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Expert Review of Hematology Aug 2020To assess evidence on the safety and efficacy of ABVD (doxorubicin [Adriamycin®], bleomycin, vinblastine, and dacarbazine), BEACOPP (bleomycin, etoposide, doxorubicin,... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
To assess evidence on the safety and efficacy of ABVD (doxorubicin [Adriamycin®], bleomycin, vinblastine, and dacarbazine), BEACOPP (bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone), and A+AVD (brentuximab vedotin, with doxorubicin, vinblastine, and dacarbazine) for advanced-stage Hodgkin lymphoma (HL).
METHODS
A systematic literature review (SLR) was conducted on 29 July 2016 (updated 26 July 2018) to identify randomized controlled trials (RCTs) and non-RCTs assessing the treatment of newly-diagnosed advanced-stage HL with ABVD and BEACOPP (and their variants), and A+AVD.
RESULTS
The SLR identified 62 RCTs and 42 non-RCTs. Five-year overall survival rates for ABVD and BEACOPP were 60-97% and 84-99%, and 5-year progression-free survival rates were 58-81% and 83-96%, respectively. Both regimens were associated with tolerability issues and side effects. Discontinuation or dose reduction of bleomycin resulted in fewer adverse events, without significantly affecting efficacy. A head-to-head trial demonstrated improved efficacy for A+AVD vs ABVD, with an acceptable tolerability profile. No data from head-to-head trials comparing A+AVD with BEACOPP were available, and an indirect treatment comparison was not feasible.
CONCLUSION
New therapies, such as A+AVD, maintain the efficacy observed with current treatments, and may provide a more tolerable treatment option for patients with advanced-stage HL.
Topics: Age Factors; Antineoplastic Combined Chemotherapy Protocols; Clinical Trials as Topic; Diagnostic Imaging; Disease Management; Hodgkin Disease; Humans; Neoplasm Staging; Prognosis; Publication Bias; Randomized Controlled Trials as Topic; Treatment Outcome
PubMed: 32749937
DOI: 10.1080/17474086.2020.1793666 -
Cancer Treatment Reviews Feb 2016Childhood cancer survivors (CCS) are at increased risk of developing subsequent malignant neoplasms, including gastrointestinal (GI) cancer. We performed a systematic... (Review)
Review
BACKGROUND
Childhood cancer survivors (CCS) are at increased risk of developing subsequent malignant neoplasms, including gastrointestinal (GI) cancer. We performed a systematic review to summarize all available literature on the risk of, risk factors for, and outcome after subsequent GI cancer among CCS.
METHODS
A systematic search of the literature databases Medline/PubMed (1945-2014) and Embase (1947-2014) was performed to identify studies that consisted of ⩾1000 CCS and assessed incidence of or mortality from subsequent GI cancer as an outcome.
RESULTS
A total of 45 studies were included. Studies that reported risk measures for subsequent GI cancer compared to the general population showed a 3.2 to 9.7-fold elevated risk in cohort studies including all childhood cancer types. Abdominal radiotherapy was associated with an increased risk of subsequent GI cancer in all four studies that assessed this risk. Survivors who had received procarbazine and platinum agents were also suggested to be at increased risk.
CONCLUSION
Abdominal radiotherapy is a risk factor for developing a subsequent GI cancer. Few studies examined detailed treatment-related risk factors and most studies had small number of GI cancer cases. Therefore, no conclusions could be drawn on the effect of time since childhood cancer on GI cancer risk and on outcome after a subsequent GI cancer. Additional research is necessary to further explore risk factors for and outcome after a subsequent GI cancer, and to systematically evaluate the harms and benefits of GI screening among high-risk survivors in order to give sound screening recommendations.
Topics: Abdomen; Adult; Antineoplastic Agents; Child; Early Detection of Cancer; Gastrointestinal Neoplasms; Humans; Incidence; Platinum; Procarbazine; Radiotherapy; Risk Assessment; Risk Factors; Survivors
PubMed: 26827697
DOI: 10.1016/j.ctrv.2015.12.002 -
Scientific Reports Jan 2024We aimed to summarize the cancer risk among patients with indication of group I pharmaceuticals as stated in monographs presented by the International Agency for... (Meta-Analysis)
Meta-Analysis
We aimed to summarize the cancer risk among patients with indication of group I pharmaceuticals as stated in monographs presented by the International Agency for Research on Cancer working groups. Following the PRISMA guidelines, a comprehensive literature search was conducted using the PubMed database. Pharmaceuticals with few studies on cancer risk were identified in systematic reviews; those with two or more studies were subjected to meta-analysis. For the meta-analysis, a random-effects model was used to calculate the summary relative risks (SRRs) and 95% confidence intervals (95% CIs). Heterogeneity across studies was presented using the Higgins I square value from Cochran's Q test. Among the 12 group I pharmaceuticals selected, three involved a single study [etoposide, thiotepa, and mustargen + oncovin + procarbazine + prednisone (MOPP)], seven had two or more studies [busulfan, cyclosporine, azathioprine, cyclophosphamide, methoxsalen + ultraviolet (UV) radiation therapy, melphalan, and chlorambucil], and two did not have any studies [etoposide + bleomycin + cisplatin and treosulfan]. Cyclosporine and azathioprine reported increased skin cancer risk (SRR = 1.32, 95% CI 1.07-1.62; SRR = 1.56, 95% CI 1.25-1.93) compared to non-use. Cyclophosphamide increased bladder and hematologic cancer risk (SRR = 2.87, 95% CI 1.32-6.23; SRR = 2.43, 95% CI 1.65-3.58). Busulfan increased hematologic cancer risk (SRR = 6.71, 95% CI 2.49-18.08); melphalan was associated with hematologic cancer (SRR = 4.43, 95% CI 1.30-15.15). In the systematic review, methoxsalen + UV and MOPP were associated with an increased risk of skin and lung cancer, respectively. Our results can enhance persistent surveillance of group I pharmaceutical use, establish novel clinical strategies for patients with indications, and provide evidence for re-categorizing current group I pharmaceuticals into other groups.
Topics: Humans; Etoposide; Methoxsalen; Azathioprine; Melphalan; Busulfan; Neoplasms; Hematologic Neoplasms; Cyclophosphamide; Cyclosporins; Pharmaceutical Preparations
PubMed: 38172159
DOI: 10.1038/s41598-023-50602-6 -
Canadian Anaesthetists' Society Journal Jul 1983Agents commonly used in the treatment of neoplastic diseases may impair pulmonary function, and a wide spectrum of agents are currently implicated as toxic to the... (Review)
Review
Agents commonly used in the treatment of neoplastic diseases may impair pulmonary function, and a wide spectrum of agents are currently implicated as toxic to the pulmonary system. Agents most commonly implicated are bleomycin, carmustine, busulfan, methotrexate, and thoracic radiotherapy. Less commonly implicated agents include mitomycin, procarbazine, melphalan, chlorambucil, and cyclophosphamide. Therapeutic interactions at time of operation and postoperatively may exacerbate existing pulmonary damage. It is imperative for the physicians treating patients receiving antineoplastic therapy to recognize potentially dangerous therapeutic interactions, and adjust the therapeutic regimen accordingly. Concentrations of inspired oxygen must be maintained as low as is safely possible. Intraoperative monitoring of arterial and mixed venous oxygen tensions will enable the clinician to adjust inspired oxygen concentrations to the lowest possible level while maintaining adequate oxygen tensions to the tissues. A systematic review of antineoplastic agents currently implicated, drug-oxygen interactions, and a review of the pathophysiology are presented.
Topics: Anesthesia; Antineoplastic Agents; Humans; Intraoperative Care; Lung; Oxygen; Oxygen Inhalation Therapy; Postoperative Care; Postoperative Complications; Pulmonary Fibrosis
PubMed: 6347353
DOI: 10.1007/BF03007863 -
Cancer Treatment Reviews Feb 2017Anti-cancer treatment may reduce the fertile life span and induce premature menopause. This review aims to provide an overview of the available literature on effects of... (Review)
Review
BACKGROUND
Anti-cancer treatment may reduce the fertile life span and induce premature menopause. This review aims to provide an overview of the available literature on effects of chemotherapy only on the incidence of ovarian dysfunction and to evaluate the relationship between dose of chemotherapy, age at time of treatment, and time since treatment in female survivors of childhood and young adult cancer.
METHODS
A comprehensive search of electronic databases was performed (search date December 2015).
RESULTS
45 studies were included, describing, in total, 5607 female survivors. Median age at menopause was earlier in cancer survivors than in the general population. The prevalence of amenorrhoea varied from 0% to 83%. Those exposed to MVPP protocols were at highest risk for amenorrhoea (39-79%), as were breast cancer survivors receiving cyclophosphamide-containing regimens, in whom the prevalence of amenorrhoea was 40-80%. The most important risk factors for ovarian dysfunction were: (1) alkylating agents, specifically procarbazine and busulfan, (2) older age at treatment.
CONCLUSION
Breast cancer survivors, those treated with procarbazine or other alkylating agents and those with a higher age at diagnosis are at highest risk of diminished ovarian function. However, all studies included in this review showed methodological limitations. It is imperative that nation-wide registries guarantee long term follow-up during the adult life of cancer survivors.
Topics: Age Factors; Amenorrhea; Antineoplastic Agents; Antineoplastic Agents, Alkylating; Breast Neoplasms; Busulfan; Female; Humans; Menopause; Neoplasms; Ovary; Procarbazine; Survivors
PubMed: 28056411
DOI: 10.1016/j.ctrv.2016.11.006 -
The Cochrane Database of Systematic... Aug 2011There 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
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 provide an evidence-based answer regarding the advantages and disadvantages of chemotherapy including escalated BEACOPP compared to chemotherapy including ABVD.
SEARCH STRATEGY
We searched for randomised controlled trials in MEDLINE, CENTRAL and conference proceedings (January 1985 to November 2010) and EMBASE (1985 to November 2008).
SELECTION CRITERIA
We included randomised controlled trials examining chemotherapy including at least two cycles of escalated BEACOPP regimens compared to 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
Effect measures used were hazard ratios (HR) for overall survival (OS), progression-free survival (PFS) and freedom from first progression. Relative risks were used to analyse complete response rate, treatment-related mortality and adverse events. Two independent review authors extracted data and assessed quality of trials.
MAIN RESULTS
A total of 790 records were screened. Five eligible trials (four published, one ongoing), were identified. These trials included only adult patients (16 to 60 years of age). Four trials with 2868 patients were included in the meta-analyses: the HD9 and HD14 trials from Germany, the HD2000 and GSM-HD trials from Italy. All trials reported results for PFS and OS. PFS was statistically significantly longer for escalated BEACOPP: HR was 0.53 (95% confidence interval (CI) 0.44 to 0.64, I(2) = 0%). There was no statistically significant difference in OS between the comparators: HR was 0.80 (95% CI 0.59 to 1.09, I(2) = 0%). Three trials reported adverse events: the escalated BEACOPP regimens caused statistically significantly more haematological toxicities WHO grade III or IV (anaemia P < 0.00001, neutropenia P = 0.007, thrombocytopenia P < 0.00001), infections (P < 0.00001)) and occurrence of myeloid dysplastic syndrome (MDS) or acute myeloid leukemia (AML) (P = 0.05). There were no differences between both regimens for secondary malignancies, treatment-related mortality or infertility.
AUTHORS' CONCLUSIONS
This meta-analysis showed that adult patients between 16 and 60 years of age with early unfavourable or advanced stage HL benefited from chemotherapy including escalated BEACOPP regarding PFS, but there was no significant difference in OS. Longer follow-up and the inclusion of the EORTC 20012 trial will lead to a more definitive answer with respect to OS.
Topics: Adolescent; Adult; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Cyclophosphamide; Dacarbazine; Doxorubicin; Etoposide; Hodgkin Disease; Humans; Middle Aged; Prednisone; Procarbazine; Randomized Controlled Trials as Topic; Vinblastine; Vincristine; Young Adult
PubMed: 21833963
DOI: 10.1002/14651858.CD007941.pub2 -
The Canadian Journal of Neurological... Nov 2007This systematic review examines the role of chemotherapy following surgery and external beam radiotherapy for adults with newly diagnosed malignant glioma. (Review)
Review
OBJECTIVE
This systematic review examines the role of chemotherapy following surgery and external beam radiotherapy for adults with newly diagnosed malignant glioma.
METHODS
MEDLINE, EMBASE, and the Cochrane Library databases were searched to August 2006 to identify relevant randomized controlled trials (RCTs) and meta-analyses. Proceedings from the 1997 to 2006 annual meetings of the American Society of Clinical Oncology were also searched.
RESULTS
Two RCTs reported a survival advantage in favour of radiotherapy with concomitant and adjuvant temozolomide compared with radiotherapy alone in patients with anaplastic astrocytoma or glioblastoma. Twenty-six RCTs and two meta-analyses detected either no advantage or a small survival advantage in favour of adjuvant chemotherapy.
CONCLUSION
Concomitant temozolomide during radiotherapy and post-radiation adjuvant temozolomide is recommended for all patients ages 18-70 with newly diagnosed glioblastoma multiforme who are fit for radical therapy (ECOG 0-1). Temozolomide may be considered in other situations (i.e., ECOG 2, biopsy only, age > 70, intermediate grade glioma), but there is no high-level evidence to support this decision. Moreover, there are few data on long-term toxicities or quality of life with temozolomide. Adjuvant chemotherapy may be an option for younger patients with anaplastic (grade 3) astrocytoma and patients with pure or mixed oligodendroglioma. However, there is no evidence of a survival advantage from adjuvant chemotherapy in these patients, and treatment-related adverse effects and their impact upon quality of life are poorly studied. The combination of procarbazine, lomustine, and vincristine (PCV) is not recommended for patients with anaplastic oligodendroglioma and oligoastrocytoma.
Topics: Brain Neoplasms; Chemotherapy, Adjuvant; Combined Modality Therapy; Glioma; Humans; Meta-Analysis as Topic; Radiotherapy; Randomized Controlled Trials as Topic
PubMed: 18062446
DOI: 10.1017/s0317167100007265 -
Journal of Neuro-oncology Jul 2014What is the impact of cytotoxic chemotherapy on disease control and survival in the adult patient with progressive glioblastoma? (Review)
Review
QUESTION
What is the impact of cytotoxic chemotherapy on disease control and survival in the adult patient with progressive glioblastoma?
TARGET POPULATION
This recommendation applies to adults patients with progressive glioblastoma.
RECOMMENDATIONS LEVEL II
Temozolomide is recommended as superior to procarbazine in patients with first relapse of glioblastoma after having received nitrosourea chemotherapy or no prior cytotoxic chemotherapy at the time of initial therapy. The use of BCNU-impregnated biodegradable polymer wafers is recommended in the management of progressive glioblastoma as a surgical adjunct when cytoreductive surgery is indicated, taking into account the associated toxicities seen with this modality.
LEVEL III
Consideration of a variety of cytotoxic chemotherapy agents of uncertain benefit is recommended in the setting of progressive glioblastoma based on the judgment of the treating physician taking into account the individual patients prior treatment exposure, systemic health, and likelihood of tolerance of the toxicities of any given agent. It is recommended in such cases that enrollment in available clinical trials be encouraged.
Topics: Absorbable Implants; Adult; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Brain Neoplasms; Carmustine; Chemotherapy, Adjuvant; Dacarbazine; Disease Progression; Evidence-Based Medicine; Glioblastoma; Humans; Temozolomide
PubMed: 24740194
DOI: 10.1007/s11060-013-1338-5 -
Clinical & Translational Oncology :... Jun 2021Considering the increased cancer patient survivorship, the focus is now on addressing the impacts of treatment on quality of life. In young people, altered reproductive...
PURPOSE
Considering the increased cancer patient survivorship, the focus is now on addressing the impacts of treatment on quality of life. In young people, altered reproductive function is a major issue and its effects in young males are largely neglected by novel research. To improve clinician awareness, we systematically reviewed side effects of chemotherapy for Hodgkin lymphoma (HL) in young males.
METHODS
The review was prospectively registered (PROSPERO N. CRD42019122868). Three databases (Medline via PUBMED, SCOPUS, and Cochrane Library) were searched for studies featuring males aged 13-51-years who underwent chemotherapy for HL using ABVD (Adriamycin® (doxorubicin), bleomycin, vinblastine, and dacarbazine) or BEACOPP (bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisolone) regimens. These chemotherapy regimens were compared against each other using sperm characteristics, FSH, and inhibin B levels to measure fertility levels.
RESULTS
Data were extracted from five studies featuring 1344 patients. 6 months post-ABVD saw marked deterioration in sperm count, further reduced by more cycles (P = 0.05). Patients treated with BEACOPP rather than ABVD were more prone to oligospermia. Receiving fewer cycles of both regimens increased the likelihood of sperm production recovering. Patients treated with 6-8 cycles of BEACOPP did not recover spermiogenesis.
CONCLUSIONS
ABVD and BEACOPP regimens significantly reduce fertility function to varying effects depending on treatment duration. ABVD temporarily causes significant reductions in male fertility, whereas BEACOPP's effects are more permanent. Therefore, clinicians should discuss fertility preservation with male patients receiving infertility-inducing gonadotoxic therapy. Further high-quality studies are required to more adequality describe the risk to fertility by chemotherapy.
Topics: Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Cyclophosphamide; Dacarbazine; Doxorubicin; Etoposide; Fertility; Hodgkin Disease; Humans; Infertility, Male; Male; Prednisone; Procarbazine; Vinblastine; Vincristine
PubMed: 32944834
DOI: 10.1007/s12094-020-02483-8 -
Pediatric Neurosurgery 2022Novel targeted and tailored therapies can substantially improve the prognosis for optic pathway glioma (OPG), especially when implemented in a timely manner. However,...
INTRODUCTION
Novel targeted and tailored therapies can substantially improve the prognosis for optic pathway glioma (OPG), especially when implemented in a timely manner. However, their tremendous potential remains underestimated. Therefore, in this study, we provide an updated overview of the clinical trials, current trends, and future perspectives for OPG's novel therapeutic strategies.
METHODS
We completed an extensive literature review using the PubMed, MEDLINE, and ClinicalTrials.gov databases. We analyzed and reported the data following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines.
RESULTS
Thioguanine, procarbazine, lomustine, and vincristine/vinblastine, as well as cisplatin-etoposide, provided excellent results in advanced-phase trials. Selumetinib and trametinib, two oral MEK inhibitors, have been approved for recurrent or refractory OPGs in association with the angiogenetic inhibitor bevacizumab. Among the mTOR inhibitors, everolimus and sirolimus showed the best results. Stereotactic radiosurgery and proton beam radiation therapy have advantages over conventional radiotherapy regimens. Timely treatment is imperative for acute visual symptoms with evidence of tumor progression. This latest evidence can help define a novel "T-Dimension" for pediatric OPG therapies.
CONCLUSION
The novel "T-Dimension" for pediatric OPGs is based on recent evidence-based treatments, including combination chemotherapy regimens, molecular targeted therapies, stereotactic radiosurgery, and proton beam radiation therapy. Additional clinical trials are essential for validating each of these new therapies.
Topics: Child; Combined Modality Therapy; Glioma; Humans; Lomustine; Radiosurgery; Vincristine
PubMed: 35588700
DOI: 10.1159/000524873