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Oncology (Williston Park, N.Y.) Nov 2008Elderly Hodgkin lymphoma (HL), commonly defined as occuring in patients over 60 to 65 years of age, is an uncommon disease. In population-based studies, the proportion... (Review)
Review
Elderly Hodgkin lymphoma (HL), commonly defined as occuring in patients over 60 to 65 years of age, is an uncommon disease. In population-based studies, the proportion of HL patients over age 60 years has rangedfrom 15% to 30%. However, the proportion of patients over age 60 years in clinical trials has been considerably lower, typically constituting < 5% to 10% of participants. Elderly HL patients commonly present with mixed cellularity histology, B symptoms, advanced stage, and Epstein-Barr virus-positive disease. Progression-free and overall survival rates for elderly HL patients are disproportionately inferior to those of younger patients. Generally, treatment of elderly HL for all disease stages should be given with curative intent, but more effective, tolerable therapeutic regimens are needed. No standard treatment recommendations exist for elderly HL Bleomycin-containing regimens including ABVD (doxorubicin [Adriamycin], bleomycin, vinblastine, dacarbazine) are associated with pulmonary toxicity, and intensive therapy such as BEACOPP (bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine [Oncovin], procarbazine [Matulane], prednisone) is poorly tolerated, whereas less-intensive regimens such as CVP/CEB (chlorambucil [Leukeran], vinblastine, procarbazine, prednisone, cyclophosphamide, etoposide, bleomycin) and ChlVPP (chlorambucil, vinblastine, procarbazine, prednisolone) appear to be less effective than anthracycline-based regimens. Recent data using CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone) in this population merit further investigation. In addition, further evaluation of the prognostic value of early PET in elderly HL is warranted. Continued multicenter collaborations with prospective clinical trials, including formal assessment of comorbidity and functional status, will be critical to the successful study of elderly HL.
Topics: Age Factors; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Disease-Free Survival; Female; Geriatric Assessment; Hodgkin Disease; Humans; Male; Middle Aged; Prognosis; Survival Analysis
PubMed: 19086599
DOI: No ID Found -
CNS Oncology 2015Oligodendroglioma (WHO Grade 2) and anaplastic oligodendroglioma (WHO Grade 3) are glial tumors composed of neoplastic cellular elements that resemble oligodendrocytes.... (Review)
Review
Oligodendroglioma (WHO Grade 2) and anaplastic oligodendroglioma (WHO Grade 3) are glial tumors composed of neoplastic cellular elements that resemble oligodendrocytes. The treatment of recurrent, alkylator refractory oligodendroglial tumors is challenging given the paucity of effective treatment and lack of randomized controlled trials on which to base therapy. Notwithstanding the lack of prospective, randomized data, treatment of oligodendroglial tumors with bevacizumab can be recommended tentatively recognizing that preliminary studies suggest efficacy. Somatic mutations of the isocitrate dehydrogenase enzymes (IDH1 and IDH2) appear to play a critical role in the pathogenesis of most oligodendroglial tumors and agents that target these mutations are a potential therapeutic option. Additionally, reversal of CpG island hypermethylated phenotype status through inhibition of DNA methyltransferase with an inhibitor such as decitabine may provide a target for future studies.
Topics: Angiogenesis Inhibitors; Antineoplastic Combined Chemotherapy Protocols; Bevacizumab; Brain Neoplasms; Humans; Isocitrate Dehydrogenase; Neoplasm Recurrence, Local; Oligodendroglioma; Vascular Endothelial Growth Factor A
PubMed: 26509217
DOI: 10.2217/cns.15.27 -
Environmental and Molecular Mutagenesis Jul 2019Procarbazine hydrochloride (PCH) is a DNA-reactive hematopoietic carcinogen with potent and well-characterized clastogenic activity. However, there is a paucity of in...
Integrated In Vivo Genotoxicity Assessment of Procarbazine Hydrochloride Demonstrates Induction of Pig-a and LacZ Mutations, and Micronuclei, in MutaMouse Hematopoietic Cells.
Procarbazine hydrochloride (PCH) is a DNA-reactive hematopoietic carcinogen with potent and well-characterized clastogenic activity. However, there is a paucity of in vivo mutagenesis data for PCH, and in vitro assays often fail to detect the genotoxic effects of PCH due to the complexity of its metabolic activation. We comprehensively evaluated the in vivo genotoxicity of PCH on hematopoietic cells of male MutaMouse transgenic rodents using a study design that facilitated assessments of micronuclei and Pig-a mutation in circulating erythrocytes, and lacZ mutant frequencies in bone marrow. Mice were orally exposed to PCH (0, 6.25, 12.5, and 25 mg/kg/day) for 28 consecutive days. Blood samples collected 2 days after cessation of treatment exhibited significant dose-related induction of micronuclei in both immature and mature erythrocytes. Bone marrow and blood collected 3 and 70 days after cessation of treatment also showed significantly elevated mutant frequencies in both the lacZ and Pig-a assays even at the lowest dose tested. PCH-induced lacZ and Pig-a (immature and mature erythrocytes) mutant frequencies were highly correlated, with R values ≥0.956, with the exception of lacZ vs. Pig-a mutants in mature erythrocytes at the 70-day time point (R = 0.902). These results show that PCH is genotoxic in vivo and demonstrate that the complex metabolism and resulting genotoxicity of PCH is best evaluated in intact animal models. Our results further support the concept that multiple biomarkers of genotoxicity, especially hematopoietic cell genotoxicity, can be readily combined into one study provided that adequate attention is given to manifestation times. Environ. Mol. Mutagen. 60:505-512, 2019. © 2018 Her Majesty the Queen in Right of Canada.
Topics: Animals; Carcinogens; Cell Nucleus; DNA Damage; Erythrocytes; Hematopoietic Stem Cells; Lac Operon; Male; Mice; Micronucleus Tests; Mutagenesis; Mutagenicity Tests; Mutagens; Mutation; Procarbazine; Reticulocytes
PubMed: 30592561
DOI: 10.1002/em.22271 -
Neurologia Medico-chirurgica 2013World Health Organization grade II gliomas (GIIGs) include diffuse astrocytoma, oligodendroglioma, and oligoastrocytoma. GIIG is a malignant brain tumor for which the... (Comparative Study)
Comparative Study Review
World Health Organization grade II gliomas (GIIGs) include diffuse astrocytoma, oligodendroglioma, and oligoastrocytoma. GIIG is a malignant brain tumor for which the treatment outcome can still be improved. Review of previous clinical trials found the following: (1) GIIG increased in size by 3-5 mm per year when observed or treated with surgery alone; (2) after pathological diagnosis, the survival rate was increased by early aggressive tumor removal at an earlier stage compared to observation alone; (3) although the prognosis after total tumor removal was significantly better than that after partial tumor removal, half of the patients relapsed within 5 years; (4) comparing postoperative early radiotherapy (RT) and non-early RT after relapse, early RT prolonged progression-free survival (PFS) but did not affect overall survival (OS); (5) local RT of 45 to 64.8 Gy did not impact PFS or OS; (6) in patients with residual tumors, RT combined with chemotherapy (procarbazine plus lomustine plus vincristine) prolonged PFS compared with RT alone but did not affect OS; and (7) poor prognostic factors included astrocytoma, non-total tumor removal, age ≥40 years, largest tumor diameter ≥4-6 cm, tumor crossing the midline, and neurological deficit. To improve treatment outcomes, surgery with functional brain mapping or intraoperative magnetic resonance imaging or chemoradiotherapy with temozolomide is important. In this review, current knowledge regarding GIIG is described and treatment strategies are explored.
Topics: Antineoplastic Combined Chemotherapy Protocols; Astrocytoma; Brain Neoplasms; Chemoradiotherapy, Adjuvant; Combined Modality Therapy; Cranial Irradiation; Craniotomy; Early Medical Intervention; Glioma; Humans; Neoplasm Grading; Neoplasm Recurrence, Local; Neoplasm Staging; Neoplasm, Residual; Oligodendroglioma; Randomized Controlled Trials as Topic; Survival Rate
PubMed: 23883553
DOI: 10.2176/nmc.53.429 -
Anticancer Research 2005The safety, tolerance and preliminary efficacy of a chemotherapy regimen consisting of procarbazine (PCB), ranimustine (MCNU) and vincristine (VCR) were assessed for... (Clinical Trial)
Clinical Trial
UNLABELLED
The safety, tolerance and preliminary efficacy of a chemotherapy regimen consisting of procarbazine (PCB), ranimustine (MCNU) and vincristine (VCR) were assessed for patients with newly diagnosed supratentorial anaplastic oligodendroglioma.
MATERIALS AND METHODS
Between October 1999 and September 2003, 5 patients were enrolled. The initial regimens were prescribed as adjuvant therapy in conjunction with radiotherapy following standard surgical treatment. All patients received a chemotherapy comprising ranimustine (100 mg/m2) intravenously on Day 1, procarbazine (60 mg/m2) on Days 8 to 21, and vincristine (1.4 mg/m2, maximum total 2 mg) on Days 8 and 29. The cycles were repeated every 8 weeks until tumor progression was evident, or for a total of 6 cycles over a 1-year period. The primary end-points were safety and tolerability, while the secondary end-point was overall survival.
RESULTS
Five consecutive eligible patients were treated. Of the 4 evaluable patients, 3 partially responded to the treatment (PR), while 1 had a complete response (CR): all patients are still alive. However, 3 of the 5 patients showed relapse, with a time to tumor progression (TTP) of 50, 143 and 241 weeks, respectively. Two of these patients received combined treatment with carboplatin, etoposide and recombinant human mutant tumor necrosis factor-alpha at the first relapse. This regimen appeared to be safe and neither neurological toxicity, severe or life-threatening hematological toxicity, nor fatal toxicity (WHO Grade 4) were experienced.
CONCLUSION
These results suggest that a chemotherapy regimen consisting of PCB, MCNU and VCR in this patient population seems to be safe and tolerable, and the response rate was high. Thus, wide resection with a risk of major neurological morbidity due to nearby functionally critical areas can be avoided. However, since the relapse rate was high, a second-line chemotherapy should be developed for anaplastic oligodendroglioma to improve the long-term control of the disease.
Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Brain Neoplasms; Combined Modality Therapy; Female; Humans; Male; Middle Aged; Nitrosourea Compounds; Oligodendroglioma; Procarbazine; Treatment Outcome; Vincristine
PubMed: 16302731
DOI: No ID Found -
The Oncologist May 2021IDH-mutant anaplastic astrocytomas (AAs) are chemosensitive tumors for which the best choice of adjuvant chemotherapy between procarbazine, lomustine, and vincristine...
Radiotherapy Plus Procarbazine, Lomustine, and Vincristine Versus Radiotherapy Plus Temozolomide for IDH-Mutant Anaplastic Astrocytoma: A Retrospective Multicenter Analysis of the French POLA Cohort.
BACKGROUND
IDH-mutant anaplastic astrocytomas (AAs) are chemosensitive tumors for which the best choice of adjuvant chemotherapy between procarbazine, lomustine, and vincristine (PCV) or temozolomide (TMZ) after radiotherapy (RT) remains unclear.
METHODS
In a large cohort of patients with histologically proven 2016 World Health Organization classification AA with IDH1/2 mutations included in the French national POLA cohort (n = 355), the primary objective was to compare progression-free survival (PFS) between the two treatment regimens (n = 311). Secondary endpoints were overall survival (OS), progression type, pseudoprogression rate, and toxicity.
RESULTS
The 4-year PFS in the RT + PCV arm was 70.8% versus 53.5% in the RT + TMZ arm, with a hazard ratio (HR) of 0.58 (95% confidence interval [CI], 0.38-0.87; p = .0074) in univariable analysis and 0.63 (95% CI, 0.41-0.97; p = .0348) in multivariable analysis. The 4-year OS in the RT + PCV arm was 84.3% versus 76.6% in the RT + TMZ arm, with an HR of 0.57 (95% CI, 0.30-1.05; p = .0675) in univariable analysis. Toxicity was significantly higher in the RT + PCV arm with more grade ≥3 toxicity (46.7% vs. 8.6%, p < .0001).
CONCLUSION
RT + PCV significantly improved PFS compared with RT + TMZ for IDH-mutant AA. However, RT + TMZ was better tolerated.
IMPLICATIONS FOR PRACTICE
In the absence of fully conducted randomized trials comparing procarbazine, lomustine, and vincristine (PCV) with temozolomide (TMZ) in adjuvant treatment after radiotherapy (RT) for the management of IDH-mutant anaplastic astrocytoma (AA) and a similar level of evidence, these two chemotherapies are both equally recommended in international guidelines. This study in a national cohort of IDH-mutant AA defined according the 2016 World Health Organization (WHO) classification shows for the first time that the RT + PCV regimen significantly improves progression-free survival in comparison with the RT + TMZ regimen. Even if at the time of analysis the difference in overall survival was not significant, this result provides new evidence for the debate about the chemotherapy regimen to prescribe in adjuvant treatment to RT for WHO 2016 IDH-mutant AA.
Topics: Antineoplastic Combined Chemotherapy Protocols; Astrocytoma; Brain Neoplasms; Humans; Lomustine; Procarbazine; Retrospective Studies; Temozolomide; Vincristine
PubMed: 33524191
DOI: 10.1002/onco.13701 -
Anticancer Research 2006To evaluate the feasibility, efficacy and toxicity of hyperfractionated radiotherapy and multi-agent chemotherapy, including procarbazine, nimustine (ACNU) and... (Clinical Trial)
Clinical Trial
AIM
To evaluate the feasibility, efficacy and toxicity of hyperfractionated radiotherapy and multi-agent chemotherapy, including procarbazine, nimustine (ACNU) and vincristine, in adults with high-grade gliomas.
MATERIALS AND METHODS
Radiotherapy was administered using two fractions per day of 1.2 Gy to a total dose of 72 Gy. The chemotherapy consisted of procarbazine (90 mg/m2 orally, days 1 to 14), ACNU (80 mg/m2 intravenously, day 1) and vincristine (0.5 mg/m2 intravenously, days 1 and 8) and was administered during and after radiotherapy, up to a maximum of four courses.
RESULTS
From September 1997 to August 1999, a total of ten patients (five with glioblastoma and five with grade 3 gliomas) were enrolled. All ten patients were able to complete a total dose of 72 Gy hyperfractionated radiotherapy with one course of concurrent chemotherapy. Of eight assessable patients, three (38%) had an objective response, comprising two CR and one PR. The median time to progression was 10.7 months and the median survival time of all patients was 15.0 months. Although grade 4 leukopenia and grade 4 thrombocytopenia occurred in 10% and 10% of all patients, respectively, these were transient and no patients developed neutropenic fever or intracranial hemorrhage. No serious non-hematological or late toxicities occurred.
CONCLUSION
Hyperfractionated radiotherapy and multi-agent chemotherapy using procarbazine, ACNU and vincristine is safe and well tolerated for high-grade gliomas.
Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Astrocytoma; Combined Modality Therapy; Dose Fractionation, Radiation; Female; Glioma; Humans; Male; Middle Aged; Nimustine; Oligodendroglioma; Procarbazine; Prospective Studies; Supratentorial Neoplasms; Vincristine
PubMed: 16821632
DOI: No ID Found -
BMC Cancer Feb 2021Following optimal local therapy, adjuvant Procarbazine, Lomustine and Vincristine (PCV) improves overall survival (OS) in low-grade glioma (LGG). However, 1 year of PCV...
BACKGROUND
Following optimal local therapy, adjuvant Procarbazine, Lomustine and Vincristine (PCV) improves overall survival (OS) in low-grade glioma (LGG). However, 1 year of PCV is associated with significant toxicities. In the pivotal RTOG 9802 randomised control trial, approximately half of the patients discontinued treatment after 6 months. As patients on clinical trials may be fitter, we aimed to further explore the tolerability of PCV chemotherapy in routine clinical practice.
METHODS
We conducted a retrospective study between 2014 and 2018 at a National Neuro-Oncology centre. Patients who had received PCV during this time period were included. The primary objective was to assess tolerability of treatment. Secondary objectives included evaluation of treatment delays, dose modifications and toxicities.
RESULTS
Overall, 41 patients were included, 24 (58%) were male and 21 (51%) aged ≥40 years. 38 (93%) underwent surgical resection and all patients received adjuvant radiotherapy prior to chemotherapy. The median number of cycles completed was 3,2,4 for procarbazine, lomustine and vincristine respectively. Only 4 (10%) completed all 6 cycles of PCV without dose modifications. There was a universal decline in dose intensity as cycles of chemotherapy progressed. Dose intensity for cycle 1 versus cycle 6 respectively: procarbazine (98% versus 46%), lomustine (94% versus 48%) and vincristine (93% versus 50%). Haematological toxicities were common. Six (14%) patients experienced Grade III-IV thrombocytopaenia and 13 (31%) experienced Grade III-IV neutropaenia.
CONCLUSION
Toxicities are frequently observed with the PCV regimen in clinical practice. It might be preferable to adjust doses from the start of chemotherapy to improve tolerability or consider alternative chemotherapy, particularly in older patients with LGG.
Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Brain Neoplasms; Drug-Related Side Effects and Adverse Reactions; Female; Follow-Up Studies; Glioma; Humans; Incidence; Ireland; Lomustine; Male; Neoplasm Grading; Procarbazine; Retrospective Studies; Time Factors; Vincristine
PubMed: 33557783
DOI: 10.1186/s12885-021-07809-5 -
Journal of Clinical Oncology : Official... Sep 2013Treatment-related stomach cancer is an important cause of morbidity and mortality among the growing number of Hodgkin lymphoma (HL) survivors, but risks associated with...
PURPOSE
Treatment-related stomach cancer is an important cause of morbidity and mortality among the growing number of Hodgkin lymphoma (HL) survivors, but risks associated with specific HL treatments are unclear.
PATIENTS AND METHODS
We conducted an international case-control study of stomach cancer nested in a cohort of 19,882 HL survivors diagnosed from 1953 to 2003, including 89 cases and 190 matched controls. For each patient, we quantified cumulative doses of specific alkylating agents (AAs) and reconstructed radiation dose to the stomach tumor location.
RESULTS
Stomach cancer risk increased with increasing radiation dose to the stomach (Ptrend < .001) and with increasing number of AA-containing chemotherapy cycles (Ptrend = .02). Patients who received both radiation to the stomach ≥ 25 Gy and high-dose procarbazine (≥ 5,600 mg/m(2)) had strikingly elevated stomach cancer risk (25 cases, two controls; odds ratio [OR], 77.5; 95% CI, 14.7 to 1452) compared with those who received radiation < 25 Gy and procarbazine < 5,600 mg/m(2) (Pinteraction < .001). Risk was also elevated (OR, 2.8; 95% CI, 1.3 to 6.4) among patients who received radiation to the stomach ≥ 25 Gy but procarbazine < 5,600 mg/m(2); however, no procarbazine-related risk was evident with radiation < 25 Gy. Treatment with dacarbazine also increased stomach cancer risk (12 cases, nine controls; OR, 8.8; 95% CI, 2.1 to 46.6), after adjustment for radiation and procarbazine doses.
CONCLUSION
Patients with HL who received subdiaphragmatic radiotherapy had dose-dependent increased risk of stomach cancer, with marked risks for patients who also received chemotherapy containing high-dose procarbazine. For current patients, risks and benefits of exposure to both procarbazine and subdiaphragmatic radiotherapy should be weighed carefully. For patients treated previously, GI symptoms should be evaluated promptly.
Topics: Adolescent; Adult; Aged; Aged, 80 and over; Case-Control Studies; Cohort Studies; Female; Hodgkin Disease; Humans; Male; Middle Aged; Neoplasms, Second Primary; Risk Factors; Stomach Neoplasms; United States; Young Adult
PubMed: 23980092
DOI: 10.1200/JCO.2013.50.6832 -
Annals of Oncology : Official Journal... Jan 1991Initial results from studies with third-generation combination chemotherapy regimens for the treatment of aggressive non-Hodgkin's lymphomas (NHL) demonstrated complete... (Clinical Trial)
Clinical Trial Comparative Study Randomized Controlled Trial Review
Initial results from studies with third-generation combination chemotherapy regimens for the treatment of aggressive non-Hodgkin's lymphomas (NHL) demonstrated complete remission (CR) rates higher than those reported with first-generation regimens. Long-term follow-up of these studies is required to know if the increased number of CRs translates into an increased number of long-term disease-free survivors. In this report, results obtained with one of the third-generation regimens, ProMACE (prednisone/methotrexate/doxorubicin/cyclophosphamide/etoposide)-Cyta BOM (cytarabine/bleomycin/vincristine/methotrexate) are described. From 1981 to 1988, 193 patients with stage II, III, or IV aggressive NHL treated at the National Cancer Institute were randomly assigned to receive either ProMACE (day 1)-CytaBOM (day 8) or ProMACE (day 1)-MOPP (mechlorethamine/vincristine/procarbazine/prednisone) (day 8). With a median follow-up of 5 years, the CR rate was 86% for ProMACE-CytaBOM v 74% for ProMACE-MOPP (P = 0.048). A plateau in the disease-free survival curve is seen at 69% for ProMACE-CytaBOM v 54% for ProMACE-MOPP (P = 0.082). A plateau is also seen in the overall survival curves at 69% for ProMACE-CytaBOM v 53% for ProMACE-MOPP (P = 0.046). The Southwest Oncology Group also conducted a phase II study of ProMACE-CytaBOM in 78 patients with stages II to IV intermediate- or high-grade NHL to determine the CR rate and long-term disease-free survival of this regimen in a national cooperative group setting. The CR rate was 65%. With a median follow-up of 38 months, disease-free survival is 50% at 3 years and overall survival is 57% at the same time point.(ABSTRACT TRUNCATED AT 250 WORDS)
Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Cyclophosphamide; Cytarabine; Doxorubicin; Drug Evaluation; Etoposide; Follow-Up Studies; Humans; Lymphoma, Non-Hodgkin; Mechlorethamine; Methotrexate; Middle Aged; Prednisone; Procarbazine; Remission Induction; Survival Rate; Vincristine
PubMed: 1710487
DOI: 10.1093/annonc/2.suppl_1.33