-
BMC Cancer Feb 2017Second primary malignancies are a major cause of excess morbidity and mortality in cancer survivors. Hodgkin lymphoma survivors who were treated with infradiaphragmatic... (Clinical Trial)
Clinical Trial
BACKGROUND
Second primary malignancies are a major cause of excess morbidity and mortality in cancer survivors. Hodgkin lymphoma survivors who were treated with infradiaphragmatic radiotherapy and/or high-dose procarbazine have an increased risk to develop colorectal cancer. Colonoscopy surveillance plays an important role in colorectal cancer prevention by removal of the precursor lesions (adenomas) and early detection of cancer, resulting in improved survival rates. Therefore, Hodgkin lymphoma survivors treated with infradiaphragmatic radiotherapy and/or high-dose procarbazine could benefit from colonoscopy, or other surveillance modalities, which are expected to reduce colorectal cancer incidence and mortality. Current knowledge on clinicopathological and molecular characteristics of therapy-related colorectal cancer is limited. The pathogenesis of such colorectal cancers might be different from the pathogenesis in the general population and therefore these patients might require a different clinical approach. We designed a study with the primary aim to assess the diagnostic yield of a first surveillance colonoscopy among Hodgkin lymphoma survivors at increased risk of colorectal cancer and to compare these results with different screening modalities in the general population. Secondary aims include assessment of the test characteristics of stool tests and evaluation of burden, acceptance and satisfaction of CRC surveillance through two questionnaires.
METHODS/DESIGN
This prospective multicenter cohort study will include Hodgkin lymphoma survivors who survived ≥8 years after treatment with infradiaphragmatic radiotherapy and/or procarbazine (planned inclusion of 259 participants). Study procedures will consist of a surveillance colonoscopy with removal of precursor lesions (adenomas) and 6-8 normal colonic tissue biopsies, a fecal immunochemical test and a stool DNA test. All neoplastic lesions encountered will be classified using relevant histomorphological, immunohistochemical and molecular analyses in order to obtain more insight into colorectal carcinogenesis in Hodgkin lymphoma survivors. The Miscan-model will be used for cost-effectiveness analyses.
DISCUSSION
Evaluation of the diagnostic performance, patient acceptance and burden of colorectal cancer surveillance is necessary for future implementation of an individualized colorectal cancer surveillance program for Hodgkin lymphoma survivors. In addition, more insight into treatment-induced colorectal carcinogenesis will provide the first step towards prevention and personalized treatment. This information may be extrapolated to other groups of cancer survivors.
TRIAL REGISTRATION
Registered at the Dutch Trial Registry (NTR): NTR4961 .
Topics: Adenoma; Adolescent; Adult; Aged; Antineoplastic Agents; Antineoplastic Protocols; Colonoscopy; Colorectal Neoplasms; Cost-Benefit Analysis; DNA, Neoplasm; Early Detection of Cancer; Feces; Hodgkin Disease; Humans; Immunochemistry; Middle Aged; Neoplasms, Second Primary; Procarbazine; Prospective Studies; Research Design; Survivors; Young Adult
PubMed: 28173773
DOI: 10.1186/s12885-017-3089-8 -
Cancer Jul 2018
Comparative Study
Topics: Adult; Antineoplastic Agents, Alkylating; Antineoplastic Combined Chemotherapy Protocols; Brain Neoplasms; Chemotherapy, Adjuvant; Chromosome Deletion; Chromosomes, Human, Pair 1; Chromosomes, Human, Pair 19; DNA Methylation; DNA Modification Methylases; DNA Repair Enzymes; Disease-Free Survival; Drug Administration Schedule; Glioma; Humans; Lomustine; Neoplasm Grading; Procarbazine; Promoter Regions, Genetic; Quality of Life; Randomized Controlled Trials as Topic; Temozolomide; Tumor Suppressor Proteins; Vincristine
PubMed: 29698549
DOI: 10.1002/cncr.31371 -
Cancer Nov 2004To the authors' knowledge, there is a scarcity of accurate data regarding the feasibility of standard chemotherapy with procarbazine, lomustine, and vincristine (PCV) in...
Efficacy and feasibility of standard procarbazine, lomustine, and vincristine chemotherapy in anaplastic oligodendroglioma and oligoastrocytoma recurrent after radiotherapy. A Phase II study.
BACKGROUND
To the authors' knowledge, there is a scarcity of accurate data regarding the feasibility of standard chemotherapy with procarbazine, lomustine, and vincristine (PCV) in a homogeneous series of patients with primary anaplastic oligodendroglioma (AO) and oligoastrocytoma (AOA) that was recurrent after surgery and standard radiotherapy. The aim of the current study was to evaluate the overall response rate, toxicity, and time to progression (TTP) with the use of standard PCV in this setting.
METHODS
Between November 1994 and September 2000, 37 patients were enrolled in the current study. Of these, 23 had AO (62%) and 14 had AOA (38%). All patients received standard PCV comprised of lomustine (110 mg/m2) on Day 1, procarbazine (60 mg/m2) on Days 8-21, and vincristine (1.4 mg/m2, maximum total 2 mg) on Days 8 and 29. Cycles were repeated every 6 weeks.
RESULTS
There were 11 complete responses (CR; 29.7%) and 11 partial responses (PR; 29.7%) reported and 8 patients had stable disease (SD; 21.6%). The response rate was higher in patients with AO compared with patients with AOA (77.2% vs. 22.7%; P = 0. 02). The median TTP, which was 12.3 months overall, was 30.3 months in patients who achieved a CR, 19.1 months in patients who achieved a PR, and 6.1 months in patients with SD. The median TTP was 18.6 months in AO patients and 6.14 in AOA patients. There were no cases of severe toxicity reported although in 16 patients (43%) who were free of disease progression, PCV was discontinued because of toxicity or inadequate recovery after 2 weeks of delay.
CONCLUSIONS
PCV chemotherapy was reported to achieved a high response rate and TTP but incurred a high risk of persistent toxicity.
Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Astrocytoma; Combined Modality Therapy; Female; Humans; Lomustine; Male; Middle Aged; Oligodendroglioma; Procarbazine; Recurrence; Vincristine
PubMed: 15372474
DOI: 10.1002/cncr.20611 -
Oncology (Williston Park, N.Y.) Apr 2013Abstract: Anaplastic oligodendroglioma (AO) is a rare malignant tumor occurring in adults. Despite early indications of chemosensitivity, no clinical trial had... (Review)
Review
Abstract: Anaplastic oligodendroglioma (AO) is a rare malignant tumor occurring in adults. Despite early indications of chemosensitivity, no clinical trial had demonstrated a benefit of chemotherapy beyond that of radiotherapy alone. Now, however, the Radiation Therapy Oncology Group (RTOG) 9402 and the European Organisation for Research and Treatment of Cancer (EORTC) 26951 studies investigating PCV (procarbazine [Matulane], lomustine [CeeNU], and vincristine) and radiation therapy vs radiation alone both show improved outcomes in patients with the 1 p/19q codeletion who received PCV and radiation therapy. These differences were detected with additional follow-up after publication of the initial results in 2006, when no differences in survival were detected. The two studies have also validated the use of the 1p/19q codeletion as a predictive biomarker in AO. Many will debate the wisdom of adopting PCV therapy as standard of care because of the greater toxicity of PCV compared with temozolomide (Temodar). Nonetheless, although important questions still remain regarding chemotherapy choice, sequence, and dosing, the answers to which will require additional large phase III trials, radiotherapy alone is no longer appropriate therapy for 1p/19q codeleted AOs.
Topics: Brain Neoplasms; Dacarbazine; Humans; Isocitrate Dehydrogenase; Mutation; Oligodendroglioma; Temozolomide
PubMed: 23781695
DOI: No ID Found -
Movement Disorders : Official Journal... Jun 2019Spreading depolarization (SD) is a transient self-propagating wave of neuronal and glial depolarization coupled with large membrane ionic changes and a subsequent...
OBJECTIVE
Spreading depolarization (SD) is a transient self-propagating wave of neuronal and glial depolarization coupled with large membrane ionic changes and a subsequent depression of neuronal activity. Spreading depolarization in the cortex is implicated in migraine, stroke, and epilepsy. Conversely, spreading depolarization in the striatum, a brain structure deeply involved in motor control and in Parkinson's disease (PD) pathophysiology, has been poorly investigated.
METHODS
We characterized the participation of glutamatergic and dopaminergic transmission in the induction of striatal spreading depolarization by using a novel approach combining optical imaging, measurements of endogenous DA levels, and pharmacological and molecular analyses.
RESULTS
We found that striatal spreading depolarization requires the concomitant activation of D1-like DA and N-methyl-d-aspartate receptors, and it is reduced in experimental PD. Chronic l-dopa treatment, inducing dyskinesia in the parkinsonian condition, increases the occurrence and speed of propagation of striatal spreading depolarization, which has a direct impact on one of the signaling pathways downstream from the activation of D1 receptors.
CONCLUSION
Striatal spreading depolarization might contribute to abnormal basal ganglia activity in the dyskinetic condition and represents a possible therapeutic target. © 2019 International Parkinson and Movement Disorder Society.
Topics: Animals; Antineoplastic Combined Chemotherapy Protocols; Antiparkinson Agents; Corpus Striatum; Dopaminergic Neurons; Dyskinesia, Drug-Induced; Levodopa; Neurons; Nitrogen Mustard Compounds; Parkinsonian Disorders; Prednisolone; Procarbazine; Rats; Rats, Wistar; Synaptic Transmission; Vincristine
PubMed: 30759320
DOI: 10.1002/mds.27632 -
Oncology (Williston Park, N.Y.) Jan 2017Interim positron emission tomography (PET)/CT has shown encouraging results when used as a prognostic tool early in the course of treatment of advanced Hodgkin lymphoma,... (Review)
Review
Interim positron emission tomography (PET)/CT has shown encouraging results when used as a prognostic tool early in the course of treatment of advanced Hodgkin lymphoma, allowing for a reduction in treatment for patients with favorable characteristics, while suggesting a benefit from changing therapy for those with a positive scan. For patients with limited disease, a negative scan allows for a decrease in treatment; however, the benefits for those patients whose scans are positive are less certain. Here we critically analyze the role of PET/CT in the early assessment of Hodgkin lymphoma. In Part 2, we will review the role of interim PET/CT in diffuse large B-cell lymphoma (DLBCL), and also explore the question of whether new approaches to quantitative assessment improve the prognostic value of interim PET scans in both Hodgkin lymphoma and DLBCL.
Topics: Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Cyclophosphamide; Dacarbazine; Doxorubicin; Etoposide; Fluorodeoxyglucose F18; Hodgkin Disease; Humans; Positron Emission Tomography Computed Tomography; Prednisone; Procarbazine; Vinblastine; Vincristine
PubMed: 28090622
DOI: No ID Found -
Australian Journal of General Practice Dec 2019
Topics: Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Cyclophosphamide; Dacarbazine; Doxorubicin; Dyspnea; Etoposide; Hematuria; Hepatomegaly; Hodgkin Disease; Humans; Lower Urinary Tract Symptoms; Lymphadenopathy; Male; Marfan Syndrome; Mediastinum; Neoplasm Staging; Pectus Carinatum; Pleural Effusion; Prednisone; Procarbazine; Splenomegaly; Tomography, X-Ray Computed; Vinblastine; Vincristine; Young Adult
PubMed: 31774988
DOI: 10.31128/AJGP-07-19-5019 -
Medicina (Kaunas, Lithuania) 2003Erythema nodosum is the most frequent clinicopathological variant of the panniculitides. The disorder is a cutaneous reaction consisting of inflammatory nodular lesions,... (Comparative Study)
Comparative Study Review
Erythema nodosum is the most frequent clinicopathological variant of the panniculitides. The disorder is a cutaneous reaction consisting of inflammatory nodular lesions, usually located on the lower extremities. It may be associated with a wide variety of diseases, infections, sarcoidosis, rheumatologic diseases, inflammatory bowel diseases, medications and malignancies. Relationship between erythema nodosum and malignant lymphoma is described in the article. A review of the literature suggest that the diagnosis of Hodgkin's and non-Hodgkin's disease should be considered in patients with unexplained erythema nodosum.
Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Child; Cyclophosphamide; Diagnosis, Differential; Doxorubicin; Erythema Induratum; Erythema Nodosum; Etoposide; Female; Hodgkin Disease; Humans; Lymphoma, B-Cell; Lymphoma, Non-Hodgkin; Male; Middle Aged; Paraneoplastic Syndromes; Prednisolone; Prednisone; Pregnancy; Procarbazine; Remission Induction; Vincristine
PubMed: 12794364
DOI: No ID Found -
British Journal of Cancer Jul 2017Hodgkin lymphoma (HL) survivors are at increased risk of second malignancies, but few studies have assessed colorectal cancer (CRC) risk after HL treatment. We assessed...
BACKGROUND
Hodgkin lymphoma (HL) survivors are at increased risk of second malignancies, but few studies have assessed colorectal cancer (CRC) risk after HL treatment. We assessed long-term, subsite-specific CRC risk associated with specific radiation fields and chemotherapy regimens.
METHODS
In a Dutch cohort of 3121 5-year HL survivors treated between 1965 and 1995, subsite-specific CRC incidence was compared with general population rates. Treatment effects were quantified by Cox regression analyses.
RESULTS
After a median follow-up of 22.9 years, 55 patients developed CRC. The standardized incidence ratios (SIR) was 2.4-fold increased (95% confidence interval (95%CI) 1.8-3.2), leading to 5.7 excess cases per 10 000 patient-years. Risk was still increased 30 years after HL treatment (SIR: 2.8; 95%CI: 1.6-4.6). The highest (SIR: 6.5, 95%CI: 3.3-11.3) was seen for transverse colon cancer (15.0 (95%CI: 4.3-40.8) after inverted-Y irradiation). A prescribed cumulative procarbazine dose >4.2 g m was associated with a 3.3-fold higher CRC risk (95%CI: 1.8-6.1) compared to treatment without procarbazine. Patients receiving >4.2 g m procarbazine and infradiaphragmatic radiotherapy had a hazard ratio of 6.8 (95%CI: 3.0-15.6) compared with patients receiving neither treatment, which is significantly higher than an additive joint effect (P=0.004).
CONCLUSIONS
Colorectal cancer surveillance should be considered for HL survivors who received Infradiaphragmatic radiotherapy and a high cumulative procarbazine dose.
Topics: Adult; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Colon; Colorectal Neoplasms; Diaphragm; Doxorubicin; Female; Follow-Up Studies; Hodgkin Disease; Humans; Male; Mechlorethamine; Middle Aged; Neoplasms, Radiation-Induced; Neoplasms, Second Primary; Netherlands; Prednisone; Procarbazine; Rectum; Risk Factors; Survivors; Vinblastine; Vincristine; Young Adult
PubMed: 28632726
DOI: 10.1038/bjc.2017.177 -
The Cochrane Database of Systematic... May 2017There are two different international standards for the treatment of early unfavourable and advanced stage Hodgkin lymphoma (HL): chemotherapy with escalated BEACOPP... (Meta-Analysis)
Meta-Analysis Review
Comparison of first-line chemotherapy including escalated BEACOPP versus chemotherapy including ABVD for people with early unfavourable or advanced stage Hodgkin lymphoma.
BACKGROUND
There are two different international standards for the treatment of early unfavourable and advanced stage Hodgkin lymphoma (HL): chemotherapy with escalated BEACOPP (bleomycin/etoposide/doxorubicin/cyclophosphamide/vincristine/procarbazine/prednisone) regimen and chemotherapy with ABVD (doxorubicin/bleomycin/vinblastine/dacarbazine) regimen.
OBJECTIVES
To determine the advantages and disadvantages of chemotherapy including escalated BEACOPP compared to chemotherapy including ABVD in the treatment of early unfavourable or advanced stage HL as first-line treatment.
SEARCH METHODS
We searched for randomised controlled trials in MEDLINE, CENTRAL and conference proceedings (January 1985 to July 2013 and for the update to March 2017) and Embase (1985 to November 2008). Moreover we searched trial registries (March 2017; www.controlled-trials.com, www.clinicaltrialsregister.eu/ctr-search/search, clinicaltrials.gov, www.eortc.be, www.ghsg.org, www.ctc.usyd.edu.au, www.trialscentral.org/index.html) SELECTION CRITERIA: We included randomised controlled trials examining chemotherapy including at least two cycles of escalated BEACOPP regimens compared with chemotherapy including at least four cycles of ABVD regimens as first-line treatment for patients with early unfavourable stage or advanced stage HL.
DATA COLLECTION AND ANALYSIS
The effect measures we used were hazard ratios (HRs) for overall survival (OS), progression-free survival (PFS) and freedom from first progression.We used risk ratios (RRs) relative risks to analyse harms: treatment-related mortality, secondary malignancies (including myeloid dysplastic syndrome (MDS) or acute myeloid leukaemia (AML)), infertility and adverse events.Quality of life was not reported in any trial, therefore not analysed. Two review authors independently extracted data and assessed quality of trials.
MAIN RESULTS
We screened 1796 records and identified five eligible trials in total i.e. one trial could be added on the previous review. These trials included only adults (16 to 65 years of age). We included all five trials with 3427 people in the meta-analyses: the HD9 and HD14 trials were co-ordinated in Germany, the HD2000 and GSM-HD trials were performed in Italy and the EORTC 20012 was conducted in Belgium. The overall risk of performance and detection bias was low for overall survival (OS), but was high for other outcomes, as therapy blinding was not feasible. The remaining 'Risk of bias' domains were low and unclear.All trials reported results for OS and progression-free survival (PFS). In contrast to the our first published review (2011) the addition of results from the EORTC 20012 BEACOPP escalated increases OS (3142 participants; HR 0.74 (95% confidence interval (CI) 0.57 to 0.97; high-quality evidence). This means that only 90 (70 to 117) patients will die after five years in the BEACOPP escalated arm compared to 120 in the ABVD arm. This survival advantage is also reflected in an increased PFS with BEACOPP escalated (3142 participants; HR 0.54 (95% CI 0.45 to 0.64); moderate-quality evidence), meaning that after five years only 144 (121 to 168) patients will experience a progress, relapse or death in the BEACOPP escalated arm compared to 250 in the ABVD arm.There is no evidence for a difference for treatment-related mortality (2700 participants, RR 2.15 (95% CI = 0.93 to 4.95), low-quality evidence).Although the occurrence of MDS or AML may increase with BEACOPP escalated (3332 participants, RR 3.90 (95% CI 1.36 to 11.21); low-quality evidence)), there is no evidence for a difference between both regimens for overall secondary malignancies (3332 participants, RR 1.00 (95% CI 0.68 to 1.48), low-quality evidence). However, the observation time of the studies included in the review is too short to be expected to demonstrate differences with respect to second solid tumours which would not be expected to show significance until around 15 years after treatment.We are very uncertain how many female patients will be infertile due to chemotherapy and which arm might be favoured (106 participants, RR 1.37 (95% CI 0.83 to 2.26), very low-quality evidence). This is a very small sample, and the age of the patients was not detailed. No analysis of male fertility was provided.Five trials reported adverse events and the analysis shows that the escalated BEACOPP regimens probably causes more haematological toxicities WHO grade III or IV ((anaemia: 2425 participants, RR 10.67 (95% CI 7.14 to 15.93); neutropenia: 519 participants, RR 1.80 (95% CI 1.52 to 2.13); thrombocytopenia: 2425 participants, RR 18.12 (95% CI 11.77 to 27.92); infections: 2425 participants, RR 3.73 (95% CI 2.58 to 5.38), all low-quality evidence).Only one trial (EORTC 20012) planned to assess quality of life, however, no results were reported.
AUTHORS' CONCLUSIONS
This meta-analysis provides moderate- to high-quality evidence that adult patients between 16 and 60 years of age with early unfavourable and advanced stage HL benefit regarding OS and PFS from first-line chemotherapy including escalated BEACOPP. The proven benefit in OS for patients with advanced HL is a new finding of this updated review due to the inclusion of the results from the EORTC 20012 trial. Furthermore, there is only low-quality evidence of a difference in the total number of secondary malignancies, as the follow-up period might be too short to detect meaningful differences. Low-quality evidence also suggests that people treated with escalated BEACOPP may have a higher risk to develop secondary AML or MDS. Due to the availability of only very low-quality evidence available, we are unable to come to a conclusion in terms of infertility. This review does for the first time suggest a survival benefit. However, it is clear from this review that BEACOPP escalated may be more toxic that ABVD, and very important long-term side effects of second malignancies and infertility have not been sufficiently analysed yet.
Topics: Adolescent; Adult; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Cyclophosphamide; Dacarbazine; Disease Progression; Doxorubicin; Etoposide; Hodgkin Disease; Humans; Middle Aged; Prednisone; Procarbazine; Randomized Controlled Trials as Topic; Vinblastine; Vincristine; Young Adult
PubMed: 28541603
DOI: 10.1002/14651858.CD007941.pub3