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Acta Oncologica (Stockholm, Sweden) 2001A systematic review of chemotherapy trials in several tumour types was performed by The Swedish Council of Technology Assessment in Health Care (SBU). The procedures for... (Review)
Review
A systematic review of chemotherapy trials in several tumour types was performed by The Swedish Council of Technology Assessment in Health Care (SBU). The procedures for the evaluation of the scientific literature are described separately (Acta Oncol 2001; 40: 155-65). This synthesis of the literature on chemotherapy in patients with acute myeloid leukaemia (AML) is based on 129 scientific articles: one meta-analysis, 51 randomised trials, 39 prospective and 18 retrospective studies, and 20 other articles. Altogether, 39,557 patients were included in these studies. The conclusions reached can be summarized into the following points: Standard induction therapy for patients with AML, consisting of daunorubicin and ara-C in conventional doses, results in a complete remission (CR) rate of 50-60% in an unselected population and a long-term survival of about 10-20%. The total doses of both ara-C and daunorubicin are of importance for remission duration and in some studies also for survival. High-dose ara-C in the induction therapy prolongs remission duration in randomised trials, but has not been proven to affect long-term survival. It also increases toxicity and is not generally recommended. Idarubicin, another anthracyclin, has been compared with daunorubicin in conjunction with ara-C, resulting in a higher CR rate, especially in younger patients. In a meta-analysis of the five-randomised trials performed, a slight survival advantage was also seen with idarubicin. Yet, there is inconclusive evidence to conclude that idarubicin is superior to daunorubicin, and further trials are needed. Mitoxantrone improves the outcome of induction therapy in comparison with daunorubicin in some randomised studies, but conclusive evidence is still lacking. The addition of etoposide to daunorubicin or mitoxantrone and ara-C has improved CR rates, but has not convincingly improved survival and secondary leukaemias may be induced. New induction treatment strategies are defined by identification of prognostic subgroups. A risk stratification of AML patients as to chromosomal aberrations might be of importance for the choice of therapy. Moreover, the speed and the morphological response to the first induction course are predictive for relapse. However, no prospective randomised studies are as yet published regarding risk-adapted induction therapy. Post-remission dose-intensive chemotherapy prolongs the duration of remission, seemingly most in patients < 60 years. However, the data in support of these conclusions are sparse. A convincing effect on survival has not been shown. Limited data indicate that post-remission maintenance therapy with long-term attenuated chemotherapy prolongs time to recurrence, without evidence for prolongation of survival. Allogeneic bone marrow transplantation is an established practice for consolidation in first remission for young patients with an HLA-matched sibling. It is however not known which patients will really benefit from transplantation as no truly randomised comparison of allogeneic vs autologous transplantation or conventionally-dosed chemotherapy has been performed. Patients with and without an HLA-identical sibling have been compared on the basis of intention-to-treat principles ('genetic randomisation'). The disease-free survival seems to be prolonged in the donor group, due to a lower relapse rate with allogeneic transplantation. A higher procedure-related mortality makes the effects on total survival uncertain. Randomised trials with autologous transplantation vs conventional consolidation show a lower relapse rate and a trend for an improved disease-free survival. In one study, in which an autograft was added to four courses of intensive therapy, there was also a late survival advantage. Thus, the role for intensified post-remission treatment in first complete remission with high-dose chemotherapy followed by allogeneic or autologous marrow or stem cell transplantation requires further studies. Moreover, studies with stratification of therapy according to predictors for prognosis in the individual patient are needed. Allogeneic stem cell transplantation after minimal or reduced myeloablative conditioning ('mini-transplantation' or non-myelo stem cell transplantation) induces a host-vs-graft tolerance and an immune graft-vs-leukaemia effect. This new concept of immunotherapy seems to have a low procedure-related mortality, but long-term effects are unknown and evaluation in controlled clinical studies is required. Patients with relapsed AML can only infrequently achieve long-term remissions with chemotherapy in conventional doses. trolled data indicate that allogeneic transplantation can be a curative treatment for these patients a
Topics: Acute Disease; Adult; Age Factors; Aged; Antineoplastic Combined Chemotherapy Protocols; Bone Marrow Transplantation; Cytarabine; Daunorubicin; Disease-Free Survival; Etoposide; Humans; Leukemia, Myeloid; Middle Aged; Mitoxantrone; Neoplasms, Second Primary; Prognosis; Prospective Studies; Randomized Controlled Trials as Topic; Retrospective Studies; Treatment Outcome
PubMed: 11441935
DOI: 10.1080/02841860151116321 -
The Cochrane Database of Systematic... Aug 2014Kaposi's sarcoma remains the most common cancer in Sub-Saharan Africa and the second most common cancer in HIV-infected patients worldwide. Since the introduction of... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Kaposi's sarcoma remains the most common cancer in Sub-Saharan Africa and the second most common cancer in HIV-infected patients worldwide. Since the introduction of highly active antiretroviral therapy (HAART), there has been a decline in its incidence.However, Kaposi's sarcoma continues to be diagnosed in HIV-infected patients.
OBJECTIVES
To assess the added advantage of chemotherapy plus HAART compared to HAART alone; and the advantages of different chemotherapy regimens in HAART and HAART naive HIV infected adults with severe or progressive Kaposi's sarcoma.
SEARCH METHODS
We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE and , GATEWAY, the WHO Clinical Trials Registry Platform and the US National Institutes of Health's ClinicalTrials.gov for ongoing trials and the Aegis archive of HIV/AIDS for conference abstracts. An updated search was conducted in July 2014.
SELECTION CRITERIA
Randomised trials and observational studies evaluating the effects of any chemotherapeutic regimen in combination with HAART compared to HAART alone, chemotherapy versus HAART, and comparisons between different chemotherapy regimens.
DATA COLLECTION AND ANALYSIS
Two review authors assessed the studies independently and extracted outcome data.We used the risk ratio (RR) with a 95% confidence interval (CI) as the measure of effect.We did not conduct meta-analysis as none of the included trials assessed identical chemotherapy regimens.
MAIN RESULTS
We included six randomised trials and three observational studies involving 792 HIV-infected adults with severe Kaposi's sarcoma.Seven studies included patients with a mix of mild to moderate (T0) and severe (T1) Kaposi's sarcoma. However, this review was restricted to the subset of participants with severe Kaposi's sarcoma disease.Studies comparing HAART plus chemotherapy to HAART alone showed the following: one trial comparing HAART plus doxorubicin,bleomycin and vincristine (ABV) to HAART alone showed a significant reduction in disease progression in the HAART plus ABV group (RR 0.10; 95% CI 0.01 to 0.75, 100 participants); there was no statistically significant reduction in mortality and no difference in adverse events. A cohort study comparing liposomal anthracyclines plus HAART to HAART alone showed a non-statistically significant reduction in Kaposi's sarcoma immune reconstitution inflammatory syndrome in patients that received HAART plus liposomal anthracyclines (RR 0.49; 95% CI 0.16 to 1.55, 129 participants).Studies comparing HAART plus chemotherapy to HAART plus a different chemotherapy regimen showed the following: one trial involving 49 participants and comparing paclitaxel versus pegylated liposomal doxorubicin in patients on HAART showed no difference in disease progression. Another trial involving 46 patients and comparing pegylated liposomal doxorubicin versus liposomal daunorubicin showed no participants with progressive Kaposi's sarcoma disease in either group.Studies comparing different chemotherapy regimens in patients from the pre-HAART era showed the following: in the single RCT comparing liposomal daunorubicin to ABV, there was no significant difference with the use of liposomal daunorubicin compared to ABV in disease progression (RR 0.78; 95% CI 0.34 to 1.82, 227 participants) and overall response rate. Another trial involving 178 participants and comparing oral etoposide versus ABV demonstrated no difference in mortality in either group. A non-randomised trial comparing bleomycin alone to ABV demonstrated a higher median survival time in the ABV group; there was also a non-statistically significant reduction in adverse events and disease progression in the ABV group (RR 11; 95% CI 0.67 to 179.29, 24 participants).An additional non-randomised study showed a non-statistically significant overall mortality benefit from liposomal doxorubicin as compared to conservative management consisting of either bleomycin plus vinblastine, vincristine or single-agent antiretroviral therapy alone (RR 0.93; 95% CI 0.75 to 1.15, 29 participants). The overall quality of evidence can be described as moderate quality. The quality of evidence was downgraded due to the small size of many of the included studies and small number of events.
AUTHORS' CONCLUSIONS
The findings from this review suggest that HAART plus chemotherapy may be beneficial in reducing disease progression compared to HAART alone in patients with severe or progressive Kaposi's sarcoma. For patients on HAART, when choosing from different chemotherapy regimens, there was no observed difference between liposomal doxorubicin, liposomal daunorubicin and paclitaxel.
Topics: Alitretinoin; Antineoplastic Agents; Antiretroviral Therapy, Highly Active; Bleomycin; Doxorubicin; Drug Therapy, Combination; Etoposide; HIV Infections; Humans; Liposomes; Observational Studies as Topic; Randomized Controlled Trials as Topic; Sarcoma, Kaposi; Skin Neoplasms; Tretinoin; Vincristine
PubMed: 25221796
DOI: 10.1002/14651858.CD003256.pub2 -
Medicine Nov 2018Autophagy is a mechanism which relies on lysosomes for clearance and recycling of abnormal proteins or organelles. Many studies have demonstrated that the deregulation... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Autophagy is a mechanism which relies on lysosomes for clearance and recycling of abnormal proteins or organelles. Many studies have demonstrated that the deregulation of autophagy is associated with the development of various diseases including cancer. The use of autophagy inhibitors is an emerging trend in cancer treatment. However, the value of autophagy inhibitors remains under debate. Thus, a meta-analysis was performed, aiming to evaluate the clinical value of autophagy-inhibitor-based therapy.
METHODS
We searched for clinical studies that evaluated autophagy-inhibitor-based therapy in cancer. We extracted data from these studies to evaluate the relative risk (RR) of overall response rate (ORR), 6-month progression-free survival (PFS) rate, and 1-year overall survival (OS) rate.
RESULTS
Seven clinical trials were identified (n = 293). Treatments included 2 combinations of hydroxychloroquine and gemcitabine, 1 combination of hydroxychloroquine and doxorubicin, 1 combination of chloroquine and radiation, 2 combinations of chloroquine, temozolomide, and radiation, and 1 hydroxychloroquine monotherapy. Autophagy-inhibitor-based therapy showed higher ORR (RR: 1.33, 95% confidence interval [CI]: 0.95-1.86, P = .009), PFS (RR: 1.72, 95% CI: 1.05-2.82, P = .000), OS (RR: 1.39, 95% CI: 1.11-1.75, P = .000) values than the therapy without inhibiting autophagy.
CONCLUSION
This meta-analysis showed that autophagy-inhibitor-based therapy has better treatment response compared to chemotherapy or radiation therapy without inhibiting autophagy, which may provide a new strategy for the treatment of cancers.
Topics: Antineoplastic Combined Chemotherapy Protocols; Autophagy; Chloroquine; Clinical Trials as Topic; Dacarbazine; Deoxycytidine; Doxorubicin; Humans; Hydroxychloroquine; Neoplasms; Risk; Temozolomide; Treatment Outcome; Gemcitabine
PubMed: 30431566
DOI: 10.1097/MD.0000000000012912 -
Journal of Cancer Research and... 2018The objective of this study was to perform a systematic review and meta-analysis to evaluate the two most commonly used chemotherapy regimens gemcitabine plus cisplatin... (Comparative Study)
Comparative Study Meta-Analysis
OBJECTIVE
The objective of this study was to perform a systematic review and meta-analysis to evaluate the two most commonly used chemotherapy regimens gemcitabine plus cisplatin (GC) and methotrexate, vinblastine, doxorubicin/adriamycin, and cisplatin (MVAC) regimens for muscle-invasive bladder cancer (MIBC) patients.
METHODS
We searched for all studies investigating GC and MVAC for MIBC patients in PubMed, Web of Knowledge, and the Cochrane Central Search Library. A systematic review and meta-analysis were performed.
RESULTS
Our searches identified 13 studies among 2174 patients. In the meta-analysis, the pathological complete response to GC regimens was superior to MVAC regimens. No significant difference in pathological partial response was found between the two groups. GC regimens were associated with a significant decrease risk in Grade 3-4 neutropenia, mucositis, and febrile neutropenia, but a significant increase risk in Grade 3-4 thrombocytopenia. There was no significant difference in overall survival (OS), disease-specific survival (DSS) and disease-free survival (DFS) when compared GC regimens to MVAC regimens.
CONCLUSIONS
GC regimens significantly improved pathological complete response compared to MVAC regimens. GC regimens were associated with a significant decrease risk in Grade 3-4 neutropenia, mucositis, and febrile neutropenia, but a significant increase risk in Grade 3-4 thrombocytopenia. There was no significant difference in OS, DSS, and DFS when compared the two regimens.
Topics: Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Deoxycytidine; Doxorubicin; Humans; Methotrexate; Muscle Neoplasms; Neoplasm Invasiveness; Prognosis; Survival Rate; Urinary Bladder Neoplasms; Vinblastine; Gemcitabine
PubMed: 30488841
DOI: 10.4103/0973-1482.188434 -
Critical Reviews in Oncology/hematology Jul 2021Doxorubicin represents the mainstay in the upfront treatment of diffuse large B-cell lymphoma (DLBCL) patients. However, its administration is sometimes hampered by the... (Meta-Analysis)
Meta-Analysis Review
Doxorubicin represents the mainstay in the upfront treatment of diffuse large B-cell lymphoma (DLBCL) patients. However, its administration is sometimes hampered by the coexistence of former comorbidities/cardiac issues, especially in the elderly population. Liposome encapsulated drug delivery systems have been adopted to reduce the exposure of normal tissues to the drug, both in solid cancers and lymphomas. Despite claims for lower toxicity, the efficacy of non-pegylated liposome doxorubicin (NPLD) in DLBCL, as compared to standard doxorubicin, has never been established. We systematically reviewed relevant literature of NPLD in lymphoma treatment. Adjusting for age/comorbidities, our metanalysis revealed that the use of combinations including NPLD (R-COMP) were non-inferior in terms of response, overall and progression-free survival to the standard of care (R-CHOP) in overlapping series of DLBCL patients. R-COMP may represent a safe and active option for elderly patients with DLBCL, or for those with some extent of cardiac impairment at baseline.
Topics: Aged; Antibodies, Monoclonal, Murine-Derived; Antineoplastic Combined Chemotherapy Protocols; Cyclophosphamide; Doxorubicin; Humans; Lymphoma, Large B-Cell, Diffuse; Prednisone; Rituximab; Treatment Outcome; Vincristine
PubMed: 34087342
DOI: 10.1016/j.critrevonc.2021.103377 -
British Journal of Haematology Jul 2015This study systematically reviewed and meta-analysed the prognostic value of complete remission status at end-of-treatment (18) F-fluoro-2-deoxy-d-glucose positron... (Meta-Analysis)
Meta-Analysis Review
This study systematically reviewed and meta-analysed the prognostic value of complete remission status at end-of-treatment (18) F-fluoro-2-deoxy-d-glucose positron emission tomography (FDG-PET) in diffuse large B-cell lymphoma (DLBCL) patients treated with rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone (R-CHOP). The systematic PubMed/MEDLINE search yielded seven suitable studies comprising a total of 737 R-CHOP-treated DLBCL patients who were in complete remission at end-of-treatment FDG-PET. Overall, the methodological quality of included studies was reasonable. The disease relapse rate among all patients with complete remission status according to end-of-treatment FDG-PET ranged from 7·0% to 20·0%, with a weighted summary proportion of 13·7%. Five of seven studies reported progression-free survival (PFS) of these patients at various specific time points, i.e., 2-year PFS (n = 1), estimated 3-year PFS (n = 3) and 5-year PFS (n = 1), which was 83%, 85-86·4% and 75%, respectively. Three of seven studies reported overall survival (OS) of these patients at various specific time points, i.e., estimated 3-year OS (n = 2) and estimated 5-year OS (n = 1), which were 90%, 93·6% and 83%, respectively. In conclusion, a non-negligible proportion of R-CHOP-treated DLBCL patients who achieve complete remission according to end-of-treatment FDG-PET experiences disease relapse during follow-up.
Topics: Antibodies, Monoclonal, Murine-Derived; Antineoplastic Combined Chemotherapy Protocols; Cyclophosphamide; Doxorubicin; Fluorodeoxyglucose F18; Humans; Lymphoma, Large B-Cell, Diffuse; Positron-Emission Tomography; Prednisone; Prognosis; Remission Induction; Rituximab; Treatment Outcome; Vincristine
PubMed: 25833790
DOI: 10.1111/bjh.13420 -
The Cochrane Database of Systematic... 2004Studies have reported high tumour response rates for platinum-containing regimens in the treatment of women with metastatic breast cancer. (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Studies have reported high tumour response rates for platinum-containing regimens in the treatment of women with metastatic breast cancer.
OBJECTIVES
To identify and review the evidence from randomised trials comparing platinum-containing chemotherapy regimens with regimens not containing platinum in the management of women with metastatic breast cancer.
SEARCH STRATEGY
The specialised register maintained by the editorial base of the Cochrane Breast Cancer Group was searched on 2nd May 2003 using the codes for "advanced breast cancer", "chemotherapy". Details of the search strategy applied to create the register, and the procedure used to code references, are described in the Cochrane Breast Cancer Group module on The Cochrane Library.
SELECTION CRITERIA
Randomised trials comparing platinum-containing chemotherapy regimens with regimens not containing platinum in women with metastatic breast cancer.
DATA COLLECTION AND ANALYSIS
Studies were assessed for eligibility and quality, and data (from published trials) were extracted by two independent reviewers. Hazard ratios were derived for time-to-event outcomes, where possible, and a fixed effect model was used for meta-analysis. Response rates were analysed as dichotomous variables. Toxicity and quality of life data (not available) were extracted where present.
MAIN RESULTS
Thirteen eligible trials were identified, of which 12 had published time-to-event data. The quality of randomisation was generally not described.Data, based on an estimated 987 deaths in 1377 women, was unable to show a statistically significant difference in favour of platinum-containing regimens. The hazard ratio (HR) for overall survival was 1.00 (95% confidence interval (CI) 0.88 to 1.15, p=0.96), with minor heterogeneity. Results were similar when the analysis was limited to trials in women receiving first line chemotherapy. There was no statistically significant difference in favour of platinum-containing regimens for time to progression (overall HR of 1.06 (95% CI 0.95 to 1.19, p=0.31) although there was marked evidence of heterogeneity (p< 0.0001). There was a statistically significant difference in overall response in favour of platinum-containing regimens (OR 1.47; 95% CI 1.23 to 1.76, p=0.0001). However, there was strong statistical evidence of heterogeneity (p < 0.00010) probably reflecting the varying efficacy of the comparator regimens used in the trials. Heterogeneity may also reflect the differences, and difficulties, in assessing response. Women receiving platinum-containing regimens experienced statistically significant greater toxicity levels for leukopenia, hair loss, nausea and vomiting and anaemia compared with those receiving non-platinum regimens.
REVIEWERS' CONCLUSIONS
In view of the significant excess toxicity, lack of progression or survival benefit and the availability of less toxic active agents it is difficult to justify the use of platinum-containing regimens, particularly as first line treatment for women with metastatic breast cancer in routine clinical practice. Ongoing trials are examining the possibility of synergy between platins and trastuzamab, a monoclonal antibody treatment. No randomised trials containing oxalplatin were identified for the present review.
Topics: Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Carboplatin; Cisplatin; Epirubicin; Female; Humans; Randomized Controlled Trials as Topic
PubMed: 15266482
DOI: 10.1002/14651858.CD003374.pub3 -
The Cochrane Database of Systematic... 2004Studies have reported high tumour response rates for platinum-containing regimens in the treatment of women with metastatic breast cancer. (Review)
Review
BACKGROUND
Studies have reported high tumour response rates for platinum-containing regimens in the treatment of women with metastatic breast cancer.
OBJECTIVES
To identify and review the evidence from randomised trials comparing platinum-containing chemotherapy regimens with regimens not containing platinum in the management of women with metastatic breast cancer.
SEARCH STRATEGY
The specialised register maintained by the editorial base of the Cochrane Breast Cancer Group was searched on 2nd May 2003 using the codes for "advanced breast cancer", "chemotherapy". Details of the search strategy applied to create the register, and the procedure used to code references, are described in the Cochrane Breast Cancer Group module on The Cochrane Library.
SELECTION CRITERIA
Randomised trials comparing platinum-containing chemotherapy regimens with regimens not containing platinum in women with metastatic breast cancer.
DATA COLLECTION AND ANALYSIS
Studies were assessed for eligibility and quality, and data (from published trials) were extracted by two independent reviewers. Hazard ratios were derived for time-to-event outcomes, where possible, and a fixed effect model was used for meta-analysis. Response rates were analysed as dichotomous variables. Toxicity and quality of life data (not available) were extracted where present.
MAIN RESULTS
Thirteen eligible trials were identified, of which 12 had published time-to-event data. The quality of randomisation was generally not described.Data, based on an estimated 987 deaths in 1377 women, was unable to show a statistically significant difference in favour of platinum-containing regimens. The hazard ratio (HR) for overall survival was 1.00 (95% confidence interval (CI) 0.88 to 1.15, p=0.96), with minor heterogeneity. Results were similar when the analysis was limited to trials in women receiving first line chemotherapy. There was no statistically significant difference in favour of platinum-containing regimens for time to progression (overall HR of 1.06 (95% CI 0.95 to 1.19, p=0.31) although there was marked evidence of heterogeneity (p< 0.0001). There was a statistically significant difference in overall response in favour of platinum-containing regimens (OR 1.47; 95% CI 1.23 to 1.76, p=0.0001). However, there was strong statistical evidence of heterogeneity (p < 0.00010) probably reflecting the varying efficacy of the comparator regimens used in the trials. Heterogeneity may also reflect the differences, and difficulties, in assessing response. Women receiving platinum-containing regimens experienced statistically significant greater toxicity levels for leukopenia, hair loss, nausea and vomiting and anaemia compared with those receiving non-platinum regimens.
REVIEWERS' CONCLUSIONS
In view of the significant excess toxicity, lack of progression or survival benefit and the availability of less toxic active agents it is difficult to justify the use of platinum-containing regimens, particularly as first line treatment for women with metastatic breast cancer in routine clinical practice. Ongoing trials are examining the possibility of synergy between platins and trastuzamab, a monoclonal antibody treatment. No randomised trials containing oxalplatin were identified for the present review.
Topics: Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Carboplatin; Cisplatin; Epirubicin; Female; Humans; Randomized Controlled Trials as Topic
PubMed: 15106201
DOI: 10.1002/14651858.CD003374.pub2 -
Annals of Hematology Jul 2013Multiple myeloma (MM) is an incurable disease with a poor survival, which has not been affected even by high-dose chemotherapy. This systematic review was performed to... (Meta-Analysis)
Meta-Analysis Review
Multiple myeloma (MM) is an incurable disease with a poor survival, which has not been affected even by high-dose chemotherapy. This systematic review was performed to assess the efficacy and safety of the novel agent bortezomib for patients with previously untreated MM. We systematically searched biomedical literature databases and identified randomized controlled trials (RCTs) comparing bortezomib with placebo, no bortezomib, or other active agents for patients with previously untreated MM. Overall survival (OS), reported as hazard ratio (HR) with 95% confidence interval (CI), was the primary outcome measure. The secondary outcomes included time to progression (TTP), progression-free survival (PFS), and response rates. Five RCTs involving 2,728 patients were included. Three trials compared bortezomib with no bortezomib, and two compared bortezomib with other active agents (vincristine ± adriamycin-based chemotherapy). All included RCTs had methodological shortcomings, including no or unclear allocation concealment and blinding. Compared with no bortezomib or vincristine-based chemotherapy, the bortezomib-based regimen significantly improved the OS of patients with previously untreated MM. HR was 0.71 (95% CI 0.55-0.93) and 0.77 (95% CI 0.60-0.99), respectively. However, when compared with the vincristine + adriamycin-based regimen, the OS was similar (HR = 0.87, 95% CI 0.57-1.33). TTP, PFS, and response rates were also improved in patients receiving bortezomib-based regimen. However, the risk of peripheral neuropathy was found to be significantly higher. In summary, bortezomib appears to improve survival and response rates of patients with previously untreated MM in spite of higher risk of peripheral neuropathy.
Topics: Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Boronic Acids; Bortezomib; Combined Modality Therapy; Disease Progression; Disease-Free Survival; Doxorubicin; Humans; Multiple Myeloma; Peripheral Nervous System Diseases; Protease Inhibitors; Pyrazines; Randomized Controlled Trials as Topic; Remission Induction; Stem Cell Transplantation; Survival Analysis; Transplantation, Autologous; Vincristine
PubMed: 23455401
DOI: 10.1007/s00277-013-1711-7 -
Cancer Biology & Therapy Jun 2014Ovarian cancer is the leading cause of death among gynecological tumors. Carboplatin/paclitaxel represents the cornerstone of front-line treatment. Instead, there is no... (Meta-Analysis)
Meta-Analysis Review
Ovarian cancer is the leading cause of death among gynecological tumors. Carboplatin/paclitaxel represents the cornerstone of front-line treatment. Instead, there is no consensus for management of recurrent/progressive disease, in which pegylated liposomal doxorubicin (PLD) ± carboplatin is widely used. We performed a systematic review and metaanalysis to evaluate impact of PLD-based compared with no-PLD-based regimens in the ovarian cancer treatment. Data were extracted from randomized trials comparing PLD-based treatment to any other regimens in the January 2000-January 2013 time-frame. Study end-points were overall survival (OS), progression free survival (PFS), response rate (RR), CA125 response, and toxicity. Hazard ratios (HRs) of OS and PFS, with 95% CI, odds ratios (ORs) of RR and risk ratios of CA125 response and grade 3-4 toxicity, were extracted. Data were pooled using fixed and random effect models for selected endpoints. Fourteen randomized trials for a total of 5760 patients were selected and included for the final analysis, which showed no OS differences for PLD-based compared with other regimens (pooled HR: 0.94; 95% CI: 0.88-1.02; P = 0.132) and a significant PFS benefit of PLD-based schedule (HR: 0.91; 95% CI: 0.86-0.96; P = 0.001), particularly in second-line (HR: 0.85; 95% CI: 0.75-0.91) and in platinum-sensitive (HR: 0.83; 95% CI: 0.74-0.94) subgroups. This work confirmed the peculiar tolerability profile of this drug, moreover no difference was observed for common hematological toxicities and for RR, CA125 response. PLD-containing regimens do not improve OS when compared with any other schedule in all phases of disease. A marginal PFS advantage is observed only in platinum-sensitive setting and second-line treatment.
Topics: Antibiotics, Antineoplastic; Disease-Free Survival; Doxorubicin; Female; Humans; Ovarian Neoplasms; Polyethylene Glycols; Proportional Hazards Models; Randomized Controlled Trials as Topic; Treatment Outcome
PubMed: 24658024
DOI: 10.4161/cbt.28557