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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 -
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 -
Turkish Neurosurgery 2017Malignant glioma is the most common primary brain tumor in adults and the survival rate has remained very low. Thus, determining the optimal treatment for patients can... (Meta-Analysis)
Meta-Analysis Review
AIM
Malignant glioma is the most common primary brain tumor in adults and the survival rate has remained very low. Thus, determining the optimal treatment for patients can be challenging. To compare the efficacy of common therapies, we performed network meta-analysis to estimate the efficacy and safety among procarbazine, lomustine, vincristine, temozolomide, bevacizumab plus temozolomide, and placebo for patients with malignant glioma.
MATERIAL AND METHODS
Relevant studies (as of March, 2014) were identified by searching PubMed, Embase, and Central databases. The primary endpoint of the analysis was the overall survival (OS) and progression-free survival (PFS) of glioma patients.
RESULTS
Nine trials with a total of 3472 patients were included in our network meta-analyses. Compared with placebo, bevacizumab plus temozolomide was associated with the highest estimates of OS and PFS for 12 and 24 months (12 month OS odds ratio [OR]: 2.44; 95% credibility interval [CrIs]: 0.76-9.69; 24 month OS OR: 2.56; 95% CrIs: 1.12?5.24; 12 month PFS OR: 6.76; 95% CrIs: 2.80?17.34; 24 month PFS OR: 3.69; 95% CrIs: 0.62?28.63). However, bevacizumab plus temozolomide did not significantly improve OS or PFS compared to temozolomide alone.
CONCLUSION
Bevacizumab plus temozolomide combination therapy is not significantly more effective than temozolomide alone in improving survival of glioma patients. Moreover, bevacizumab was associated with higher hematologic toxicities. Bevacizumab should be used with caution in glioma patients. Additional randomized controlled trials are required to confirm this finding.
Topics: Antibodies, Monoclonal, Humanized; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Brain Neoplasms; Disease-Free Survival; Glioma; Humans; Network Meta-Analysis
PubMed: 27337236
DOI: 10.5137/1019-5149.JTN.15462-15.0 -
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 -
The Cochrane Database of Systematic... May 2014Standard care of adjuvant treatment for anaplastic oligodendrogliomas (AO) and anaplastic oligoastrocytomas (AOA) is not yet well defined. The benefit of adjuvant... (Review)
Review
BACKGROUND
Standard care of adjuvant treatment for anaplastic oligodendrogliomas (AO) and anaplastic oligoastrocytomas (AOA) is not yet well defined. The benefit of adjuvant chemotherapy and radiotherapy (RT), given as single modalities or sequentially, is still unclear. Furthermore, insight into the predictive and prognostic impact of various biomarkers is surging.
OBJECTIVES
To compare postoperative sequential RT and chemotherapy to RT alone in adults with newly diagnosed AO or mixed AOA. To evaluate the predictive and prognostic impact of the following biomarkers: codeletion of chromosomes 1p and 19q, O(6)-methylguanine-DNA methyltransferase (MGMT) promotor methylation and isocitrate dehydrogenase (IDH)-1 and -2 mutations.
SEARCH METHODS
We searched the Cochrane Central Register for Controlled Trials (CENTRAL, Issue 1, 2014), MEDLINE (2006 to March week 2, 2014) and EMBASE (2006 to week 11, 2014). We scanned reference lists from relevant studies for any additional articles.
SELECTION CRITERIA
We included randomized controlled trials (RCTs) of adults with AO, AOA or anaplastic astrocytoma (AA) comparing adjuvant treatment of chemotherapy, RT, or sequential chemotherapy and RT. We excluded no specific chemotherapy regimens.
DATA COLLECTION AND ANALYSIS
We critically appraised and extracted data from relevant studies. Based on the differences in participant selection with respect to the definition of AO (two versus three high-risk anaplastic features), the inclusion of AA and sequence of treatment (RT and chemotherapy), we could not consider the results from the three RCTs for meta-analysis.
MAIN RESULTS
Three RCTs, with 931 participants, tested different neoadjuvant treatments: RT alone; sequential RT and procarbazine, lomustine and vincristine (PCV) chemotherapy; PCV chemotherapy alone; and temozolomide chemotherapy alone. None of the studies blinded participants or personnel, and, therefore, are considered at high risk of performance and detection bias. The studies were otherwise at low risk of bias. One study, the European Organisation for Research and Treatment of Cancer (EORTC) trial, demonstrated a statistically significant overall survival (OS) benefit for RT plus PCV, with a median OS of 3.5 years compared with 2.6 years in the RT alone arm (P value = 0.018). This result was reported 10 years after the conclusion of the enrolment, and was not apparent in the original 2008 Cochrane review. Furthermore, with retrospective evaluation of biomarkers, codeletion of complete chromosome arms 1p and 19q and IDH-1 or -2 mutation were independent prognostic factors for OS in two of the RCTs (Radiation Therapy Oncology Group (RTOG) and EORTC), and were predictive for OS in one trial (RTOG). The third trial (NOA-04) evaluated these biomarkers prospectively and found them prognostic for progression-free survival.
AUTHORS' CONCLUSIONS
Early PCV, either before or after RT, appears to improve OS of participants with AO or AOA. Use of biomarkers including codeletion of chromosomes 1p and 19q with or without IDH-1 or -2 mutation identify a subset of people with increased sensitivity to combined PCV and RT. The important role of biomarkers was supported in all of the RCTs examined, and prospective evaluation should be undertaken in future studies. However, PCV was associated with significant grade 3 and 4 toxicities, and whether temozolomide can be substituted for this remains unclear.
Topics: Adult; Astrocytoma; Brain Neoplasms; Chemotherapy, Adjuvant; Humans; Oligodendroglioma; Randomized Controlled Trials as Topic
PubMed: 24833028
DOI: 10.1002/14651858.CD007104.pub2 -
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 -
The Lancet. Oncology Sep 2013Several treatment strategies are available for adults with advanced-stage Hodgkin's lymphoma, but studies assessing two alternative standards of care-increased dose... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Several treatment strategies are available for adults with advanced-stage Hodgkin's lymphoma, but studies assessing two alternative standards of care-increased dose bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone (BEACOPPescalated), and doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD)-were not powered to test differences in overall survival. To guide treatment decisions in this population of patients, we did a systematic review and network meta-analysis to identify the best initial treatment strategy.
METHODS
We searched the Cochrane Library, Medline, and conference proceedings for randomised controlled trials published between January, 1980, and June, 2013, that assessed overall survival in patients with advanced-stage Hodgkin's lymphoma given BEACOPPbaseline, BEACOPPescalated, BEACOPP variants, ABVD, cyclophosphamide (mechlorethamine), vincristine, procarbazine, and prednisone (C[M]OPP), hybrid or alternating chemotherapy regimens with ABVD as the backbone (eg, COPP/ABVD, MOPP/ABVD), or doxorubicin, vinblastine, mechlorethamine, vincristine, bleomycin, etoposide, and prednisone combined with radiation therapy (the Stanford V regimen). We assessed studies for eligibility, extracted data, and assessed their quality. We then pooled the data and used a Bayesian random-effects model to combine direct comparisons with indirect evidence. We also reconstructed individual patient survival data from published Kaplan-Meier curves and did standard random-effects Poisson regression. Results are reported relative to ABVD. The primary outcome was overall survival.
FINDINGS
We screened 2055 records and identified 75 papers covering 14 eligible trials that assessed 11 different regimens in 9993 patients, providing 59 651 patient-years of follow-up. 1189 patients died, and the median follow-up was 5·9 years (IQR 4·9-6·7). Included studies were of high methodological quality, and between-trial heterogeneity was negligible (τ(2)=0·01). Overall survival was highest in patients who received six cycles of BEACOPPescalated (HR 0·38, 95% credibility interval [CrI] 0·20-0·75). Compared with a 5 year survival of 88% for ABVD, the survival benefit for six cycles of BEACOPPescalated is 7% (95% CrI 3-10)-ie, a 5 year survival of 95%. Reconstructed individual survival data showed that, at 5 years, BEACOPPescalated has a 10% (95% CI 3-15) advantage over ABVD in overall survival.
INTERPRETATION
Six cycles of BEACOPPescalated significantly improves overall survival compared with ABVD and other regimens, and thus we recommend this treatment strategy as standard of care for patients with access to the appropriate supportive care.
Topics: Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Cyclophosphamide; Dacarbazine; Doxorubicin; Etoposide; Hodgkin Disease; Humans; Prednisone; Procarbazine; Vinblastine; Vincristine
PubMed: 23948348
DOI: 10.1016/S1470-2045(13)70341-3 -
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 Cochrane Database of Systematic... Apr 2008AO and AOA are known to be chemosensitive tumors. However, the impact of adding chemotherapy to surgery and radiotherapy has not been studied. Also, the value of... (Review)
Review
BACKGROUND
AO and AOA are known to be chemosensitive tumors. However, the impact of adding chemotherapy to surgery and radiotherapy has not been studied. Also, the value of chromosome 1p and 19q deletions as prognostic and predictive markers is only beginning to be defined.
OBJECTIVES
After surgery, to compare radiotherapy (RT) plus chemotherapy versus RT alone (standard of care) in adults with newly diagnosed AO or mixed AOA. To investigate the prognostic and predictive value of loss of heterozygosity of chromosomes 1p and 19q. Outcomes analyzed include overall survival (OS), progression-free survival (PFS), and treatment toxicity greater than or equal to grade 3.
SEARCH STRATEGY
Cochrane Central Register for Controlled Trials (CENTRAL, Issue 4,2006), MEDLINE (1966 to 2006) and EMBASE (1988 to 2006) were searched. Reference lists from relevant studies were scanned for any additional relevant articles.
SELECTION CRITERIA
RCTs of adults with AO or mixed AOA comparing surgery plus RT versus surgery plus RT plus chemotherapy were included. No specific chemotherapy regimens were excluded.
DATA COLLECTION AND ANALYSIS
Relevant studies were critically appraised and data was extracted. Based on the differences in patient selection with respect to the definition of AO (2 versus 3 high risk anaplastic features) and sequence of treatment (RT and chemotherapy), the results from the two RCTs were not able to be considered for meta-analysis.
MAIN RESULTS
Two RCTs have tested surgery plus RT plus early procarbazine, lomustine, and vincristine (PCV) chemotherapy versus surgery plus RT alone. Neither study observed a survival benefit with the addition of early PCV chemotherapy. However, both studies found a statistically significant increase in PFS associated with the administration of PCV chemotherapy before surgery or after surgery and RT, with the benefit ranging from 10 to 11 months. Co-deletion of chromosomes 1p and 19q identifies a favorable subgroup of tumors with better overall survival outcomes. The predictive value of 1p and 19q co-deletions is less clear with one study observing a longer PFS with chemotherapy, while the other study did not.
AUTHORS' CONCLUSIONS
Early PCV chemotherapy in addition to standard treatment of surgery and RT does not improve OS in patients with AO or AOA. However, it does improve PFS. It also is associated with significant toxicities. Tumors with 1p and 19q co-deletions are associated with better OS and may indicate a more chemo-responsive tumor.
Topics: Adult; Astrocytoma; Brain Neoplasms; Chemotherapy, Adjuvant; Humans; Oligodendroglioma; Randomized Controlled Trials as Topic
PubMed: 18425979
DOI: 10.1002/14651858.CD007104 -
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