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Health Technology Assessment... 2002
Review
Topics: Aged; Antineoplastic Agents; Cost-Benefit Analysis; Doxorubicin; Female; Humans; Middle Aged; Outcome Assessment, Health Care; Ovarian Neoplasms; Quality of Life; Randomized Controlled Trials as Topic; State Medicine; Survival; United Kingdom
PubMed: 12433314
DOI: 10.3310/hta6230 -
The Cochrane Database of Systematic... Jul 2022Ovarian cancer is the seventh most frequent cancer diagnosis worldwide, and the eighth leading cause of cancer mortality. Epithelial ovarian cancer is the most common... (Review)
Review
BACKGROUND
Ovarian cancer is the seventh most frequent cancer diagnosis worldwide, and the eighth leading cause of cancer mortality. Epithelial ovarian cancer is the most common kind, accounting for 90% of cases. First-line therapy for women with epithelial ovarian cancer consists of a combination of cytoreductive surgery and platinum and taxane-based chemotherapy. However, more than 50% of women with epithelial ovarian cancer will experience a relapse and require further chemotherapy and at some point develop resistance to platinum-based drugs. Currently, guidance on the use of most chemotherapy drugs, including taxanes, is unclear for women whose epithelial ovarian cancer has recurred. Paclitaxel, topotecan, pegylated liposomal doxorubicin hydrochloride, trabectedin and gemcitabine are all licensed for use in the UK at the discretion of clinicians, following discussion with the women as to potential adverse effects. Taxanes can be given in once-weekly regimens (at a lower dose) or three-weekly regimens (at a higher dose), which may have differences in the severity of side effects and effectiveness. As relapsed disease suggests incurable disease, it is all the more important to consider side effects and the impact of treatment schedules, as well as quality of life, and not only the life-prolonging effects of treatment.
OBJECTIVES
To assess the efficacy and toxicity of different taxane monotherapy regimens for women with recurrent epithelial ovarian, tubal or primary peritoneal cancer.
SEARCH METHODS
We searched CENTRAL, MEDLINE and Embase, up to 22 March 2022. Other related databases and trial registries were searched as well as grey literature and no additional studies were identified. A total of 1500 records were identified.
SELECTION CRITERIA
We included randomised controlled trials of taxane monotherapy for adult women diagnosed with recurrent epithelial ovarian, tubal or primary peritoneal cancer, previously treated with platinum-based chemotherapy. We included trials comparing two or more taxane monotherapy regimens. Participants could be experiencing their first recurrence of disease or any line of recurrence.
DATA COLLECTION AND ANALYSIS
Two review authors screened, independently assessed studies, and extracted data from the included studies. The clinical outcomes we examined were overall survival, response rate, progression-free survival, neurotoxicity, neutropenia, alopecia, and quality of life. We performed statistical analyses using fixed-effect and random-effects models following standard Cochrane methodology. We rated the certainty of evidence according to the GRADE approach.
MAIN RESULTS
Our literature search yielded 1500 records of 1466 studies; no additional studies were identified by searching grey literature or handsearching. We uploaded the search results into Covidence. After the exclusion of 92 duplicates, we screened titles and abstracts of 1374 records. Of these, we identified 24 studies for full-text screening. We included four parallel-group randomised controlled trials (RCTs). All trials were multicentred and conducted in a hospital setting. The studies included 981 eligible participants with recurrent epithelial ovarian cancer, tubal or primary peritoneal cancer with a median age ranging between 56 to 62 years of age. All participants had a WHO (World Health Organization) performance status of between 0 to 2. The proportion of participants with serous histology ranged between 56% to 85%. Participants included women who had platinum-sensitive (71%) and platinum-resistant (29%) relapse. Some participants were taxane pre-treated (5.6%), whilst the majority were taxane-naive (94.4%). No studies were classified as having a high risk of bias for any of the domains in the Cochrane risk of bias tool. We found that there may be little or no difference in overall survival (OS) between weekly paclitaxel and three-weekly paclitaxel, but the evidence is very uncertain (risk ratio (RR) of 0.94, 95% confidence interval (CI) 0.66 to 1.33, two studies, 263 participants, very low-certainty evidence). Similarly, there may be little or no difference in response rate (RR of 1.07, 95% CI 0.78 to 1.48, two studies, 263 participants, very low-certainty evidence) and progression-free survival (PFS) (RR of 0.83, 95% CI 0.46 to 1.52, two studies, 263 participants, very low-certainty evidence) between weekly and three-weekly paclitaxel, but the evidence is very uncertain. We found differences in the chemotherapy-associated adverse events between the weekly and three-weekly paclitaxel regimens. The weekly paclitaxel regimen may result in a reduction in neutropenia (RR 0.51, 95% 0.27 to 0.95, two studies, 260 participants, low-certainty evidence) and alopecia (RR 0.58, 95% CI 0.46 to 0.73, one study, 205 participants, low-certainty evidence). There may be little or no difference in neurotoxicity, but the evidence was very low-certainty and we cannot exclude an effect (RR 0.53, 95% CI 0.19 to 1.45, two studies, 260 participants). When examining the effect of paclitaxel dosage in the three-weekly regimen, the 250 mg/m paclitaxel regimen probably causes more neurotoxicity compared to the 175 mg/m regimen (RR 0.41, 95% CI 0.21 to 0.80, one study, 330 participants, moderate-certainty evidence). Quality-of-life data were not extractable from any of the included studies.
AUTHORS' CONCLUSIONS
Fewer people may experience neutropenia when given weekly rather than three-weekly paclitaxel (low-certainty evidence), although it may make little or no difference to the risk of developing neurotoxicity (very low-certainty evidence). This is based on the participants receiving lower doses of drug more often. However, our confidence in this result is low and the true effect may be substantially different from the estimate of the effect. Weekly paclitaxel probably reduces the risk of alopecia, although the rates in both arms were high (46% versus 79%) (low-certainty evidence). A change to weekly from three-weekly chemotherapy could be considered to reduce the likelihood of toxicity, as it may have little or no negative impact on response rate (very low-certainty evidence), PFS (very low-certainty evidence) or OS (very low-certainty evidence). Three-weekly paclitaxel, given at a dose of 175 mg/m compared to a higher dose,probably reduces the risk of neurotoxicity.We are moderately confident in this result; the true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different. A change to 175 mg/m paclitaxel (from a higher dose), if a three-weekly regimen is used, probably has little or no negative impact on PFS or OS (very low-certainty evidence).
Topics: Adult; Alopecia; Bridged-Ring Compounds; Carcinoma, Ovarian Epithelial; Female; Humans; Middle Aged; Neoplasm Recurrence, Local; Neutropenia; Ovarian Neoplasms; Paclitaxel; Taxoids
PubMed: 35866378
DOI: 10.1002/14651858.CD008766.pub3 -
The Oncologist 2013CD30(+) lymphoproliferative disorders represent a spectrum of diseases with distinct clinical phenotypes ranging from reactive conditions to aggressive systemic... (Review)
Review
CD30(+) lymphoproliferative disorders represent a spectrum of diseases with distinct clinical phenotypes ranging from reactive conditions to aggressive systemic anaplastic lymphoma kinase (ALK)(-) anaplastic large cell lymphoma (ALCL). In January 2011, the U.S. Food and Drug Administration (FDA) announced a possible association between breast implants and ALCL, which was likened to systemic ALCL and treated accordingly. We analyzed existing data to see if implant-associated ALCL (iALCL) may represent a distinct entity, different from aggressive ALCL. We conducted a systematic review of publications regarding ALCL and breast implantation for 1990-2012 and contacted corresponding authors to obtain long-term follow-up where available. We identified 44 unique cases of iALCL, the majority of which were associated with seroma, had an ALK(-) phenotype (97%), and had a good prognosis, different from the expected 40% 5-year survival rate of patients with ALK(-) nodal ALCL (one case remitted spontaneously following implant removal; only two deaths have been reported to the FDA or in the scientific literature since 1990). The majority of these patients received cyclophosphamide, doxorubicin, vincristine, and prednisolone with or without radiation, but radiation alone also resulted in complete clinical responses. It appears that iALCL demonstrates a strong association with breast implants, a waxing and waning course, and an overall good prognosis, with morphology, cytokine profile, and biological behavior similar to those of primary cutaneous ALCL. Taken together, these data are suggestive that iALCL may start as a reactive process with the potential to progress and acquire an aggressive phenotype typical of its systemic counterpart. A larger analysis and prospective evaluation and follow-up of iALCL patients are necessary to definitively resolve the issue of the natural course of the disease and best therapeutic approaches for these patients.
Topics: Adult; Aged; Aged, 80 and over; Breast Implantation; Female; Humans; Ki-1 Antigen; Lymphoma, Large-Cell, Anaplastic; Lymphoproliferative Disorders; Middle Aged
PubMed: 23429741
DOI: 10.1634/theoncologist.2012-0238 -
Breast Cancer Research and Treatment Nov 2017To compare palbociclib + letrozole and palbociclib + fulvestrant with chemotherapy agents in postmenopausal women with hormone receptor-positive (HR+)/human... (Meta-Analysis)
Meta-Analysis Review
Systematic review and network meta-analysis comparing palbociclib with chemotherapy agents for the treatment of postmenopausal women with HR-positive and HER2-negative advanced/metastatic breast cancer.
PURPOSE
To compare palbociclib + letrozole and palbociclib + fulvestrant with chemotherapy agents in postmenopausal women with hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2-) advanced/metastatic breast cancer (ABC/MBC) who had no prior systemic treatment for advanced disease (first line) or whose disease progressed after prior endocrine therapy or chemotherapy (second line).
METHODS
A systematic search identified randomized controlled trials (RCTs) published from January 2000 to January 2016 that compared endocrine-based therapies, chemotherapy agents, and/or chemotherapy agents + biological therapies in the first- and second-line treatment of postmenopausal women with HR+/HER2- ABC/MBC. The main outcome of interest was progression-free survival (PFS)/time to progression (TTP). Bayesian network meta-analyses (NMAs) and pairwise meta-analyses were conducted. Heterogeneity and inconsistency were assessed.
RESULTS
Sixty RCTs met eligibility criteria and were stratified by line of therapy. In the first line, palbociclib + letrozole showed statistically significant improvements in PFS/TTP versus capecitabine [intermittent: HR 0.28 (95% CrI 0.11-0.72)] and mitoxantrone [HR 0.28 (0.13-0.61)], and trended toward improvements versus paclitaxel [HR 0.59 (0.19-1.96)], docetaxel [HR 0.51 (0.14-2.03)] and other monotherapy or combination agents (HRs ranging from 0.24 to 0.99). In the second line, palbociclib + fulvestrant showed statistically significant improvements in PFS/TTP versus capecitabine [intermittent: HR 0.28 (0.13-0.65)], mitoxantrone [HR 0.26 (0.12-0.53)], and pegylated liposomal doxorubicin [HR 0.19 (0.07-0.50)], and trended toward improvements versus paclitaxel [HR 0.48 (0.16-1.44)], docetaxel [HR 0.71 (0.24-2.13)] and other monotherapy or combination agents (HRs ranging from 0.23-0.89). NMA findings aligned with direct evidence and were robust to sensitivity analyses.
CONCLUSIONS
Palbociclib + letrozole and palbociclib + fulvestrant demonstrate trends in incremental efficacy compared with chemotherapy agents for the first- and second-line treatment of HR +/HER2- ABC/MBC.
Topics: Age Factors; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Disease Progression; Female; Humans; Neoplasm Metastasis; Neoplasm Staging; Piperazines; Postmenopause; Pyridines; Randomized Controlled Trials as Topic; Receptor, ErbB-2; Receptors, Estrogen; Receptors, Progesterone; Retreatment; Survival Analysis; Treatment Outcome
PubMed: 28752187
DOI: 10.1007/s10549-017-4404-4 -
The Cochrane Database of Systematic... Jan 2013This is an update of the original review that was published in The Cochrane Database of Systematic Reviews, 2009, Issue 2. Gestational trophoblastic neoplasia (GTN) are... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
This is an update of the original review that was published in The Cochrane Database of Systematic Reviews, 2009, Issue 2. Gestational trophoblastic neoplasia (GTN) are malignant disorders of the placenta that include invasive hydatidiform mole, choriocarcinoma, placental-site trophoblastic tumour (PSTT) and epithelioid trophoblastic tumour (ETT). Choriocarcinoma and invasive hydatidiform mole respond well to chemotherapy: low-risk tumours are treated with single-agent chemotherapy (e.g. methotrexate or actinomycin D), whereas high-risk tumours are treated with combination chemotherapy (e.g. EMA/CO (etoposide, methotrexate, actinomycin D, cyclophosphamide and vincristine)). Various drug combinations may be used for high-risk tumours; however, the comparative efficacy and safety of these regimens is not clear.
OBJECTIVES
To determine the efficacy and safety of combination chemotherapy in treating high-risk GTN.
SEARCH METHODS
For the original review, we searched the Cochrane Group Specialised Register, Cochrane Central Register of Controlled Trials (CENTRAL; Issue 2, 2008), MEDLINE, EMBASE and CBM in May 2008. For the updated review, we searched Cochrane Group Specialised Register, CENTRAL, MEDLINE and EMBASE to September 2012. In addition, we searched online clinical trial registries for ongoing trials.
SELECTION CRITERIA
Randomised controlled trials (RCTs) and quasi-RCTs comparing first-line combination chemotherapy interventions in women with high-risk GTN.
DATA COLLECTION AND ANALYSIS
Two review authors independently collected data using a data extraction form. Meta-analysis could not be performed as we included only one study.
MAIN RESULTS
We included one RCT of 42 women with high-risk GTN who were randomised to MAC (methotrexate, actinomycin D and chlorambucil) or the modified CHAMOCA regimen (cyclophosphamide, hydroxyurea, actinomycin D, methotrexate, doxorubicin, melphalan and vincristine). There were no statistically significant differences in efficacy of the two regimens; however women in the MAC group experienced statistically significantly less toxicity overall and less haematological toxicity than women in the CHAMOCA group. During the study period, six women in the CHAMOCA group died compared with one in the MAC group. This study was stopped early due to unacceptable levels of toxicity in the CHAMOCA group. We identified no RCTs comparing EMA/CO with MAC or other chemotherapy regimens.
AUTHORS' CONCLUSIONS
CHAMOCA is not recommended for GTN treatment as it is more toxic and not more effective than MAC. EMA/CO is currently the most widely used first-line combination chemotherapy for high-risk GTN, although this regimen has not been rigorously compared to other combinations such as MAC or FAV in RCTs. Other regimens may be associated with less acute toxicity than EMA/CO; however, proper evaluation of these combinations in high-quality RCTs that include long-term surveillance for secondary cancers is required. We acknowledge that, given the low incidence of GTN, RCTs in this field are difficult to conduct, hence multicentre collaboration is necessary.
Topics: Antineoplastic Combined Chemotherapy Protocols; Cyclophosphamide; Dactinomycin; Doxorubicin; Early Termination of Clinical Trials; Female; Gestational Trophoblastic Disease; Humans; Hydatidiform Mole; Hydroxyurea; Leucovorin; Melphalan; Methotrexate; Pregnancy; Trophoblastic Tumor, Placental Site; Vincristine
PubMed: 23440800
DOI: 10.1002/14651858.CD005196.pub4 -
The Cochrane Database of Systematic... Jan 2009Hepatocellular carcinoma is a disease of great concern. Surgery is the treatment of choice, but there is still a high recurrence rate after resection. (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Hepatocellular carcinoma is a disease of great concern. Surgery is the treatment of choice, but there is still a high recurrence rate after resection.
OBJECTIVES
To determine the benefits and harms of neoadjuvant and adjuvant therapies compared to surgery alone or surgery and placebo/supportive therapy after curative resection for operable hepatocellular carcinoma.
SEARCH STRATEGY
We searched The Cochrane Hepato-Biliary Group Controlled Trials Register, the Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library, MEDLINE, EMBASE, Science Citation Index Expanded, Chinese Biomedical Database, and US National Cancer Institute's Physician's Data Query Trials Database until 2005. References of the identified trials were also searched for identifying further trials.
SELECTION CRITERIA
Randomised and quasi-randomised trials that compared hepatocellular carcinoma patients who were given and not given neoadjuvant/adjuvant therapy as a supplement to curative liver resection.
DATA COLLECTION AND ANALYSIS
Data were extracted independently by two authors and discrepancies resolved by consensus. The survival and disease-free survival curves were compared using their one, two, three, four, and five-year survival rates, median survival times, and the result of the significance tests (P-values).
MAIN RESULTS
A total of 12 randomised trials were identified, totaling 843 patients. The size of the randomised clinical trials ranged from 30 to 155 patients. Both preoperative (neoadjuvant) and postoperative (adjuvant), systemic and locoregional (+/- embolisation), chemo- and immunotherapy interventions were tested. Treatment regimens and patients selected were not comparable, so no pooling was done. Only one regimen using preoperative transcatheter arterial chemoembolisation with doxorubicin was similar in two trials. Four of the twelve trials reported survival benefit at five years when given adjuvant or neoadjuvant therapy. Disease-free survival was reported in nine trials, and the estimated hazard ratios show that disease-free survival was significant in two trials at five years. These two trials had not shown a survival advantage, but the recurrence was significantly lower in patients given adjuvant or neoadjuvant therapy. The highest toxicity rate was in a trial using oral 1-hexylcarbamoyl 5-fluorouracil which resulted in 12 out of 38 patients being withdrawn from the trial because of adverse events.
AUTHORS' CONCLUSIONS
There is no clear evidence for efficacy of any of the adjuvant and neo-adjuvant protocols reviewed, but there is some evidence to suggest that adjuvant therapy may be beneficial offering prolonged disease-free survival. In order to detect a realistic treatment advantage, larger trials with lower risk of systematic error will have to be conducted.
Topics: Antineoplastic Agents; Carcinoma, Hepatocellular; Chemoembolization, Therapeutic; Chemotherapy, Adjuvant; Humans; Immunotherapy; Liver Neoplasms; Neoadjuvant Therapy; Randomized Controlled Trials as Topic
PubMed: 19160192
DOI: 10.1002/14651858.CD001199.pub2 -
Health Technology Assessment... Mar 2010To assess the clinical effectiveness and cost-effectiveness of topotecan as second-line treatment for small cell lung cancer (SCLC). (Review)
Review
OBJECTIVES
To assess the clinical effectiveness and cost-effectiveness of topotecan as second-line treatment for small cell lung cancer (SCLC).
DATA SOURCES
Bibliographic databases were searched from 1990 to February 2009, including the Cochrane library, MEDLINE (Ovid), EMBASE (Ovid), PREMEDLINE In-Process & Other Non-Indexed Citations. Bibliographies of related papers were assessed and experts were contacted to identify additional references and the manufacturer's submission to NICE was also searched.
REVIEW METHODS
Two reviewers independently screened titles and abstracts for eligibility. Inclusion criteria were applied to the full text of retrieved papers using a standard form. For the clinical effectiveness review, the studies were randomised controlled trials (RCTs), which included adult participants with relapsed SCLC who responded to first-line treatment and for whom re-treatment with first-line therapy was inappropriate. The treatment was topotecan (oral or intravenous, i.v.) compared with one another, best supportive care (BSC) or other chemotherapy regimens. Outcomes included measures of response or disease progression and measures of survival. For the cost-effectiveness review studies were eligible for inclusion if they reported cost-effectiveness, cost-utility, cost-benefit or cost-consequence analyses. Data extraction and quality assessment of included studies was undertaken by one reviewer and checked by a second. Studies were synthesised through a narrative review with full tabulation of results. An independent economic model estimated the cost-effectiveness of topotecan (oral or i.v.) compared with BSC. The model used survival analysis methods to derive estimates of mean survival for patients treated with topotecan or receiving BSC alone. These were combined with quality of life (QoL) weights to derive estimates of mean quality-adjusted life expectancy for patients receiving BSC alone or topotecan plus BSC. Categories of costs included in the model included drug use, chemotherapy administration and on-treatment monitoring, management of adverse events, monitoring for disease progression and palliative care.
RESULTS
A total of 434 references were identified of which five were included in the clinical effectiveness review. In these trials topotecan was compared with BSC, CAV [cyclophosphamide, Adriamycin (doxorubicin) and vincristine] or amrubicin, or oral topotecan was compared with i.v. topotecan. No economic evaluations were identified. There were no statistically significant differences between groups when i.v. topotecan was compared with either CAV or oral topotecan for overall response rate (ORR). Response rate was significantly better in participants receiving i.v. amrubicin than in those receiving a low dose of i.v. topotecan (38% versus 13%, respectively, p = 0.039). There was a statistically significant benefit in favour of oral topotecan compared with BSC (HR 0.61, 95% CI 0.43 to 0.87, p = 0.01). Drug acquisition costs for four cycles of treatment were estimated at 2550 pounds for oral topotecan and 5979 pounds for i.v. topotecan. Non-drug treatment costs accounted for an additional 1097 pounds for oral topotecan and 4289 pounds for i.v. topotecan. Total costs for the modelled time horizon of 5 years were 4854 pounds for BSC, 11,048 pounds for oral topotecan and between 16,914 pounds and 17,369 pounds for i.v. topotecan (depending on assumptions regarding time progression). Life expectancy was 0.4735, 0.7984 and 0.7784 years for BSC, oral topotecan and i.v. topotecan respectively. Total quality-adjusted life-years (QALYs) were 0.2247 and 0.4077, for BSC and oral topotecan respectively, resulting in an incremental cost-effectiveness ratio (ICER) of 33,851 pounds per QALY gained. Total QALYs for i.v. topotecan were between 0.3875 and 0.4157 (depending on assumptions regarding time progression) resulting in an ICER between 74,074 pounds and 65,507 pounds per QALY gained.
CONCLUSIONS
Topotecan appeared to be better than BSC alone in terms of improved survival, and was as effective as CAV and less favourable than i.v. amrubicin in terms of response. Oral topotecan and i.v. topotecan were similar in efficacy. Topotecan offers additional benefit over BSC, but at increased cost. ICERs for i.v. topotecan, compared with BSC, were high and suggest that it is unlikely to be a cost-effective option. The ICER for oral topotecan is at the upper extreme of the range conventionally regarded as cost-effective from an NHS decision-making perspective. Further research into the QoL of patients with relapsed SCLC could identify the impacts of disease progression and treatment response.
Topics: Adult; Antineoplastic Agents; Cost-Benefit Analysis; Humans; Lung Neoplasms; Small Cell Lung Carcinoma; Topotecan
PubMed: 20356561
DOI: 10.3310/hta14190 -
Metabolism: Clinical and Experimental Sep 2022Several anticancer agents have been associated with cardiac toxic effects. The currently proposed mechanisms to explain cardiotoxicity differ among anticancer agents,... (Review)
Review
Several anticancer agents have been associated with cardiac toxic effects. The currently proposed mechanisms to explain cardiotoxicity differ among anticancer agents, but in fact, the specific modulation is not completely elucidated. Thus, this systematic review aims to provide an integrative perspective of the molecular mechanisms underlying the toxicity of anticancer agents on heart muscle while using a high-throughput technology, mass spectrometry (MS)-based proteomics. A literature search using PubMed database led to the selection of 27 studies, of which 13 reported results exclusively on animal models, 13 on cardiomyocyte-derived cell lines and only one included both animal and a cardiomyocyte line. The reported anticancer agents were the proteasome inhibitor carfilzomib, the anthracyclines daunorubicin, doxorubicin, epirubicin and idarubicin, the antimicrotubule agent docetaxel, the alkylating agent melphalan, the anthracenedione mitoxantrone, the tyrosine kinase inhibitors (TKIs) erlotinib, lapatinib, sorafenib and sunitinib, and the monoclonal antibody trastuzumab. Regarding the MS-based proteomic approaches, electrophoretic separation using two-dimensional (2D) gels coupled with tandem MS (MS/MS) and liquid chromatography-MS/MS (LC-MS/MS) were the most common. Overall, the studies highlighted 1826 differentially expressed proteins across 116 biological processes. Most of them were grouped in larger processes and critically analyzed in the present review. The selection of studies using proteomics on heart muscle allowed to obtain information about the anticancer therapy-induced modulation of numerous proteins in this tissue and to establish connections that have been disregarded in other studies. This systematic review provides interesting points for a comprehensive understanding of the cellular cardiotoxicity mechanisms of different anticancer drugs.
Topics: Animals; Antineoplastic Agents; Cardiotoxicity; Chromatography, Liquid; Proteomics; Tandem Mass Spectrometry
PubMed: 35809654
DOI: 10.1016/j.metabol.2022.155250 -
Journal of Thoracic Oncology : Official... Apr 2007This clinical practice guideline, based on a systematic review, evaluates chemotherapy options for patients with relapsed small cell lung cancer (SCLC). (Meta-Analysis)
Meta-Analysis Review
PURPOSE
This clinical practice guideline, based on a systematic review, evaluates chemotherapy options for patients with relapsed small cell lung cancer (SCLC).
METHODS
Relevant randomized trials and meta-analyses were identified through a systematic search of the literature. External feedback was obtained from practitioners in Ontario, and the guideline was approved by the provincial lung cancer disease site group.
RESULTS
Six randomized trials met the eligibility criteria and were included for review. One randomized phase III trial of oral topotecan versus no treatment in patients receiving best supportive care found topotecan to have a significant benefit in terms of 6-month survival and quality of life. A randomized phase III trial compared outcomes of carboplatin in patients receiving a combination of etoposide and cisplatin (EP) and found no significant improvement associated with carboplatin, although it was associated with significantly higher grade 3/4 thrombocytopenia. Two randomized trials directly compared chemotherapy regimens (intravenous [i.v.] topotecan versus cyclophosphamide, doxorubicin, and vincristine (CAV); and bis-chloro-ethylnitrosourea, thiotepa, vincristine, and cyclophosphamide (BTOC) versus EP), but these trials found no significant differences in terms of disease response or survival. I.v. topotecan was associated with significantly higher toxicities (grade 4 thrombocytopenia and grade 3/4 anemia) and greater improvement in patient-reported symptoms compared with CAV. Two randomized trials of topotecan-treated patients comparing route of administration (i.v. versus oral) found no significant differences in terms of disease response, survival, or quality of life, although oral administration was associated with increased grade 3 or 4 diarrhea in both trials.
CONCLUSION
Evidence on the clinical benefit of second-line therapy in SCLC is limited. Topotecan is the most studied agent in this population; it has a response and survival benefit in comparison with placebo, but it also has greater toxicity in comparison with CAV. To date, significant differences in terms of response and survival are not evident in studied chemotherapy options.
Topics: Administration, Oral; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Small Cell; Clinical Trials, Phase III as Topic; Etoposide; Female; Humans; Infusions, Intravenous; Lomustine; Lung Neoplasms; Male; Maximum Tolerated Dose; Melphalan; Middle Aged; Neoplasm Recurrence, Local; Neoplasm Staging; Ontario; Practice Guidelines as Topic; Prognosis; Randomized Controlled Trials as Topic; Salvage Therapy; Survival Analysis; Topotecan
PubMed: 17409809
DOI: 10.1097/01.JTO.0000263720.15062.51 -
The Cochrane Database of Systematic... May 2014Approximately 13% of women diagnosed with endometrial cancer present with advanced stage disease (International Federation of Gynecology and Obstetrics (FIGO) stage... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Approximately 13% of women diagnosed with endometrial cancer present with advanced stage disease (International Federation of Gynecology and Obstetrics (FIGO) stage III/IV). The standard treatment of advanced endometrial cancer consists of cytoreductive surgery followed by radiation therapy, or chemotherapy, or both. There is currently little agreement about which adjuvant treatment is the safest and most effective.
OBJECTIVES
To evaluate the effectiveness and safety of adjuvant chemotherapy compared with radiotherapy or chemoradiation, and to determine which chemotherapy agents are most effective in women presenting with advanced endometrial cancer (FIGO stage III/IV).
SEARCH METHODS
We searched the Cochrane Gynaecological Cancer Collaborative Review Group's Trial Register, the Cochrane Central Register of Controlled Trials (CENTRAL) (Issue 10 2013), MEDLINE and EMBASE up to November 2013. Also we searched electronic clinical trial registries for ongoing trials.
SELECTION CRITERIA
Randomised controlled trials (RCTs) of adjuvant chemotherapy compared with radiotherapy or chemoradiation in women with FIGO stage III and IV endometrial cancer.
DATA COLLECTION AND ANALYSIS
Two review authors selected trials, extracted data, and assessed trials for risk of bias. Where necessary, we contacted trial investigators for relevant, unpublished data. We pooled data using the random-effects model in Review Manager (RevMan) software.
MAIN RESULTS
We included four multicentre RCTs involving 1269 women with primary FIGO stage III/IV endometrial cancer. We considered the trials to be at low to moderate risk of bias. All participants received primary cytoreductive surgery. Two trials, evaluating 620 women (83% stage III, 17% stage IV), compared adjuvant chemotherapy with adjuvant radiotherapy; one trial evaluating 552 women (88% stage III, 12% stage IV) compared two chemotherapy regimens (cisplatin/doxorubicin/paclitaxel (CDP) versus cisplatin/doxorubicin (CD) treatment) in women who had all undergone adjuvant radiotherapy; and one trial contributed no data.Overall survival (OS) and progression-free survival (PFS) was longer with adjuvant chemotherapy compared with adjuvant radiotherapy (OS: hazard ratio (HR) 0.75, 95% confidence interval (CI) 0.57 to 0.99, I² = 22%; and PFS: HR 0.74, 95% CI 0.59 to 0.92, I² = 0%). Sensitivity analysis using adjusted and unadjusted OS data, gave similar results. In subgroup analyses, the effects on survival in favour of chemotherapy were not different for stage III and IV, or stage IIIA and IIIC (tests for subgroup differences were not significant and I² = 0%). This evidence was of moderate quality. Data from one trial showed that women receiving adjuvant chemotherapy were more likely to experience haematological and neurological adverse events and alopecia, and more likely to discontinue treatment (33/194 versus 6/202; RR 5.73, 95% CI 2.45 to 13.36), than those receiving adjuvant radiotherapy. There was no statistically significant difference in treatment-related deaths between the chemotherapy and radiotherapy treatment arms (8/309 versus 5/311; Risk Ratio (RR) 1.67, 95% CI 0.55 to 5.00).There was no clear difference in PFS between intervention groups in the one trial that compared CDP versus CD (552 women; HR 0.90, 95% CI 0.69 to 1.17). We considered this evidence to be of moderate quality. Mature OS data from this trial were not yet available. Severe haematological and neurological adverse events occurred more frequently with CDP than CD.We found no trials to include of adjuvant chemotherapy versus chemoradiation in advanced endometrial cancer; however we identified one ongoing trial of this comparison.
AUTHORS' CONCLUSIONS
There is moderate quality evidence that chemotherapy increases survival time after primary surgery by approximately 25% relative to radiotherapy in stage III and IV endometrial cancer. There is limited evidence that it is associated with more adverse effects. There is some uncertainty as to whether triplet regimens offer similar survival benefits over doublet regimens in the long-term. Further research is needed to determine which chemotherapy regimen(s) are the most effective and least toxic, and whether the addition of radiotherapy further improves outcomes. A large trial evaluating the benefits and risks of adjuvant chemoradiation versus chemotherapy in advanced endometrial cancer is ongoing.
Topics: Antineoplastic Combined Chemotherapy Protocols; Chemoradiotherapy; Chemotherapy, Adjuvant; Cisplatin; Disease-Free Survival; Doxorubicin; Endometrial Neoplasms; Female; Humans; Neoplasm Staging; Paclitaxel; Radiotherapy, Adjuvant; Randomized Controlled Trials as Topic
PubMed: 24832785
DOI: 10.1002/14651858.CD010681.pub2