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Future Medicinal Chemistry Jan 2020Steroidal prodrugs of nitrogen mustards such as estramustine and prednimustine have proven effective anticancer agents in clinical use since the 1970s. In this work, we...
Steroidal prodrugs of nitrogen mustards such as estramustine and prednimustine have proven effective anticancer agents in clinical use since the 1970s. In this work, we aimed to develop steroidal prodrugs of the novel nitrogen mustard POPAM-NH. POPAM-NH is a melphalan analogue that was coupled with three different steroidal lactams. The new conjugates were preclinically tested for anticancer activity against nine human and one rodent cancer experimental models, and . All the steroidal alkylators showed high antitumor activity, and , in the experimental systems tested. Moreover, these hybrid compounds showed by far superior anticancer activity compared with the alkylating agents, melphalan and POPAM-NH.
Topics: Aniline Mustard; Animals; Antineoplastic Agents; Apoptosis; Cell Cycle; Cell Proliferation; Dose-Response Relationship, Drug; Drug Discovery; Drug Screening Assays, Antitumor; Female; HT29 Cells; Humans; Injections, Intraperitoneal; Lactams; Male; Mice; Mice, SCID; Neoplasms, Experimental; Propionates; Steroids; Structure-Activity Relationship
PubMed: 31729254
DOI: 10.4155/fmc-2019-0255 -
Taiwanese Journal of Obstetrics &... Sep 2019
Topics: Antineoplastic Combined Chemotherapy Protocols; Etoposide; Female; Gestational Trophoblastic Disease; Humans; Mitoxantrone; Prednimustine; Pregnancy
PubMed: 31542101
DOI: 10.1016/j.tjog.2019.07.026 -
Taiwanese Journal of Obstetrics &... Sep 2019
Topics: Antineoplastic Combined Chemotherapy Protocols; Etoposide; Female; Gestational Trophoblastic Disease; Humans; Mitoxantrone; Prednimustine; Pregnancy
PubMed: 31542075
DOI: 10.1016/j.tjog.2019.07.001 -
Journal of Geriatric Oncology Nov 2015The purpose of this prospective observational study is to evaluate the relation of the comprehensive geriatric assessment (CGA) to tolerability and survival of... (Observational Study)
Observational Study
OBJECTIVES
The purpose of this prospective observational study is to evaluate the relation of the comprehensive geriatric assessment (CGA) to tolerability and survival of multi-agent chemotherapy for curative intent in elderly patients with aggressive non-Hodgkin lymphoma (NHL).
MATERIALS AND METHODS
Patients who were 1) age ≥65 years, 2) newly diagnosed aggressive NHL, and 3) treated with multi-agent chemotherapy within 2 weeks from the time of diagnosis were enrolled from January 2011 to June 2014. Baseline clinical, laboratory, and CGA data being composed of Mini Nutritional Assessment-Short Form (MNA-SF), Korean version of Mini Mental Status Exam, Korean-Geriatric Depression Scale, and Groningen Frailty Index (GFI), were collected and analyzed for the relation to the outcome factors.
RESULTS
Seventy patients were included; the median age was 73.5 years, 27 (38.6%) patients were Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 2 or more, and half of the patients were high or high-intermediate risk by age-adjusted international prognostic index (aaIPI). Most patients received CHOP or CHOP-like chemotherapy. Factors affecting discontinuation of chemotherapy within 12 weeks were poor MNA-SF, poor GFI, poor PS, and presence of B symptom. Among those, poor MNA-SF was independent of other variables in multivariate analysis. Poor MNA-SF, bone marrow involvement, and baseline anemia of hemoglobin<10g /dL were found to be independent factors associated with inferior overall survival whereas aaIPI factors were not.
CONCLUSION
MNA-SF predicted tolerability to multi-agents chemotherapy and overall survival in elderly patients with aggressive NHL who were treated with multi-agent chemotherapy.
Topics: Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Cyclophosphamide; Doxorubicin; Etoposide; Female; Frail Elderly; Geriatric Assessment; Glyoxal; Humans; Ifosfamide; Lymphoma, Non-Hodgkin; Male; Multivariate Analysis; Neoplasm Grading; Prednimustine; Prednisone; Prospective Studies; Republic of Korea; Treatment Outcome; Vincristine
PubMed: 26522808
DOI: 10.1016/j.jgo.2015.10.183 -
Annals of Oncology : Official Journal... Mar 2011Using a parametric carcinogenesis model, we disentangle the superimposing effects of primary and relapse therapies of Hodgkin's disease on secondary neoplasias.
Impact of first- and second-line treatment for Hodgkin's lymphoma on the incidence of AML/MDS and NHL--experience of the German Hodgkin's Lymphoma Study Group analyzed by a parametric model of carcinogenesis.
BACKGROUND
Using a parametric carcinogenesis model, we disentangle the superimposing effects of primary and relapse therapies of Hodgkin's disease on secondary neoplasias.
PATIENTS AND METHODS
We analyze eight randomized trials of the German Hodgkin's lymphoma study group [5357 individuals, 67 secondary acute myeloid leukemia (AML)/myelodysplastic syndrome (MDS) and 97 secondary non-Hodgkin's lymphoma (NHL)]. Primary therapies were divided into four groups: radiotherapy alone, moderately dosed COPP/ABVD-like chemotherapies for intermediate and advanced stages and BEACOPP escalated.
RESULTS
For secondary AML/MDS, the hazards after primary therapies are proportional (maximum at 3.4 years), while the hazard after relapse therapy is more peaked (maximum at 1.8 years). Intermediate and advanced stage chemotherapy resulted in a cumulative risk of 1.5%, while the risk after BEACOPP escalated is higher (4.4%, P = 0.004) and comparable with that after relapse therapy (4.5%). For secondary NHL, there are no differences in cumulative risk between the primary therapies (2.9%), while the risk after relapse therapy is increased (6.6%, P = 0.002).
CONCLUSIONS
BEACOPP escalated moderately increases the risk of secondary AML/MDS but not NHL. No differences were found between other chemotherapies of advanced stages and intermediate stages. Secondary AML/MDS occurs faster after relapse treatment than after primary treatment.
Topics: Algorithms; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Cyclophosphamide; Dacarbazine; Doxorubicin; Etoposide; Glyoxal; Hodgkin Disease; Humans; Ifosfamide; Kaplan-Meier Estimate; Leukemia, Myeloid, Acute; Lymphoma, Non-Hodgkin; Myelodysplastic Syndromes; Neoplasms, Second Primary; Prednimustine; Prednisone; Procarbazine; Proportional Hazards Models; Randomized Controlled Trials as Topic; Risk Assessment; Treatment Outcome; Vinblastine; Vincristine
PubMed: 20720088
DOI: 10.1093/annonc/mdq408 -
[Rinsho Ketsueki] the Japanese Journal... Aug 2008
Review
Topics: Antineoplastic Combined Chemotherapy Protocols; Carboplatin; Clinical Trials as Topic; Combined Modality Therapy; Cyclophosphamide; Dexamethasone; Doxorubicin; Etoposide; Glyoxal; Humans; Ifosfamide; Lymphoma, Extranodal NK-T-Cell; Peripheral Blood Stem Cell Transplantation; Prednimustine; Prednisolone; Prognosis; Radiotherapy; Vincristine
PubMed: 18800601
DOI: No ID Found -
The Journal of Infection Jun 2006Hypersensitivity to mosquito bite (HMB) can occur in association with chronic Epstein-Barr virus (EBV) infection and natural killer (NK) cell leukaemia/lymphoma, which...
Hypersensitivity to mosquito bite (HMB) can occur in association with chronic Epstein-Barr virus (EBV) infection and natural killer (NK) cell leukaemia/lymphoma, which was named 'Tokura-Ishihara disease'. This disease is very rare and most previous reports have been documented in Japan. We present a patient who suffered from of pustules on skin, high fever, myalgia and multiple lymph node enlargements after mosquito bite from childhood. Recently, multiple lymph nodes were palpable on his both inguinal area. Peripheral blood smear (PBS) revealed many large granular lymphocytes and the skin lesion showed a dense dermal and subcutaneous infiltrate of lymphocytes. The lymph nodes and perinodal adipose tissue were infiltrated by atypical lymphoid cells in which EBER-positive signals were identified by in situ hybridization using EBV encoded RNA-1 probe. He was diagnosed as having Tokura-Ishihara disease and receives chemotherapy now. Here, we report a case of this disease with a precise pathological description on the lymph node biopsy.
Topics: Adult; Animals; Antineoplastic Combined Chemotherapy Protocols; Biopsy; Culicidae; Epstein-Barr Virus Infections; Etoposide; Glyoxal; Humans; Hypersensitivity; Ifosfamide; Insect Bites and Stings; Killer Cells, Natural; Lymph Nodes; Lymphocytes; Lymphoma; Male; Prednimustine; Skin
PubMed: 16246422
DOI: 10.1016/j.jinf.2005.08.035 -
Journal of Clinical Oncology : Official... Sep 2005To evaluate a salvage therapy (ST-HD-86) for patients with progressive and relapsed Hodgkin's disease after primary treatment in the pediatric DAL/GPOH studies. The...
PURPOSE
To evaluate a salvage therapy (ST-HD-86) for patients with progressive and relapsed Hodgkin's disease after primary treatment in the pediatric DAL/GPOH studies. The essential chemotherapeutic regimens were ifosfamide, etoposide, and prednisone (IEP) and doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD).
METHODS
One hundred seventy-six patients with progression (n = 51) or first relapse (n = 125) were enrolled by 67 centers. The median time from initial diagnosis to progression/relapse was 1.1 year (range, 0.1 to 15.3 years), and the patients' median age was 14.7 years (range, 4.3 to 24.5 years). Salvage chemotherapy consisted of two to three cycles of IEP alternating with one to two cycles of ABVD supplemented in part by one to two cycles of cyclophosphamide, vincristine, procarbazine, and prednisone or lomustine (CCNU), etoposide, and prednimustine. Radiotherapy was given to involved areas using individualized doses. In the 1990s, additional high-dose chemotherapy with autologous stem-cell transplantation (SCT) was introduced for patients with unfavorable prognosis.
RESULTS
Disease-free survival (DFS) and overall survival (OS) after 10 years are 62% and 75%, respectively (SE, 4% each). Of 176 patients, 73 suffered second events. The risk-factor analysis revealed the time to progression/relapse as the strongest prognostic factor (P = .0001). Patients with progression have an inferior outcome (DFS, 41%; OS, 51%), whereas patients with late relapse (> 12 months after end of therapy) do well (DFS, 86%; OS, 90%), although none of them received SCT in second remission.
CONCLUSION
The result can be considered favorable. Whereas the salvage strategy for progressive disease has to be optimized further, it is possible to reduce intensity and avoid SCT in late relapses after Hodgkin's disease in childhood/adolescence.
Topics: Adolescent; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Child; Child, Preschool; Dacarbazine; Disease Progression; Disease-Free Survival; Doxorubicin; Female; Hodgkin Disease; Humans; Infant; Male; Recurrence; Retrospective Studies; Salvage Therapy; Vinblastine
PubMed: 16135485
DOI: 10.1200/JCO.2005.07.930 -
Annals of Hematology Mar 2004Chemotherapy-treated patients with advanced Hodgkin's disease (HD) differ considerably in acute hematotoxicity. Hematotoxicity may be indicative of pharmacological and...
Chemotherapy-treated patients with advanced Hodgkin's disease (HD) differ considerably in acute hematotoxicity. Hematotoxicity may be indicative of pharmacological and metabolic heterogeneity. We hypothesized that low hematotoxicity might correlate with reduced systemic dose and thus reduced disease control. A total of 266 patients with advanced HD treated with cyclophosphamide, vincristine, procarbazine, prednisone, doxorubicin, bleomycin, vinblastine, and dacarbazine (COPP-ABVD) were analyzed (HD6 trial of the German Hodgkin's Lymphoma Study Group). The reported WHO grade of leukocytopenia was averaged over chemotherapy cycles given and weighted with the reciprocal dose intensity of the corresponding cycle. The low and high toxicity groups were defined in retrospect as having had an averaged WHO grade of leukocytopenia =2.1 and >2.1, respectively. The independent impact of low hematological toxicity on freedom from treatment failure (FFTF) was assessed multivariately adjusting for the international prognostic score for advanced HD. The results were validated in two independent cohorts [181 patients treated with COPP-ABVD (HD9-trial) and 250 patients treated with COPP-ABV-ifosfamide, methotrexate, etoposide, and prednisone (IMEP) (HD6 trial)]. The 5-year FFTF rates were 68% for patients with high toxicity vs 47% for patients with low toxicity [multivariate relative risk (RR) 2.0, 95% confidence interval (CI) 1.4-3.0, p=0.0002]. Patients with low toxicity received significantly higher nominal dose ( p=0.02) and dose intensity ( p<0.0001). This finding was confirmed in both validation cohorts (multivariate RR 2.1, 95% CI 1.2-3.8, p=0.01 and RR 1.5, 95% CI 1.01-2.26, p=0.04, respectively). Patients with low hematotoxicity have significantly higher failure rates despite higher doses and dose intensity. Hematotoxicity is an independent prognostic factor for treatment outcome. This observation suggests a strategy of individualized dosing adapted to hematotoxicity.
Topics: Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Bone Marrow; Cohort Studies; Cyclophosphamide; Dacarbazine; Doxorubicin; Etoposide; Female; Glyoxal; Hematologic Diseases; Hodgkin Disease; Humans; Ifosfamide; Male; Prednimustine; Prednisone; Procarbazine; Prognosis; Retrospective Studies; Severity of Illness Index; Treatment Outcome; Vinblastine; Vincristine
PubMed: 15064867
DOI: 10.1007/s00277-003-0727-9 -
Annals of Oncology : Official Journal... Feb 2004The purpose of this study was to compare the efficacy of the hybrid chemotherapeutic regimen COPP/ABV/IMEP... (Clinical Trial)
Clinical Trial Randomized Controlled Trial
Treatment of advanced Hodgkin's disease with COPP/ABV/IMEP versus COPP/ABVD and consolidating radiotherapy: final results of the German Hodgkin's Lymphoma Study Group HD6 trial.
BACKGROUND
The purpose of this study was to compare the efficacy of the hybrid chemotherapeutic regimen COPP/ABV/IMEP (cyclophosphamide-vincristine-procarbazine-prednisone-doxorubicin-bleomycin-vinblastine-ifosfamide-methotrexate-etoposide) (CAI) with that of the standard regimen COPP/ABVD (COPP/ABV, dacarbacine) (CA) in the treatment of advanced-stage Hodgkin's disease (HD).
PATIENTS AND METHODS
Between January 1988 and January 1993, 588 eligible patients with HD in stages IIIB and IV were randomly assigned to a treatment or control group. The treatment group received four cycles of CAI over a complete cycle duration of 43 days. The control group received four cycles of CA over 57 days. Both groups then received consolidating radiotherapy.
RESULTS
Five hundred and eighty-four patients were suitable for arm comparison. Patients in each group were similar in age, sex, histological subtype and clinical risk factors. Complete remission rates, overall survival and freedom from treatment failure at 7 years were similar for the two groups: 77% versus 78%, 73% versus 73% and 54% versus 56% for CAI and CA, respectively. Differences in acute chemotherapy-related toxicity were significant, however. Prognostic factor analysis confirmed the relevance of the International Prognostic Index and revealed that stage IVB, low hemoglobin, low lymphocyte count, high age and male gender were associated with a poor prognosis
CONCLUSION
The rapidly alternating hybrid CAI did not give superior results when compared with the standard regimen CA in advanced-stage HD.
Topics: Adolescent; Adult; Age Factors; Aged; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Combined Modality Therapy; Cyclophosphamide; Dacarbazine; Doxorubicin; Drug Administration Schedule; Etoposide; Female; Glyoxal; Hodgkin Disease; Humans; Ifosfamide; Male; Middle Aged; Prednimustine; Prednisone; Procarbazine; Prognosis; Sex Factors; Treatment Outcome; Vinblastine; Vincristine
PubMed: 14760122
DOI: 10.1093/annonc/mdh046