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Frontiers in Oncology 2021Hepatocellular carcinoma (HCC) is the third most fatal cancer, with a 5-year survival rate of 18%. Standard frontline-therapy is multikinase inhibitors (MKIs), but...
BACKGROUND
Hepatocellular carcinoma (HCC) is the third most fatal cancer, with a 5-year survival rate of 18%. Standard frontline-therapy is multikinase inhibitors (MKIs), but accessibility is still limited, particularly in developing countries. This network meta-analysis (NMA) aimed to compare the efficacy of usual chemotherapy vs MKIs.
METHOD
Randomised-controlled trials (RCTs) comparing any among chemotherapy vs MKIs in treatment-naïve patients with advanced HCCs were identified from MEDLINE and SCOPUS databases. Overall survival (OS) and progression-free survival (PFS) probabilities and times were extracted from Kaplan-Meier curves using Digitizer, and then converted to individual patient time-to-event data. A one-stage mixed-effect survival model was applied to estimate median OS and PFS. A two-stage NMA was applied for the overall response rate and adverse events (AEs) outcome.
RESULTS
A total of 20 RCTs were eligible for NMA. Lenvatinib was the best treatment among single MKIs, with median OS and PFS of 9 and 6.3 months, without significant differences in AEs relative to other MKIs. Median OS and PFS were 0.70 (-0.42, 1.83) and 2.17 (1.41, 2.93) months longer with Lenvatinib than Sorafenib. Among chemotherapy agents, FOLFOX4 had the longest median OS and PFS at 7.9 and 4.3 months, respectively, without significant AEs compared to other chemotherapies. The combination of Sorafenib+Doxorubicin prolonged median OS and PFS to 12.7 and 6.3 months, respectively.
CONCLUSION
Use of the MKIs Lenvatinib or Sorafenib as first line systemic treatment for advanced HCC could be beneficial. However, FOLFOX4 might be the optimal choice in a developing country where the health-care budget is limited.
PubMed: 33869060
DOI: 10.3389/fonc.2021.654020 -
The Cochrane Database of Systematic... 2001Between 10% and 35% of women with operable breast cancer will experience an isolated locoregional recurrence following their primary treatment. There is currently no... (Review)
Review
BACKGROUND
Between 10% and 35% of women with operable breast cancer will experience an isolated locoregional recurrence following their primary treatment. There is currently no good evidence that adjuvant systemic treatment is effective in this situation and there is no standard treatment for women who have such a recurrence.
OBJECTIVES
To investigate whether additional systemic treatment will improve the result of local therapy in regard to relapse-free and overall survival in women with potentially curatively resected loco-regional recurrence following breast cancer, who have not had a previous or synchronous distant metastases.
SEARCH STRATEGY
Searches were done, in the first half of 2001, of the specialised register of the Cochrane Breast Cancer Collaborative Review Group, The Cochrane Library, MEDLINE and EMBASE. In addition, the records of the Early Breast Cancer Trialists' Collaborative Group were checked for any relevant trials. The citations in articles reviewing the treatment of locoregional recurrence of breast cancer were checked.
SELECTION CRITERIA
Randomised controlled trials or trials in which women were allocated to treatment or observation by a quasi-random process (such as alternation or date of birth) were eligible. Our aim was to consider separately women with a first incidence of isolated loco-regional recurrence in the treated breast, the chest wall or the regional lymphnode areas (except clavicular nodes) which can be resected without (R0) or with (R1) microscopically demonstrable residual disease. Women with previous or synchronous distant metastases were to be excluded from this part of the review. The second part of the review was to consider women with inoperable loco-regional recurrence and / or clavicular lymphnode involvement, regardless of previous or synchronous metastases.
DATA COLLECTION AND ANALYSIS
We identified three closed studies in which there were a total of four randomised comparisons of systemic therapy versus observation for women who have received radiotherapy for loco-regional recurrence of breast cancer. One trial assessed Actinomyicin-D and randomised 32 patients in the 1960s and another randomised the same number of women to alpha-interferon versus observation in the early 1980s. The Swiss SAKK trial assessed tamoxifen for "good risk" patients and combination chemotherapy (Vincristine, Doxorubicin and Cyclophosphamide) for "poor risk" patients. It randomised 178 and 50 women respectively during 1982-1991. Where possible, data on relapse-free and overall survival were extracted for these trials and analysed using RevMan 4.1. No attempt was made to pool the results of the studies because of clinical heterogeneity and the small number of randomised patients. Three ongoing trials of chemotherapy versus observation have been identified.
MAIN RESULTS
The trial of 32 women who received either radiotherapy alone or in combination with systemic administration of Actinomycin-D found that chemotherapy improved the local control rate but had no apparent effect on overall survival. The interferon trial, which also included a total of only 32 patients, showed that the addition of alpha-Interferon to local treatment of locoregional recurrent breast cancer had no apparent effect on the further course of the disease. The Swiss SAKK trial of tamoxifen (178 women randomized) found an improvement in disease-free survival but not in overall survival and no results are available for the 50 women randomized into the concurrent trial of chemotherapy. The three ongoing trials of chemotherapy have a total target accrual of nearly 2000 patients.
REVIEWER'S CONCLUSIONS
This systematic review of randomised trials provides insufficient evidence to do other than conclude that the most appropriate form of practice for women with loco-regional recurrence of breast cancer is participation in randomised trials of systemic treatment versus observation.
Topics: Antineoplastic Agents; Breast Neoplasms; Combined Modality Therapy; Dactinomycin; Female; Humans; Interferon-alpha; Neoplasm Recurrence, Local; Randomized Controlled Trials as Topic; Tamoxifen
PubMed: 11687148
DOI: 10.1002/14651858.CD002195 -
The Cochrane Database of Systematic... Jul 2007Although the small intestine represents 75% of the length and over 90% of the mucosal surface of the alimentary tract, it is the site of only about 2% of malignant... (Review)
Review
BACKGROUND
Although the small intestine represents 75% of the length and over 90% of the mucosal surface of the alimentary tract, it is the site of only about 2% of malignant gastrointestinal tumours. Adenocarcinoma is the most common histological subtype, accounting for about 40% of all malignant small intestinal tumours. The infrequent occurrence when compared with malignancies of the stomach and colon is accompanied by non-specific clinical symptoms. The consequences are a significant delay in diagnosis and the finding of advanced, incurable disease at operation. Wide surgical resection of early lesions is the only potentially curative treatment, but it is possible only in a minority of patients. The rare nature of adenocarcinomas of the small intestine has led to a paucity of information about the benefits of adjuvant chemotherapy but there are reports of overall better survival for those patients that receive combination treatment. Most chemotherapy regimens consist of 5-fluorouracil (5-FU), alone or in combination with a variety of other agents like doxorubicin, cisplatin, mitomycin C, cyclophosphamide and oxaliplatin.
OBJECTIVES
To determine the role of adjuvant chemotherapy in the management of adenocarcinoma of the small intestine compared to another adjuvant treatment, a placebo or no other adjuvant treatment.
SEARCH STRATEGY
We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE (1966 to 2006), EMBASE (1974 to 2006), PubMed and CINHAL using the Cochrane highly sensitive search strategy for randomised controlled trials.
SELECTION CRITERIA
Phase III randomised controlled trials comparing post-operative adjuvant chemotherapy for adenocarcinoma of the small intestine with other adjuvant therapies, placebo or no adjuvant treatment.
DATA COLLECTION AND ANALYSIS
No suitable trials were identified.
MAIN RESULTS
No studies fulfilled the inclusion criteria.
AUTHORS' CONCLUSIONS
There is a need for high quality randomised controlled trials to evaluate the effectiveness of adjuvant chemotherapy in the management of adenocarcinoma of the small intestine.
Topics: Adenocarcinoma; Chemotherapy, Adjuvant; Humans; Intestinal Neoplasms; Intestine, Small
PubMed: 17636789
DOI: 10.1002/14651858.CD005202.pub2 -
Echocardiography (Mount Kisco, N.Y.) Jul 2018Anthracyclines are widely used to treat solid and hematologic malignancies, but are known to cause cardiotoxicity. As more childhood cancer survivors reach adulthood due... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
Anthracyclines are widely used to treat solid and hematologic malignancies, but are known to cause cardiotoxicity. As more childhood cancer survivors reach adulthood due to improvements in oncologic treatments, they become susceptible to late and progressive anthracycline-induced cardiotoxicity. Nonetheless, diagnostic criteria for early detection of cardiac dysfunction are not well defined in children, adolescent, and young adults (CAYA, ages 1-40 years). We present a natural history of the changes in myocardial deformation in CAYA patients after anthracycline therapy.
METHODS
We performed a literature review search between 2001 and 2016 using PubMed with the following search terms: strain (or deformation), torsion (or twist), children (or adolescent or young adult), cardiotoxicity (or dysfunction), and anthracyclines (or doxorubicin). A total of 23 articles were reviewed. Fourteen articles were incorporated in the meta-analysis.
RESULTS
Strain abnormalities are observed at both short-term and long-term follow-up. Global longitudinal strain (GLS) abnormalities are common during or early after chemotherapy, whereas changes in global circumferential strain (GCS) are more significant and consistent on long-term follow-up. Although global radial strain and torsional parameters are also often abnormal late after chemotherapy, there are few studies evaluating these parameters.
CONCLUSION
There are significant abnormalities in GLS and GCS following anthracycline therapy acutely and late after treatment. The prognostic value of these strain abnormalities warrants further investigation.
Topics: Adolescent; Adult; Anthracyclines; Cardiotoxicity; Child; Echocardiography, Three-Dimensional; Heart Ventricles; Humans; Neoplasms; Ventricular Dysfunction; Young Adult
PubMed: 29603386
DOI: 10.1111/echo.13871 -
The Oncologist Dec 2017Prognosis for patients with metastatic soft tissue sarcomas (STS) is dismal, with median overall survival (OS) of 8-12 months. The role of second-line therapy has been... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Prognosis for patients with metastatic soft tissue sarcomas (STS) is dismal, with median overall survival (OS) of 8-12 months. The role of second-line therapy has been inconsistently investigated over the last 20 years. This systematic review and meta-analysis was performed to assess the efficacy of salvage treatment in pretreated adult type STS, gastrointestinal stromal tumor (GIST) excluded.
MATERIAL AND METHODS
PubMed, Web of Science, SCOPUS, EMBASE, CINAHL, and The Cochrane Library were searched for randomized phase II/phase III trials exploring second- or beyond therapy lines in pretreated metastatic STS. Two independent investigators extracted data; the quality of eligible studies was resolved by consensus. Hazard ratio (HR) of death and progression (OS and progression-free survival [PFS]) and odds ratio (OR) for response rate (RR) were pooled in a fixed- or random-effects model according to heterogeneity. Study quality was assessed with the Cochrane's risk of bias tool, and publication bias with funnel plots.
RESULTS
Overall, 10 randomized trials were selected. The pooled HR for death was 0.81 (95% confidence interval [CI] 0.73-0.9). Second-line therapy reduced the risk of progression by 49% (HR = 0.51, 95% CI 0.34-0.76). This translated into an absolute benefit in OS and PFS by 3.3 and 1.6 months, respectively. Finally, RR with new agents or chemotherapy doublets translated from 4.3% to 7.6% (OR = 1.78, 95% CI 1.22-2.50).
CONCLUSION
Better survival is achieved in patients treated with salvage therapies (chemotherapy, as single or multiple agents or targeted biological agents). A 3-months gain in OS and an almost double RR is observed. Second lines also attained a reduction by 50% the risk of progression.
IMPLICATIONS FOR PRACTICE
There is some evidence that salvage therapies after first-line failure are able to improve outcome in metastatic soft tissue sarcoma (STS). Trabectedin, gemcitabine-based therapy, and pazopanib are currently approved drugs used after conventional upfront treatment. This meta-analysis reviews the benefit of new agents used in randomized trials in comparison with no active treatments or older agents for recurrent/progressed STS. The results show that modern drugs confer a statistically significant 3-month benefit in terms of overall survival, and an increase in response rate. Despite a limited improvement in outcome, currently approved second-line therapy should be offered to patients with good performance status.
Topics: Disease-Free Survival; Doxorubicin; Humans; Randomized Controlled Trials as Topic; Salvage Therapy; Sarcoma
PubMed: 28835514
DOI: 10.1634/theoncologist.2016-0474 -
The Cochrane Database of Systematic... Feb 2013Ovarian carcinosarcoma, also known as malignant mixed Mullerian tumour, is a rare malignant gynaecological tumour constituting about 1% or less of all ovarian cancers.... (Review)
Review
BACKGROUND
Ovarian carcinosarcoma, also known as malignant mixed Mullerian tumour, is a rare malignant gynaecological tumour constituting about 1% or less of all ovarian cancers. In over 80% of cases, there is extra-ovarian intra-abdominal spread at diagnosis. The primary treatment has traditionally been surgical cytoreduction followed by radiotherapy and chemotherapy or chemotherapy alone. Regimes have included cisplatin alone; a combination of doxorubicin, ifosfamide, dacarbazine, cyclophosphamide, taxol; and various other combinations. The effectiveness of these various regimens appears to be mixed. Therefore, there is a need to clarify if there is an optimum neoadjuvant or adjuvant therapy after surgical cytoreduction for this rare tumour. Also, it is important to address quality of life (QoL) issues related to treatment, particularly toxicity, as the overall prognosis appears to be poor.
OBJECTIVES
To assess the effectiveness and safety of various adjuvant and neoadjuvant chemotherapy and radiotherapy options or chemotherapy alone in combination with surgery in the management of ovarian carcinosarcoma.
SEARCH METHODS
We searched the Cochrane Gynaecological Cancer Group Trials Register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE and EMBASE up to February 2012. We also searched registers of clinical trials, abstracts of scientific meetings, reference lists of review articles and contacted experts in the field.
SELECTION CRITERIA
We searched for randomised controlled trials (RCTs) that compared neoadjuvant or adjuvant chemotherapy and radiotherapy, or chemotherapy alone, in women with ovarian carcinosarcoma (malignant mixed Mullerian sarcoma of the ovary). We also reviewed non-randomised studies (NRS) for discussion in the absence of RCTs.
DATA COLLECTION AND ANALYSIS
Two review authors independently assessed whether potentially relevant studies met the inclusion criteria. No trials were found and therefore no data were analysed.
MAIN RESULTS
The search strategy identified 297 unique references of which all were excluded.
AUTHORS' CONCLUSIONS
We found no evidence to inform decisions about neoadjuvant and adjuvant chemotherapy and radiotherapy regimens, or chemotherapy alone, for women with ovarian carcinosarcoma. Ideally, an RCT that is multicentre or multinational, or well designed non-randomised studies that use multivariate analysis to adjust for baseline imbalances, are needed to compare treatment modalities and improve current knowledge. Further research in genetic and molecular signalling pathways might improve understanding of this tumour subtype.
Topics: Carcinosarcoma; Chemotherapy, Adjuvant; Female; Humans; Ovarian Neoplasms; Radiotherapy, Adjuvant
PubMed: 23450567
DOI: 10.1002/14651858.CD006246.pub2 -
The Cochrane Database of Systematic... Sep 2017Efficacy and the risk of severe late effects have to be well-balanced in treatment of Hodgkin lymphoma (HL). Late adverse effects include secondary malignancies which... (Meta-Analysis)
Meta-Analysis Review
Optimisation of chemotherapy and radiotherapy for untreated Hodgkin lymphoma patients with respect to second malignant neoplasms, overall and progression-free survival: individual participant data analysis.
BACKGROUND
Efficacy and the risk of severe late effects have to be well-balanced in treatment of Hodgkin lymphoma (HL). Late adverse effects include secondary malignancies which often have a poor prognosis. To synthesise evidence on the risk of secondary malignancies after current treatment approaches comprising chemotherapy and/or radiotherapy, we performed a meta-analysis based on individual patient data (IPD) from patients treated for newly diagnosed HL.
OBJECTIVES
We investigated several questions concerning possible changes in the risk of secondary malignancies when modifying chemotherapy or radiotherapy (omission of radiotherapy, reduction of the radiation field, reduction of the radiation dose, use of fewer chemotherapy cycles, intensification of chemotherapy). We also analysed whether these modifications affect progression-free survival (PFS) and overall survival (OS).
SEARCH METHODS
We searched MEDLINE and Cochrane CENTRAL trials databases comprehensively in June 2010 for all randomised trials in HL since 1984. Key international trials registries were also searched. The search was updated in March 2015 without collecting further IPD (one further eligible study found) and again in July 2017 (no further eligible studies).
SELECTION CRITERIA
We included randomised controlled trials (RCTs) for untreated HL patients which enrolled at least 50 patients per arm, completed recruitment by 2007 and performed a treatment comparison relevant to our objectives.
DATA COLLECTION AND ANALYSIS
Study groups submitted IPD, including age, sex, stage and the outcomes secondary malignant neoplasm (SMN), OS and PFS as time-to-event data. We meta-analysed these data using Petos method (SMN) and Cox regression with inverse-variance pooling (OS, PFS) for each of the five study questions, and performed subgroup and sensitivity analyses to assess the applicability and robustness of the results.
MAIN RESULTS
We identified 21 eligible trials and obtained IPD for 16. For four studies no data were supplied despite repeated efforts, while one study was only identified in 2015 and IPD were not sought. For each study question, between three and six trials with between 1101 and 2996 participants in total and median follow-up between 6.7 and 10.8 years were analysed. All participants were adults and mainly under 60 years. Risk of bias was assessed as low for the majority of studies and outcomes. Chemotherapy alone versus same chemotherapy plus radiotherapy. Omitting additional radiotherapy probably reduces secondary malignancy incidence (Peto odds ratio (OR) 0.43, 95% confidence interval (CI) 0.23 to 0.82, low quality of evidence), corresponding to an estimated reduction of eight-year SMN risk from 8% to 4%. This decrease was particularly true for secondary acute leukemias. However, we had insufficient evidence to determine whether OS rates differ between patients treated with chemotherapy alone versus combined-modality (hazard ratio (HR) 0.71, 95% CI 0.46 to 1.11, moderate quality of evidence). There was a slightly higher rate of PFS with combined modality, but our confidence in the results was limited by high levels of statistical heterogeneity between studies (HR 1.31, 95% CI 0.99 to 1.73, moderate quality of evidence). Chemotherapy plus involved-field radiation versus same chemotherapy plus extended-field radiation (early stages) . There is insufficient evidence to determine whether smaller radiation field reduces SMN risk (Peto OR 0.86, 95% CI 0.64 to 1.16, low quality of evidence), OS (HR 0.89, 95% C: 0.70 to 1.12, high quality of evidence) or PFS (HR 0.99, 95% CI 0.81 to 1.21, high quality of evidence). Chemotherapy plus lower-dose radiation versus same chemotherapy plus higher-dose radiation (early stages). There is insufficient evidence to determine the effect of lower-radiation dose on SMN risk (Peto OR 1.03, 95% CI 0.71 to 1.50, low quality of evidence), OS (HR 0.91, 95% CI 0.65 to 1.28, high quality of evidence) or PFS (HR 1.20, 95% CI 0.97 to 1.48, high quality of evidence). Fewer versus more courses of chemotherapy (each with or without radiotherapy; early stages). Fewer chemotherapy courses probably has little or no effect on SMN risk (Peto OR 1.10, 95% CI 0.74 to 1.62), OS (HR 0.99, 95% CI 0.73 to1.34) or PFS (HR 1.15, 95% CI 0.91 to 1.45).Outcomes had a moderate (SMN) or high (OS, PFS) quality of evidence. Dose-intensified versus ABVD-like chemotherapy (with or without radiotherapy in each case). In the mainly advanced-stage patients who were treated with intensified chemotherapy, the rate of secondary malignancies was low. There was insufficient evidence to determine the effect of chemotherapy intensification (Peto OR 1.37, CI 0.89 to 2.10, low quality of evidence). The rate of secondary acute leukemias (and for younger patients, all secondary malignancies) was probably higher than among those who had treatment with standard-dose ABVD-like protocols. In contrast, the intensified chemotherapy protocols probably improved PFS (eight-year PFS 75% versus 69% for ABVD-like treatment, HR 0.82, 95% CI 0.7 to 0.95, moderate quality of evidence). Evidence suggesting improved survival with intensified chemotherapy was not conclusive (HR: 0.85, CI 0.70 to 1.04), although escalated-dose BEACOPP appeared to lengthen survival compared to ABVD-like chemotherapy (HR 0.58, 95% CI 0.43 to 0.79, moderate quality of evidence).Generally, we could draw valid conclusions only in terms of secondary haematological malignancies, which usually occur less than 10 years after initial treatment, while follow-up within the present analysis was too short to record all solid tumours.
AUTHORS' CONCLUSIONS
The risk of secondary acute myeloid leukaemia and myelodysplastic syndrome (AML/MDS) is increased but efficacy is improved among patients treated with intensified chemotherapy protocols. Treatment decisions must be tailored for individual patients. Consolidating radiotherapy is associated with an increased rate of secondary malignancies; therefore it appears important to define which patients can safely be treated without radiotherapy after chemotherapy, both for early and advanced stages. For early stages, treatment optimisation methods such as use of fewer chemotherapy cycles and reduced field or reduced-dose radiotherapy did not appear to markedly affect efficacy or secondary malignancy risk. Due to the limited amount of long-term follow-up in this meta-analysis, further long-term investigations of late events are needed, particularly with respect to secondary solid tumours. Since many older studies have been included, possible improvement of radiotherapy techniques must be considered when interpreting these results.
Topics: Adult; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Chemoradiotherapy; Dacarbazine; Disease-Free Survival; Doxorubicin; Hodgkin Disease; Humans; Leukemia, Radiation-Induced; Middle Aged; Myelodysplastic Syndromes; Neoplasms, Second Primary; Radiotherapy; Radiotherapy Dosage; Randomized Controlled Trials as Topic; Vinblastine
PubMed: 28901021
DOI: 10.1002/14651858.CD008814.pub2 -
Journal of Gastrointestinal Oncology Apr 2021Gastric cancer progression resulting in metachronous peritoneal metastasizing is almost always associated with an adverse prognosis. This review discusses various... (Review)
Review
Gastric cancer progression resulting in metachronous peritoneal metastasizing is almost always associated with an adverse prognosis. This review discusses various options of preventing metachronous peritoneal metastases in radically operated gastric cancer patients. Also examined are different hyperthermic intraperitoneal chemotherapy (HIPEC) regimens employed in gastric cancer treatment, postoperative morbidity and mortality rates and long-term treatment outcomes. The authors also review their own experience of using HIPEC based on the combination of cisplatin and doxorubicin in doses of 50 mg/m at 42 °C for 1 h to prevent gastric cancer peritoneal dissemination. As a result, progression-free survival rose from 19.6%±5.6% to 47.1%±6.3% (P <0.001) and dissemination-free survival-from 22.7%±6.0% to 51.9%±6.3% (P <0.001). It is noted that the combination of the described HIPEC regimen with systemic chemotherapy helped raise metastases-free 3-year survival rate to up to 91.0%±9.0% (P =0.025) compared with 48.6%±6.4% for patients who underwent only a combined surgery/HIPEC treatment. HIPEC is a promising combined treatment strategy for radically operated gastric cancer patients that can improve patient survival and decrease peritoneal dissemination rate. However, the number of randomized studies on adjuvant HIPEC are still insufficient for a subgroup assessment of efficacy of the given chemotherapy regimens and generation of evidence-based recommendations on the individual use of chemotherapy agents and their combinations, and HIPEC procedural techniques. Further prospective randomized studies are needed to assess the practicability of complementing HIPEC with adjuvant systemic chemotherapies.
PubMed: 33968422
DOI: 10.21037/jgo-20-129 -
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 -
BMC Cancer Jun 2010We conducted a systematic review and meta-analysis to clarify the risk of early and late cardiotoxicity of anthracycline agents in patients treated for breast or ovarian... (Review)
Review
BACKGROUND
We conducted a systematic review and meta-analysis to clarify the risk of early and late cardiotoxicity of anthracycline agents in patients treated for breast or ovarian cancer, lymphoma, myeloma or sarcoma.
METHODS
Randomized controlled trials were sought using comprehensive searches of electronic databases in June 2008. Reference lists of retrieved articles were also scanned for additional articles. Outcomes investigated were early or late clinical and sub-clinical cardiotoxicity. Trial quality was assessed, and data were pooled through meta-analysis where appropriate.
RESULTS
Fifty-five published RCTs were included; the majority were on women with advanced breast cancer. A significantly greater risk of clinical cardiotoxicity was found with anthracycline compared with non-anthracycline regimens (OR 5.43 95% confidence interval: 2.34, 12.62), anthracycline versus mitoxantrone (OR 2.88 95% confidence interval: 1.29, 6.44), and bolus versus continuous anthracycline infusions (OR 4.13 95% confidence interval: 1.75, 9.72). Risk of clinical cardiotoxicity was significantly lower with epirubicin versus doxorubicin (OR 0.39 95% confidence interval: 0.20, 0.78), liposomal versus non-liposomal doxorubicin (OR 0.18 95% confidence interval: 0.08, 0.38) and with a concomitant cardioprotective agent (OR 0.21 95% confidence interval: 0.13, 0.33). No statistical heterogeneity was found for these pooled analyses. A similar pattern of results were found for subclinical cardiotoxicity; with risk significantly greater with anthracycline containing regimens and bolus administration; and significantly lower risk with epirubicin, liposomal doxorubicin versus doxorubicin but not epirubicin, and with concomitant use of a cardioprotective agent. Low to moderate statistical heterogeneity was found for two of the five pooled analyses, perhaps due to the different criteria used for reduction in Left Ventricular Ejection Fraction. Meta-analyses of any cardiotoxicity (clinical and subclinical) showed moderate to high statistical heterogeneity for four of five pooled analyses; criteria for any cardiotoxic event differed between studies. Nonetheless the pattern of results was similar to those for clinical or subclinical cardiotoxicity described above.
CONCLUSIONS
Evidence is not sufficiently robust to support clear evidence-based recommendations on different anthracycline treatment regimens, or for routine use of cardiac protective agents or liposomal formulations. There is a need to improve cardiac monitoring in oncology trials.
Topics: Anthracyclines; Antineoplastic Agents; Female; Heart Diseases; Humans; Meta-Analysis as Topic; Neoplasms; Randomized Controlled Trials as Topic; Treatment Outcome
PubMed: 20587042
DOI: 10.1186/1471-2407-10-337