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Magyar Onkologia Dec 2017The present review about the history of anticancer drug research in Hungary intends to call attention to the importance of studies on their mode of action. Several lines... (Review)
Review
The present review about the history of anticancer drug research in Hungary intends to call attention to the importance of studies on their mode of action. Several lines of evidence suggest that clinically usable oncopharmacological properties could be revealed by this way. Among the numerous compounds certain alkylating sugar alcohols and 2'-deoxyuridine derivatives were submitted to detailed investigations concerning their mode of action. Myelobromol with selective action on the myeloid elements of bone marrow has been justified for its application in chronic myeloid leukemia therapy and also in bone marrow ablation before transplantation. Mitolactol is able to cross bloodbrain barrier, consequently could control certain brain tumors. 5-etil-2'-deoxyuridine by reducing dihydropyrimidine dehydrogenase activity is able to increase 5-fluorouracil concentration in the blood, resulting in improved antitumor effect. In contrast, 5-hexil-2'-deoxyuridine, as an inhibitor of glycoconjugate pathway by reducing heparan sulfate production, has the ability to prevent metastasis. Noteworthy, the remarkable effects of vinca alkaloids, antiestrogens, and GNRH analogues were also presented in this review.
Topics: Antineoplastic Agents, Alkylating; Databases, Factual; Drug Design; Forecasting; Humans; Hungary; Mannomustine; Mitobronitol; Mitolactol; Pharmaceutical Research; Pharmacology, Clinical; Quality Improvement; Retrospective Studies
PubMed: 29257158
DOI: No ID Found -
British Medical Journal (Clinical... Jul 1983
Topics: Alkylating Agents; Altretamine; Antibiotics, Antineoplastic; Antimetabolites, Antineoplastic; Antineoplastic Agents; Cisplatin; Etoposide; Humans; Mitobronitol; Mitolactol; Nitrosourea Compounds; Razoxane; Vinca Alkaloids
PubMed: 6407699
DOI: 10.1136/bmj.287.6385.110 -
Oncotarget Oct 2016Different chemotherapy drugs are generally introduced in clinical practices combining with therapy for glioma treatment. However, these chemotherapy drugs have rarely... (Meta-Analysis)
Meta-Analysis
A network meta-analysis: the overall and progression-free survival of glioma patients treated by different chemotherapeutic interventions combined with radiation therapy (RT).
Different chemotherapy drugs are generally introduced in clinical practices combining with therapy for glioma treatment. However, these chemotherapy drugs have rarely been compared with each other and the optimum drug still remains to be proved. In this research, medical databases were consulted, PubMed, Embase and Cochrane Library included. As primary outcomes, hazard ratio (HR) of overall survival (OS) and progression-free survival (PFS) with their corresponding 95% credential intervals (CrI) were reported. A network meta-analysis was conducted; the surface under the cumulative ranking curve (SUCRA) was utilized for treatment rank and a cluster analysis based on SUCRA values was performed. This research includes 14 trials with 3,681 subjects and eight interventions. In terms of network meta-analysis, placebo was proved to be inferior to the combination of temozolomide (TMZ), nimustine (ACNU) and cisplatin (CDDP). Also, bevacizumab (BEV) in conjunction with TMZ were significantly more effective than placebo with an HR of 0.40. The estimated probabilities from SUCRA verified the above outcomes, confirming that the combination of TMZ, ACNU and CDDP exhibited the highest ranking probability of 0.889 with respect to OS, while BEV in combination with TMZ - with a probability of 0.772 - ranked the first place with respect to PFS. According to the results of this network meta-analysis, the combination of (1) TMZ, ACNU and CDDP; (2) BEV in combination with TMZ and (3) cilengitide in combination with TMZ, are considered as the preferable choices of chemotherapy drugs for glioma treatment.
Topics: Antibodies, Monoclonal, Humanized; Antineoplastic Agents; Bayes Theorem; Bevacizumab; Brain Neoplasms; Chemoradiotherapy; Cisplatin; Dacarbazine; Disease-Free Survival; Eflornithine; Glioma; Humans; Mitolactol; Network Meta-Analysis; Nimustine; Probability; Randomized Controlled Trials as Topic; Snake Venoms; Temozolomide; Treatment Outcome; Vincristine
PubMed: 27458167
DOI: 10.18632/oncotarget.10763 -
Pathology Oncology Research : POR 2000In recent years, there has been a dramatic increase in the number of tumors of the head and neck. Their successful treatment is one of the greatest challenges for... (Review)
Review
In recent years, there has been a dramatic increase in the number of tumors of the head and neck. Their successful treatment is one of the greatest challenges for physicians dealing with oncotherapy. An organic part of the complex therapy is preoperative or postoperative irradiation. Application of this is accompanied by a lower risk of recurrences, and by a higher proportion of cured patients. Unfortunately, irradiation also has a disadvantage: the development of osteoradionecrosis, a special form of osteomyelitis, in some patients (mainly in those cases where irradiation occurs after bone resection or after partial removal of the periosteum). Once the clinical picture of this irradiation complication has developed, its treatment is very difficult. A significant result or complete freedom from complaints can be attained only rarely. Attention must therefore be focussed primarily on prevention, and the oral surgeon, the oncoradiologist and the patient too can all do much to help prevent the occurrence of osteoradionecrosis. Through coupling of an up-to-date, functional surgical attitude with knowledge relating to modern radiology and radiation physics, the way may be opened to forestall this complication that is so difficult to cure.
Topics: Antineoplastic Agents, Alkylating; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Carcinoma, Squamous Cell; Cisplatin; Combined Modality Therapy; Cutaneous Fistula; Fistula; Humans; Jaw; Jaw Diseases; Male; Methotrexate; Middle Aged; Mitolactol; Mouth Neoplasms; Oral Hygiene; Orthognathic Surgical Procedures; Osteoradionecrosis; Osteotomy; Postoperative Complications; Premedication; Radioisotope Teletherapy; Radiotherapy; Scattering, Radiation; Surgery, Plastic; Surgical Flaps; Tomography, X-Ray Computed; Tongue Neoplasms; Tooth Diseases; Tooth Extraction; Vincristine; Wound Healing
PubMed: 10749589
DOI: 10.1007/BF03032659 -
Anticancer Research 2004This prospective semi-randomized study was undertaken to assess the effects and effectiveness of alkylating drugs in a preoperative setting. (Clinical Trial)
Clinical Trial Comparative Study Randomized Controlled Trial
BACKGROUND
This prospective semi-randomized study was undertaken to assess the effects and effectiveness of alkylating drugs in a preoperative setting.
PATIENTS AND METHODS
During a 6-year period preceding February 2000, 80 patients with Stage II-IVa (AJCC 2002) squamous cell cancer of the oral cavity were treated. Thirty patients (Group N) received a combination of bleomycin, vincristine and methotrexate (BVM). In the alkylating group, thirty patients (Group A/M) received BVM and mitolactol (dibromodulcitol), while twenty patients (Group A/C) received BVM and cisplatin. Patients underwent surgery within 3 weeks after chemotherapy. Clinical response rate and tumour-free survival were investigated.
RESULTS
Clinical complete response was 30%-36% (Group N-A). Partial response was 57%-56% (Group N-A). Side-effects were moderate and reversible. Nausea, anaemia and leucopenia were observed in the alkylating (A) group, while other side-effects (alopecia, mucositis, gastritis) were similar in both groups. The observation time was 36 months. Regional disease-free survival showed a significant difference, favouring the non-alkylating (N) group (p=0.03). A higher metastasis rate was observed in the alkylating (A) group.
CONCLUSION
Cisplatin and mitolactol in combination with BVM showed higher local control and lower disease-free survival than BVM alone. That was mostly due to a higher rate of regional metastatis formation in the alkylating-treated patients. This may be a late side-effect caused by the immunosuppressive and myelosuppressive effect of alkylating agents.
Topics: Antineoplastic Agents, Alkylating; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Carcinoma, Squamous Cell; Cisplatin; Disease-Free Survival; Female; Humans; Male; Methotrexate; Middle Aged; Mitolactol; Oropharyngeal Neoplasms; Prospective Studies; Treatment Failure; Vincristine
PubMed: 15330214
DOI: No ID Found -
Journal of Neuro-oncology Oct 2010To report long-term results for children with low-grade hypothalamic/chiasmatic gliomas treated on a phase II chemotherapy protocol. Between 1984 and 1992, 33 children...
To report long-term results for children with low-grade hypothalamic/chiasmatic gliomas treated on a phase II chemotherapy protocol. Between 1984 and 1992, 33 children with hypothalamic/chiasmatic LGGs received TPDCV chemotherapy on a phase II prospective trial. Median age was 3.0 years (range 0.3-16.2). Twelve patients (36%) underwent STRs, 14 (42%) biopsy only, and seven (21%) no surgery. Twenty patients (61%) had pathologic JPAs, nine (27%) grade II gliomas, and four (12%) no surgical sampling. Median f/u for surviving patients was 15.2 years (range 5.3-20.7); 20 of the 23 surviving patients had 14 or more years of follow-up. Fifteen-year PFS and OS were 23.4 and 71.2%, respectively. Twenty-five patients progressed, of whom 13 are NED, two are AWD, and 10 have died. All children who died were diagnosed and first treated at age three or younger. Age at diagnosis was significantly associated with relapse and survival (P = 0.004 for PFS and P = 0.037 for OS). No PFS or OS benefit was seen with STR versus biopsy/no sampling (P = 0.58 for PFS, P = 0.59 for OS). For patients with JPAs and WHO grade II tumors, the 15-year PFS was 18.8 and 22.2% (P = 0.95) and 15-year OS was 73.7 and 55.6% (P = 0.17), respectively. Upfront TPDCV for children with hypothalamic/chiasmatic LGGs resulted in 15-year OS of 71.2% and 15-year PFS of 23.4%. No survival benefit is demonstrated for greater extent of resection. Age is a significant prognostic factor for progression and survival.
Topics: Adolescent; Age Factors; Antineoplastic Combined Chemotherapy Protocols; Child; Child, Preschool; Disease Progression; Disease-Free Survival; Female; Glioma; Humans; Hypothalamic Neoplasms; Infant; Lomustine; Longitudinal Studies; Male; Mitolactol; Predictive Value of Tests; Procarbazine; Retrospective Studies; Salvage Therapy; Thioguanine; Treatment Outcome; Vincristine
PubMed: 20221671
DOI: 10.1007/s11060-010-0151-7 -
Blood Feb 2006Relapse is a major obstacle in the cure of acute myeloid leukemia (AML). The Pediatric Oncology Group AML Study 9421 tested 2 different strategies to improve event-free... (Randomized Controlled Trial)
Randomized Controlled Trial
Relapse is a major obstacle in the cure of acute myeloid leukemia (AML). The Pediatric Oncology Group AML Study 9421 tested 2 different strategies to improve event-free survival (EFS) and overall survival (OS). Patients were randomized to receive standard-dose DAT (daunorubicin, cytarabine, and thioguanine) or high-dose DAT during induction. To interfere with P-glycoprotein (P-gp)-dependent drug efflux, the second randomization tested the benefit of cyclosporine (CsA) added to consolidation chemotherapy. Of the 282 children randomly assigned to receive standard DAT induction, 248 (87.9%) achieved remission compared to 253 (91%) of the 278 receiving high-dose DAT (P = ns). Children with HLA-identical sibling donors who achieved a complete remission received an allogeneic bone marrow transplant as consolidation. For the 83 patients receiving a matched related donor bone marrow transplantation (BMT), the 3-year disease-free survival (DFS) is 67%. Of the 418 children who achieved remission and went on to consolidation with and without CsA, the DFS was 40.6% and 33.9%, respectively (P = .24). Overexpression of P-gp was infrequent (14%) in this pediatric population. In this study, intensifying induction with high-dose DAT and the addition of CsA to consolidation chemotherapy did not prolong the durations of remission or improve overall survival for children with AML.
Topics: ATP Binding Cassette Transporter, Subfamily B, Member 1; Antineoplastic Combined Chemotherapy Protocols; Child; Child, Preschool; Cyclosporine; Disease-Free Survival; Doxorubicin; Female; Humans; Immunosuppressive Agents; Infant; Karyotyping; Leukemia, Myeloid, Acute; Leukocyte Count; Male; Mitolactol; Remission Induction; Survival Analysis; Tamoxifen; Treatment Outcome
PubMed: 16254147
DOI: 10.1182/blood-2004-08-3218 -
Neuro-oncology Jan 2000We conducted a single-arm phase II study to evaluate the efficacy and safety of radiotherapy combined with 6-thioguanine, procarbazine, dibromodulcitol, lomustine, and... (Clinical Trial)
Clinical Trial
We conducted a single-arm phase II study to evaluate the efficacy and safety of radiotherapy combined with 6-thioguanine, procarbazine, dibromodulcitol, lomustine, and vincristine (TPDCV) chemotherapy for treating malignant astrocytoma in children and anaplastic ependymoma in patients of all ages. Between 1984 and 1992, 42 patients who had malignant astrocytomas (glioblastomas multiforme, anaplastic astrocytomas, or mixed anaplastic oligoastrocytomas) were treated with TPDCV chemotherapy and radiation therapy. Of these patients, 40 were younger than 18 years, but 2 were older (22 and 23 years) when treated. Cranial radiation averaged 58 Gy. TPDCV chemotherapy was given for 1 year or until progression. Between 1989 and 1991, 17 patients with malignant ependymoma were treated with TPDCV chemotherapy and craniospinal radiation. Radiation was given at an average dose of 54 Gy to the tumor, 28 Gy to the whole brain, and 31 Gy to the spinal axis. TPDCV chemotherapy was given for 1 year or until tumor progressed. Of the patients with glioblastoma multiforme, 13 of 17 died; the median time to progression was 49 weeks, and median survival was 85 weeks. The four patients surviving at this writing were followed a median 537 weeks (range 364-635 weeks). Of the patients with nonglioblastoma malignant astrocytoma, 14 of 25 died; the median time to progression was 224 weeks. Median survival was not reached in this group. The median follow-up for those surviving was 494 weeks. For the patients with ependymoma, 11 of 17 died with a median time to progression of 141 weeks. The median follow-up for the eight who survive was 469 weeks. Nine patients died with a median survival of 183 weeks. The combination of TPDCV and radiotherapy has activity against childhood anaplastic astrocytoma, glioblastoma multiforme, and anaplastic ependymoma. The results of this study for children with glioblastoma were comparable to results in the literature, while the results for children with anaplastic astrocytoma appeared better than most reports. The combination of TPDCV chemotherapy and radiation therapy for anaplastic ependymomas appears to be active and at least as good as published reports using radiation therapy alone.
Topics: Adolescent; Adult; Antineoplastic Combined Chemotherapy Protocols; Brain Neoplasms; Child; Child, Preschool; Combined Modality Therapy; Female; Glioma; Humans; Lomustine; Male; Mitolactol; Procarbazine; Survival Analysis; Thioguanine; Treatment Outcome; Vincristine
PubMed: 11302250
DOI: 10.1093/neuonc/2.1.22 -
British Journal of Cancer Feb 1995The efficacy and modes of action of dibromodulcitol (DBD) and cisplatin (CDDP) were studied in several model systems. Combination treatments produced a longer survival... (Comparative Study)
Comparative Study
The efficacy and modes of action of dibromodulcitol (DBD) and cisplatin (CDDP) were studied in several model systems. Combination treatments produced a longer survival time in mice bearing P388 solid lymphomas than either of the drugs alone. In the human metastatic melanoma HT-168 xenograft model the combined application of DBD and CDDP was also very effective, inducing a reduction in the number and volume of metastatic nodules. For V79 spheroids, DBD was mainly cytotoxic against the internal, quiescent cells, whereas cisplatin primarily killed cells in the proliferating, external regions of the spheroids. When combined, the drugs appeared to act synergistically throughout the spheroids. Studies on plasmid DNA showed that CDDP primarily generates cross-links, whereas single-strand breaks were dominant after DBD treatment. Upon using an assay for cleavage by restriction nuclease, antagonistic action of DBD and CDDP in combination may occur, nevertheless more strand breaks were always observed in these samples. These results suggest that the efficacy of combined DBD and CDDP is in part a result of 'spatial cooperation' by the drugs (i.e. affecting different cells) and in part the result of DNA damage produced by the combination treatments.
Topics: Animals; Antineoplastic Combined Chemotherapy Protocols; Body Weight; Cisplatin; DNA Damage; DNA, Neoplasm; Drug Screening Assays, Antitumor; Drug Synergism; Leukemia P388; Male; Melanoma; Mice; Mice, Inbred C57BL; Mice, Inbred CBA; Mice, Inbred DBA; Mitolactol; Neoplasm Metastasis; Neoplasm Transplantation; Tumor Cells, Cultured
PubMed: 7841047
DOI: 10.1038/bjc.1995.63 -
Pathology Oncology Research : POR Jun 2010The purpose of this clinicopathological study was to evaluate the effects and efficiency of combined neoadjuvant chemotherapy related to surgical margin. 100... (Clinical Trial)
Clinical Trial
The purpose of this clinicopathological study was to evaluate the effects and efficiency of combined neoadjuvant chemotherapy related to surgical margin. 100 consecutively treated squamous cell cancer patients receiving a combined neoadjuvant therapy were selected (Bleomycin-Vincristin-Methotrexate (BVM) or BVM + Mitolactol or BVM + Cisplatin). After three courses of chemotherapy, the patients were operated on. The largest diameter of the primary tumors was compared before and after chemotherapy. In the surgical specimen, the involvement of surgical margin was assessed. The largest diameter before chemotherapy was: T2 30%; T3 55%; T4A 15%. After chemotherapy, the rest tumor was assessed in the surgical specimen as: no rest 11%; <2 cm 57%; 2-4 cm 28%; 4-6 cm 4%. The no rest and <2 cm (optimal operability) tumor was observed in T2: 94%; in T3: 73%; in the T4A: 0%. Severe side effects (Grade III-IV) were not observed. There was a significant decrease in size (P < 0.0001). Of the 100 surgical specimens, 83% had clear-, 9% close- and 8% involved margins. From T4A, there was a 40% (6 patients) involved margin. Based on the significantly better size and operability of primary T2-3, the mild side effects and the high (83%) percentage of clear surgical margins, that is better than other (without preoperative chemotherapy) results, sought the use of chemotherapy is recommended before surgery. Due to the 40% involved margin, we don't suggest surgery in T4A.
Topics: Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Carcinoma, Squamous Cell; Cisplatin; Female; Humans; Male; Methotrexate; Middle Aged; Mitolactol; Mouth Neoplasms; Neoadjuvant Therapy; Neoplasm Staging; Oral Surgical Procedures; Physicians; Surgery, Oral; Vincristine
PubMed: 19757193
DOI: 10.1007/s12253-009-9208-3