced the length of the induction phase for both clones, although the kinetic difference between the clones remained unchanged. Two epipodophyllotoxins, VP-16 and VM-26, which specifically inhibit the rejoining activity of DNA topoisomerase II, showed a 10-100-fold synergistic effect when combined with TNF as shown by isobologram analysis. VM-26 when added to the resistant ME-180.8 clones decreased the length of induction phase and abolished the kinetic difference observed with the ME-180.4 clone. These results indicate that the variance in the TNF response of these two clones was closely associated with DNA topoisomerase II, and suggest that this enzyme may play an important role in TNF mediated cytotoxicity.

Cell Communication↗
PubMed1993

Resistance of mitochondrial DNA to degradation characterizes the apoptotic but not the necrotic mode of human leukemia cell death.

Cell death can occur by two basically different processes. The original term, necrosis, is now reserved for the generally destructive series of events which include the release of lysosomal enzymes and loss of cell membrane integrity. In contrast, mild treatment with cell damaging agents, or withdrawal of growth factors, may result in a characteristic form of degradation of cellular DNA which is associated with cell death that has morphology known as apoptosis. In this study human leukemia cells were exposed to agents or conditions previously reported to cause necrosis or apoptosis, monitored by detection of DNA "ladders," and the integrity of cellular DNA was determined on Southern blots. Nuclear DNA was distinguished from mitochondrial DNA by use of probes specific for nuclear genes or for mitochondrial DNA. When HL60, K562, MOLT4, or U937 cells were exposed to conditions which resulted in necrosis, mitochondrial DNA was damaged at approximately the same rate as nuclear DNA, but in apoptosis mtDNA was not degraded. Thus, the ratio of the relative (to untreated cells) abundance of mitochondrial DNA measured by a probe for 16S mitochondrial ribosomal RNA on Southern blots, to the relative abundance of DNA of any nuclear gene, was 1 or less in necrosis, but rose to values greater than 2 in apoptosis. It is concluded that the comparison of the degree of fragmentation of mitochondrial and nuclear DNA provides a quantitative way of distinguishing necrosis from apoptosis.

Apoptosis↗
PubMed1991

Induction of heat-shock response and alterations of protein phosphorylation by a novel topoisomerase II inhibitor, withangulatin A, in 9L rat brain tumor cells.

Withangulatin A is a newly identified in vitro topoisomerase II inhibitor isolated from the Chinese antitumor herb Physalis angulata. In vivo, it was found to be cytotoxic, capable of suppressing general protein synthesis and of inducing the synthesis of a small set of proteins including those generated by heat-shock treatment. The 70 kDa protein generated by withangulatin A was unequivocally identified as the heat-shock protein 70 (HSP70) since both proteins migrated to the same position on two-dimensional polyacrylamide gels, could be recognized by a monoclonal antibody to human HSP70, and exhibited identical peptide maps. The induction of protein synthesis by withangulatin A was regulated at the transcriptional level since it was aborted in cells pre-treated with actinomycin D. However, the initiation of this process did not require de novo protein synthesis since it was not affected by cycloheximide. Other cellular effect of withangulatin A was alterations of protein phosphorylation including an enhancement of phosphorylation of a 65 kDa protein which was also detected in the heat-shocked cells. Moreover, this process was observed within 7.5 min after the initial heat treatment which is much faster than the onset of HSP synthesis. Therefore, increased phosphorylation of the 65 kDa protein may represent one of the earliest signals generated by both heat-shock and withangluatin A and may be involved in the upstream regulation of heat-shock response in cells.

Animals↗
PubMed1978

Sequential and adjuvant chemotherapy for malignant astrocytoma of the brain.

Twenty-nine patients with grade III or IV astrocytomas were treated with 1,3 bis(2-chloroethyl)-1-nitrosourea (BCNU), 75--100 mg/M2 intravenously (IV) for two consecutive days every four to six weeks, in an effort to improve the quality and length of their survival following surgical resection. Twenty-one of these patients received adjunctive chemotherapy as soon as they recovered from surgery and 18 received concomitant adjunctive radiation therapy as well. Eight patients were treated with radiation therapy after surgery, and BCNU was not added until evidence of tumor growth appeared. BCNU was discontinued and the epipodophyllotoxin, VM-26, was given at a dose of 100 mg/M2 IV weekly when further tumor growth occurred. Patients receiving adjuvant chemotherapy had a shorter mean and median survival than patients receiving BCNU when progression appeared following radiation therapy. Six patients with progressive disease following surgical resection and radiation therapy for grade II astrocytoma were treated with BCNU. Improvement or stabilization of neurologic symptoms occurred in four of these patients. This trial of lower-dose BCNU therapy produced survival rates similar to higher-dose studies and permitted fewer physician visits by the patient.

Brain Neoplasms↗
PubMed1975

Combination chemotherapy based on a model of cell recruitment by partial synchronization.

A noncomparative, phase II clinical trial on chemotherapy of leukemias and solid tumors has been undertaken. It has been attempted: (a) to synchronize cells by a first administration of an M-dependent agent (vincristine or VM 26) which blocks them during the mitotic phase (M) (this has been verified by the mitotic index), from where they start again to go into the other phases of the cycle, more or less at the same time (this has been verified by the labeling index) and (b) to destroy a greater number of cells by a second administration of cycle-dependent or phase-dependent agent(s). Remarkable results have been obtained, the most interesting one being apparently complete remissions or regressions given by the sequence of two agents in patients who during previous trials proved to be resistent to both agents administered separately. The chemotherapy protocols thus composed are administered intermittently, comprising cycles with free intervals, the duration of which depends on the time of the bone marrow and blood restoration. The hematological, immunological, and visceral tolerance is, on the whole, satisfactory.

Drug Therapy, Combination↗
PubMed1982

VM-26 with prednisone and vincristine for treatment of refractory acute lymphocytic leukemia.

Fifty-six children with refractory acute lymphocytic leukemia (ALL) were assessed for remission-induction responses to VM-26 (250 mg/m2 per week) in combination with prednisone (40 mg/m2 per day) and vincristine (1.5 mg/m2 per week). Each child had been treated intensively with steroids, vincristine, daunorubicin and L-asparaginase. In fact, all patients had failed to respond to previous reinduction therapy with prednisone-vincristine or had relapsed while receiving vincristine. Our intent in this study was to test whether or not addition of VM-26 to prednisone-vincristine would overcome clinical resistance to these established agents. Complete remissions were induced in 17 patients (0.30) over 4 to 6 weeks. Five of these children, all clinically unresponsive to prednisone-vincristine alone, had complete remissions that lasted longer than 1 year; two remain in remission for 2 1/2 years and both are now off therapy. Myelosuppression, the most serious treatment complication, was documented in 20 of 26 evaluable patients. The median time to recovery of normal marrow function was 15 days. These results demonstrate further the potential of VM-26 in combined-drug treatment of refractory ALL. Whether the effectiveness of this combination represents potentiation of prednisone and vincristine activity by VM-26 or some other, as yet unidentified interaction, remains to be determined.

Adolescent↗
PubMed1988

High-dose methotrexate improves clinical outcome in children with acute lymphoblastic leukemia: St. Jude Total Therapy Study X.

High-dose methotrexate (HDMTX, 1,000 mg/m2) and cranial irradiation/sequential chemotherapy (RTSC) were compared for ability to extend complete remission durations in children with acute lymphoblastic leukemia (ALL). Three hundred thirty patients were enrolled in the study, according to our criteria for standard-risk ALL: a leukocyte count less than 100 X 10(9)/L, no mediastinal mass, no leukemic involvement of the central nervous system (CNS), and blast cells lacking sheep erythrocyte receptors and surface immunoglobulin. Prednisone-vincristine-asparaginase induced complete remissions in 95% of the patients, who were then randomized to receive either HDMTX (n = 154) or RTSC (n = 155). HDMTX was administered with intrathecal MTX for the first 3 weeks following remission induction, and then every 6 weeks with daily mercaptopurine (MP) and weekly oral MTX for a total of 18 months. The RTSC regimen consisted of 1,800 cGy cranial irradiation and intrathecal MTX for 3 weeks, followed by MP/MTX, cyclophosphamide/doxorubicin, and teniposide/cytarabine administered sequentially over 18 months. The final 12 months of treatment for both groups was MP and oral MTX; all patients received intrathecal MTX every 12 weeks. With a median follow-up of 5 years, complete remission durations have been significantly longer among children treated with HDMTX, compared with RTSC (P = .049) or historical institutional control regimens (P = .002). Approximately 67% of the patients receiving HDMTX and 56% of those receiving RTSC are expected to be in continuous complete remission at 4 years. Overall, isolated CNS relapse rates were similar (P = .17) in the two treatment groups, although by newer risk criteria cranial irradiation could be expected to provide better protection in patients with an unfavorable prognosis. These findings indicate that addition of intermittent HDMTX infusions to conventional chemotherapy is an effective method for extending complete remissions in children with ALL.

Child↗
PubMed1988

Deoxycoformycin treatment for childhood T-cell acute lymphoblastic leukemia early in second remission: a Pediatric Oncology Group Study.

2-Deoxycoformycin (DCF) was added to an intensive Pediatric Oncology Group protocol (#8303) for children with T-cell acute lymphoblastic leukemia or T-cell lymphoblastic lymphoma in first relapse. Twenty-seven patients received one or more courses of DCF at 15 mg/m2/day as a 3-day continuous infusion immediately after achieving a second remission with a four-drug reinduction regimen. Renal and neuromuscular toxicities were frequent and occasionally severe despite the provision of a source of adenosine deaminase by means of a packed red cell transfusion 1 day following the infusion of DCF. Hepatic toxicity, manifested by transaminase elevations, accompanied 62% of the courses. The median duration of the second complete remission was 4 months (range 2-16+ months), with only two of the 27 patients still in remission at 13+ and 16+ months. Plasma concentrations of deoxyadenosine (dAdo) and the ratio of red cell deoxyadenosine triphosphate to adenosine triphosphate (dATP:ATP) were measured prior to the DCF infusion and on day 4. A dATP:ATP ratio of 1.0 or greater was seen in two patients with acute renal failure. There was no apparent correlation between toxicity or response and the plasma dAdo concentrations. DCF administered according to this dose and schedule was excessively toxic and did not appreciably prolong the duration of the second complete remission in children with T-cell lymphoblastic malignancies.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1991

Treatment of stage IV-S neuroblastoma: a study of 34 cases treated between 1982 and 1987.

Between January 1982 and December 1987, of 283 children with neuroblastoma treated in the Pediatric Department of Institut Gustave Roussy, 34 were stage IV-S. Two groups were distinguished according to the initial clinical presentation: 16/34 patients had life-threatening symptoms and needed immediate treatment, and 18/34 had no life-threatening symptoms. Hepatic irradiation was used in 12/16 patients of the first group with respiratory distress. Chemotherapy was used in three patients. Of these 16 patients, three patients died of progressive disease (one patient died of a reason not related to the tumor). Twelve are alive in first complete remission and one in second complete remission. Of the 18 patients of the second group, eight had spontaneous complete remission, and one of them relapsed thereafter and died despite treatment. Ten patients needed treatment, radiotherapy, and/or chemotherapy depending on the site of disease progression. Two of them died of the disease. The overall disease-free survival for these 34 patients is 75% at 90 months postdiagnosis. Using this therapeutic strategy, it was possible to avoid any treatment of metastases in 25% of the patients.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1992

Neuroblastoma with intracranial involvement: an ENSG Study.

We report the experience of the European Neuroblastoma Study Group (ENSG) with central nervous system (CNS) involvement of neuroblastoma. Among this series of intensively treated patients, CNS neuroblastoma was diagnosed by computerised tomography (CT) scanning, rather than by autopsy. Cranial disease occurred in 5% of ENSG patients. Of 11 patients with intracranial disease, 4 had disease in the posterior fossa, a site rarely reported previously. Furthermore, 5 cases had CNS metastases at a time when there was no detectable disease elsewhere, rather than as part of extensive relapse. The pattern of disease we observed, at least for those with parenchymal disease, is in keeping with arterial spread. Although CT scanning is the optimal modality for identifying CNS disease, 2 cases had normal head CT scans prior to the onset of CNS disease. As most patients had symptoms of raised intracranial pressure (RICP) at the time the CNS disease was diagnosed, there does not seem to be any indication for routine CT scanning of the head at diagnosis, but this should be performed as soon as any symptoms or signs appear. With patients living longer with their disease, vigilance must be maintained during follow-up.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1993

Effective multi-agent chemotherapy for advanced abdominal lymphoma and FAB L3 leukemia of childhood.

Between June 1981 and May 1988, 51 children with diffuse undifferentiated, advanced (Murphy Stage III and IV) intra-abdominal non-Hodgkin's lymphoma were treated on an intensive multi-drug chemotherapy protocol without irradiation to the primary tumour. Therapy was completed for Stage III disease at one year, but Stage IV patients continued with a further year of therapy until January 1986, when it was reduced to one year. Central nervous system (CNS) prophylaxis consisted of eight doses of intrathecal MTX for all children, and 24 Gy cranial irradiation for Stage IV patients only. There were 42 patients with Stage III disease (III A n = 29 and III B n = 13) and nine patients with Stage IV disease, of whom eight had extensive bone marrow and extramedullary disease (FAB L3 ALL). No patient had CNS disease at presentation. Forty-eight of 51 children (94%) achieved a complete remission. Two children died during remission induction therapy and eleven children relapsed, mostly within eight months of diagnosis. All patients have completed therapy. Failure free survival is 76% for Stage III and 67% for Stage IV patients, with a median followup of 90 and 64 months, respectively. Subdividing Stage III patients into Stage III A and III B did not show significantly different survival (P = 0.9), but the number of patients in Stage III B is small. These results compare favourably with the most effective published protocols, and toxicity has been manageable.

Abdominal Neoplasms↗
PubMed1994

Successful treatment of acute lymphoblastic leukemia in a child with cystic fibrosis.

A 3 1/2 year old girl with cystic fibrosis who underwent successful treatment for acute lymphoblastic leukemia remains in complete remission 36 months after diagnosis. We also report high clearance rates of three antineoplastic agents in this patient. Drug doses were adjusted to achieve optimal systemic exposure.

Antineoplastic Combined Chemotherapy Protocols↗