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The New England Journal of Medicine Jun 2003The use of involved-field radiotherapy after chemotherapy for advanced Hodgkin's lymphoma is controversial. (Clinical Trial)
Clinical Trial Comparative Study Randomized Controlled Trial
BACKGROUND
The use of involved-field radiotherapy after chemotherapy for advanced Hodgkin's lymphoma is controversial.
METHODS
We randomly assigned patients with previously untreated stage III or IV Hodgkin's lymphoma who were in complete remission after hybrid chemotherapy with mechlorethamine, vincristine, procarbazine, prednisone, doxorubicin, bleomycin, and vinblastine (MOPP-ABV) to receive either no further treatment or involved-field radiotherapy. Radiotherapy consisted of 24 Gy to all initially involved nodal areas and 16 to 24 Gy to all initially involved extranodal sites. Patients in partial remission were treated with 30 Gy to nodal areas and 18 to 24 Gy to extranodal sites.
RESULTS
Of 739 patients, 421 had a complete remission; 161 of these patients were assigned to no further treatment, and 172 to involved-field radiotherapy. The median follow-up was 79 months. The five-year event-free survival rate was 84 percent in the group that did not receive radiotherapy and 79 percent in the group that received involved-field radiotherapy (P=0.35). The five-year overall survival rates were 91 and 85 percent, respectively (P=0.07). Among the 250 patients in partial remission after chemotherapy, the five-year event-free and overall survival rates were 79 and 87 percent, respectively.
CONCLUSIONS
Involved-field radiotherapy did not improve the outcome in patients with advanced-stage Hodgkin's lymphoma who had a complete remission after MOPP-ABV chemotherapy. Radiotherapy may benefit patients with a partial response after chemotherapy.
Topics: Adolescent; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Combined Modality Therapy; Doxorubicin; Female; Hodgkin Disease; Humans; Male; Mechlorethamine; Middle Aged; Neoplasm Staging; Neoplasms, Second Primary; Prednisone; Procarbazine; Remission Induction; Survival Analysis; Vinblastine; Vincristine
PubMed: 12802025
DOI: 10.1056/NEJMoa022628 -
Therapeutics and Clinical Risk... Jun 2007Procarbazine HCl is a 'nonclassical' oral alkylating anticancer agent that was first synthesized in the late 1950s. It has been used in the treatment of many cancers,...
Procarbazine HCl is a 'nonclassical' oral alkylating anticancer agent that was first synthesized in the late 1950s. It has been used in the treatment of many cancers, but its main use is in the treatment of Hodgkin's lymphoma and brain tumors and, to a lesser extent, Non-Hodgkin's lymphoma and primary central nervous system lymphoma. Procarbazine is a prodrug that undergoes metabolic transformation into active intermediates that are thought to inhibit DNA, RNA, and protein synthesis. Early use of procarbazine in combination with mechlorethamine, vincristine, and prednisone (MOPP) was effective in the treatment of advanced Hodgkin's lymphoma, but late toxic effects such as secondary cancer and infertility led to its replacement by other regimens. However, its recent reintroduction in the dose-intensified BEACOPP (bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone) regimen has yielded very promising findings. Procarbazine alone, or more commonly combined in the PCV (procarbazine, lomustine [CCNU], and vincristine) regimen, is also effective in treating gliomas comprising astrocytomas, glioblastomas, and oligodendrogliomas. The most common side effects of procarbazine are gastrointestinal disturbances, myelosuppression, and central nervous system effects. In conclusion, the use of procarbazine in combination with other drugs means that it remains a major anticancer drug in the management of Hodgkin's lymphoma and gliomas.
PubMed: 18360630
DOI: 10.2147/tcrm.2007.3.2.213 -
Neuro-oncology Apr 2016Primary intraocular lymphoma is a rare variant of primary CNS lymphoma for which the optimum treatment strategy remains unknown. (Clinical Trial)
Clinical Trial
BACKGROUND
Primary intraocular lymphoma is a rare variant of primary CNS lymphoma for which the optimum treatment strategy remains unknown.
METHODS
We performed a retrospective single-center study including patients who underwent uniform management from October 2007 in which patients were offered sequential rituximab, methotrexate, procarbazine, and vincristine (R-MPV) followed by binocular radiotherapy and consolidative high-dose cytarabine.
RESULTS
Eleven patients with median age 66 years (range, 48-72) were included. All patients received binocular radiotherapy to a median dose of 36 Gy (range, 30.6-39.6) in 20 fractions. Grade 3+ anemia, thrombocytopenia, and neutropenia occurred in 1 (9%), 2 (18%), and 3 (27%) patients, respectively; raised creatinine and peripheral sensory neuropathy occurred in 4 (36%) and 3 (27%) patients, respectively. Grade 3+ ocular toxicities included cataract formation and keratitis in 6 (54%) and 3 (27%) patients, respectively. Ten patients (91%) achieved complete response and 1 (9%) partial response. After median follow-up of 4.2 years (range, 1.8-7.6), the median progression-free survival was 3.8 years and the estimated 4-year overall survival was 75.8% (95% CI: 30.5%-93.7%). The initial site of disease progression was the CNS in 4 of 7 patients (57%) and within the eye in 3 of 7 (43%). Five patients achieved responses to salvage therapies.
CONCLUSIONS
Combined modality treatment with R-MPV, binocular radiation, and high-dose cytarabine is effective with moderate toxicity. Both local and CNS relapses occur; however, the achievement of second and subsequent remissions is possible.
Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Brain Neoplasms; Combined Modality Therapy; Cranial Irradiation; Cytarabine; Female; Follow-Up Studies; Humans; Immunotherapy; Intraocular Lymphoma; Male; Methotrexate; Middle Aged; Neoplasm Recurrence, Local; Neoplasm Staging; Procarbazine; Prognosis; Remission Induction; Retrospective Studies; Salvage Therapy; Survival Rate; Vincristine
PubMed: 26487691
DOI: 10.1093/neuonc/nov253 -
Journal of Cancer Research and Clinical... Feb 2018Although G-CSF is widely used to prevent or ameliorate leukopenia during cytotoxic chemotherapies, its optimal use is still under debate and depends on many therapy...
PURPOSE
Although G-CSF is widely used to prevent or ameliorate leukopenia during cytotoxic chemotherapies, its optimal use is still under debate and depends on many therapy parameters such as dosing and timing of cytotoxic drugs and G-CSF, G-CSF pharmaceuticals used and individual risk factors of patients.
METHODS
We integrate available biological knowledge and clinical data regarding cell kinetics of bone marrow granulopoiesis, the cytotoxic effects of chemotherapy and pharmacokinetics and pharmacodynamics of G-CSF applications (filgrastim or pegfilgrastim) into a comprehensive model. The model explains leukocyte time courses of more than 70 therapy scenarios comprising 10 different cytotoxic drugs. It is applied to develop optimized G-CSF schedules for a variety of clinical scenarios.
RESULTS
Clinical trial results showed validity of model predictions regarding alternative G-CSF schedules. We propose modifications of G-CSF treatment for the chemotherapies 'BEACOPP escalated' (Hodgkin's disease), 'ETC' (breast cancer), and risk-adapted schedules for 'CHOP-14' (aggressive non-Hodgkin's lymphoma in elderly patients).
CONCLUSIONS
We conclude that we established a model of human granulopoiesis under chemotherapy which allows predictions of yet untested G-CSF schedules, comparisons between them, and optimization of filgrastim and pegfilgrastim treatment. As a general rule of thumb, G-CSF treatment should not be started too early and patients could profit from filgrastim treatment continued until the end of the chemotherapy cycle.
Topics: Age Factors; Aged; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Cyclophosphamide; Doxorubicin; Drug Administration Schedule; Etoposide; Filgrastim; Granulocyte Colony-Stimulating Factor; Granulocytes; Hematopoiesis; Humans; Leukopenia; Models, Biological; Neoplasms; Polyethylene Glycols; Prednisone; Procarbazine; Randomized Controlled Trials as Topic; Reproducibility of Results; Vincristine
PubMed: 29103159
DOI: 10.1007/s00432-017-2540-1 -
Blood Dec 1998The BEACOPP (bleomycin, etoposide, adriamycin, cyclophosphamide, vincristine, procarbazine, and prednisone) regimen, a rearranged and accelerated version of the standard... (Clinical Trial)
Clinical Trial
Moderate dose escalation for advanced stage Hodgkin's disease using the bleomycin, etoposide, adriamycin, cyclophosphamide, vincristine, procarbazine, and prednisone scheme and adjuvant radiotherapy: a study of the German Hodgkin's Lymphoma Study Group.
The BEACOPP (bleomycin, etoposide, adriamycin, cyclophosphamide, vincristine, procarbazine, and prednisone) regimen, a rearranged and accelerated version of the standard COPP/adriamycin, bleomycin, vinblastine, and dacarbazine (ABVD) chemotherapy, has been shown to be effective and safe in a previous pilot study for advanced stage Hodgkin's disease (HD). The present study aimed to determine a maximum practicable dose of three drugs, ie, etoposide, adriamycin, and cyclophosphamide, for which acute toxicities were acceptable and to assess the feasibility of the escalated scheme. Sixty untreated patients with advanced stage HD were enrolled in this study. Radiotherapy was given in 44 patients (73%) after chemotherapy to initial bulk lesions and residual disease. Granulocyte-colony stimulating factor (G-CSF) was given from day 8 to prevent prolonged neutrocytopenia and severe infections. The intended doses of adriamycin, etoposide, and cyclophosphamide in the BEACOPP schedule could be substantially escalated: adriamycin from 25 to 35, cyclophosphamide from 650 to 1,200, and etoposide from 100 to 200 mg/m2. The major toxicities were leukocytopenia and thrombocytopenia with considerable heterogeneity between individual patients. Of 60 patients, 56 (93%) achieved a complete remission (CR). At a median observation of 32 months, the rates of survival and freedom from treatment failure (FFTF) were estimated to be 91% (95% confidence interval 83% to 99%) and 90% (82% to 98%). These results show that a moderate dose escalation of adriamycin, cyclophosphamide, and etoposide of the baseline BEACOPP regimen is feasible. The escalated BEACOPP regimen shows very encouraging results in advanced stage HD and is now being compared in a randomized phase III study with BEACOPP at baseline dose level.
Topics: Adolescent; Adult; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Cyclophosphamide; Dose-Response Relationship, Drug; Doxorubicin; Drug Administration Schedule; Etoposide; Female; Filgrastim; Granulocyte Colony-Stimulating Factor; Hodgkin Disease; Humans; Leukemia; Male; Middle Aged; Neoplasms, Second Primary; Prednisone; Procarbazine; Radiotherapy, Adjuvant; Recombinant Proteins; Remission Induction; Survival Rate; Treatment Outcome; Vincristine
PubMed: 9845521
DOI: No ID Found -
Case Reports in Hematology 2022Central nervous system (CNS) involvement in multiple myeloma (MM) (MM-CNS) in the form of leptomeningeal myelomatosis or brain parenchyma plasmacytoma is rare, causing...
Central nervous system (CNS) involvement in multiple myeloma (MM) (MM-CNS) in the form of leptomeningeal myelomatosis or brain parenchyma plasmacytoma is rare, causing challenges in clinical diagnosis and treatment. We would like to report a case of leptomeningeal myelomatosis and illustrated the challeges. A 61-year-old man was diagnosed with MM with left paravertebral plasmacytoma, R-ISS II with high suspicion of double-hit MM, either biallelic aberrancy of TP53 or del(17p) and IGH aberrancy depending on the definition chosen, treated with lenalidomide-bortezomib-dexamethasone and local radiotherapy, later developed systemic relapse and progression to MM-CNS in the form of leptomeningeal myelomatosis. A modified CNS-based treatment not reported before, consisting of daratumumab, pomalidomide, vincristine, procarbazine, and dexamethasone, brought a rapid clinical improvement and warrants a further study. Incorporation of intrathecal thiotepa into the regimen would likely increase the efficacy.
PubMed: 36092151
DOI: 10.1155/2022/4081971 -
Blood Nov 1976The chromosomes of bone marrow cells from ten patients with polycythemia vera (PV) were identified by Q-, G-, and C-banding techniques. Four of the patients had received...
The chromosomes of bone marrow cells from ten patients with polycythemia vera (PV) were identified by Q-, G-, and C-banding techniques. Four of the patients had received no treatment with cytotoxic drugs, while three had received 32P only and the other three, in addition, had received busulfan or busulfan and procarbazine. One 73-yr-old male patient treated with venesection only for 4 yr lacked the Y chromosome and had a deletion of the long arm of chromosome 20 (20q-) in all cells investigated. One of the other three patients who had received no drugs had a chromosome abnormality, but only in 1 of 19 identifiable metaphases. However, the abnormality was the same (+9) as the most common one in treated patients. In the group of treated patients, an extra chromosome 9 (+9) was found in three patients, an extra chromosome 8 (+8) in one, and a deletion of the long arm of one chromosome 20 (20q-) in one patient. Multiple aberrations in addition to the extra chromosome 9 were found in one patient in whom the disease had transformed into acute myeloblastic leukemia. The finding of identical chromosomal aberrations (20q- and +9, respectively) in two patients who had received no drugs and in four patients who had received 32P and busulfan or procarbazine favors the view that these aberrations are specifically associated with the disease and not induced by the drugs. With the exception of the patient with acute myeloblastic leukemia, all other patients are alive 1-11 mo after chromosome analyses and 1-229 mo after diagnosis.
Topics: Aged; Chromosome Aberrations; Chromosome Disorders; Chromosomes, Human, 19-20; Chromosomes, Human, 6-12 and X; Female; Humans; Male; Middle Aged; Polycythemia Vera; Sex Chromosome Aberrations; Sex Chromosomes
PubMed: 974265
DOI: No ID Found -
Asian Pacific Journal of Cancer... 2016With advances in diagnostics and treatment approaches, patients with Hodgkin's lymphoma (HL) in developed countries can nowadays expect to have excellent outcomes....
BACKGROUND
With advances in diagnostics and treatment approaches, patients with Hodgkin's lymphoma (HL) in developed countries can nowadays expect to have excellent outcomes. However, information about the characteristics and outcomes in the developing world is very scarce, and this is important given the fact that there are several reports about differences of disease characteristics depending on geographic location and the development level of the country.
MATERIALS AND METHODS
In this retrospective study we assessed the features of 36 adult (≥18 years old) patients with HL and their diagnosis and treatment and outcomes in the Clinic of Chemotherapy of Muratsan University Hospital of Yerevan State Medical University, Armenia, between 2008- 2014.
RESULTS
All patients had classic HL and among them 19 (53%) had nodular sclerosis subtype, 8 (22%) mixed cellularity and 9 (25%) lymphocyte-rich. 16 (44.5%) patients were at stage II, 13 (36%) stage III and 7 (19.5%) stage IV. Median follow-up time was 24.5 months (range 1-71 months) and during the whole follow- up period only two relapses (early) were documented and there were no deaths. Twenty-three (64%) patients received a BEACOPP (bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone) regimen, and 13 (36%) ABVD (doxorubicin, bleomycin, vinblastine and dacarbazine) regimen. A total of 25 (69.5%) patients received radiation in addition to chemotherapy.
CONCLUSIONS
Although the number of patients involved in the study is small and the median follow-up time was just two years, this retrospective study shows that treatment of HL can be successfully organized in a resource-limited setting.
Topics: Adolescent; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Armenia; Bleomycin; Combined Modality Therapy; Cyclophosphamide; Dacarbazine; Developed Countries; Doxorubicin; Etoposide; Female; Hodgkin Disease; Hospitals; Humans; Lymphoma; Male; Middle Aged; Neoplasm Recurrence, Local; Prednisone; Procarbazine; Retrospective Studies; Vinblastine; Vincristine; Young Adult
PubMed: 26838192
DOI: 10.7314/apjcp.2016.17.1.101 -
Blood Feb 2015In this issue of Blood, Omuro et al report the results of a phase 2 study for patients with newly diagnosed primary central nervous system lymphoma (PCNSL) using...
In this issue of Blood, Omuro et al report the results of a phase 2 study for patients with newly diagnosed primary central nervous system lymphoma (PCNSL) using induction immunochemotherapy (rituximab, high-dose methotrexate [MTX], vincristine, procarbazine) followed by a novel consolidation high-dose chemotherapy (thiotepa, busulfan, cyclophosphamide) and autologous stem cell transplantation (HDC-ASCT).
Topics: Antineoplastic Combined Chemotherapy Protocols; Central Nervous System Neoplasms; Female; Hematopoietic Stem Cell Transplantation; Humans; Lymphoma, Non-Hodgkin; Male
PubMed: 25721041
DOI: 10.1182/blood-2015-01-622498 -
Blood May 1996In the Working Formulation (WF), non-Hodgkin's lymphomas (NHL) are grouped according to their clinical behavior. These disorders are listed as entities defined by... (Clinical Trial)
Clinical Trial Comparative Study Randomized Controlled Trial Review
Clinical analysis of 670 cases in two trials of the European Organization for the Research and Treatment of Cancer Lymphoma Cooperative Group subtyped according to the Revised European-American Classification of Lymphoid Neoplasms: a comparison with the Working Formulation.
In the Working Formulation (WF), non-Hodgkin's lymphomas (NHL) are grouped according to their clinical behavior. These disorders are listed as entities defined by morphology, phenotype, and cytogenetics in the proposed Revised European-American Classification of Lymphoid Neoplasms (REAL), the clinical relevance of which is still debated. We analyzed 670 NHL cases included in two randomized clinical trials (EORTC 20855 WF-intermediate/high-grade and 20856 WF-low-grade malignancy) with histologic material available for review. Based on hematoxylin-eosin-stained sections, 77% of cases could be subtyped. Immunophenotyping was considered to be mandatory only in diagnosing T-cell lymphoma and anaplastic large-cell lymphoma. Of 522 cases subtyped, 11% were mantle cell lymphoma (MCL), 5% were marginal zone B-cell lymphoma (MZBCL), 46% were follicle center lymphoma, and 32% were diffuse large B-cell lymphoma. Statistical analysis and comparisons between classifications were made only within each trial and treatment group. MCL and MZBCL were characterized by a shorter median survival (3.4 and 4.1 years, respectively) in comparison with low- and intermediate-grade WF groups (> 9.3 and 5.8 years, respectively). In terms of progression-free survival, MCL showed a behavior similar to the low-grade group, with frequent relapses. Follicle center cell lymphomas behaved as low-grade lymphomas as defined by the WF and diffuse large B-cell lymphomas as the WF-intermediate grade group. Because several NHL entities have a clinical behavior of their own, their recognition by the REAL classification offers clinicians additional information that is not obtained when the WF is used.
Topics: Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Bone Marrow; Combined Modality Therapy; Cyclophosphamide; Disease-Free Survival; Doxorubicin; Etoposide; Humans; Immunologic Factors; Immunophenotyping; Interferon alpha-2; Interferon-alpha; Life Tables; Lymphoma, Non-Hodgkin; Mechlorethamine; Methotrexate; Prednisone; Procarbazine; Prognosis; Recombinant Proteins; Survival Analysis; Survival Rate; Vincristine
PubMed: 8639796
DOI: No ID Found