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Database of Abstracts of Reviews of Effects (DARE): Quality-assessed Reviews [Internet].

Effectiveness and safety of oxaliplatin compared to cisplatin for advanced, unresectable gastric cancer: a systematic review and meta-analysis

F Montagnani, G Turrisi, C Marinozzi, C Aliberti, and G Fiorentini.

Review published: 2011.

CRD summary

The review found that for treating advanced unresectable oesophagogastric cancer, oxaliplatin was associated with a small but significant advantage over cisplatin for overall and progression-free survival, and was less toxic and more tolerable. The authors' conclusions may require cautious interpretation given poor reporting of review methods and the inclusion of only three trials, only one of which was large.

Authors' objectives

To compare the effectiveness and safety of oxaliplatin to cisplatin for advanced unresectable gastric cancer.

Searching

PubMed, CANCERLIT, EMBASE and Cochrane Central Register of Controlled Trials (CENTRAL) were searched. Search terms were reported. Posters from the annual meetings of the European and American Societies of Medical Oncology were checked for the previous 10 years.

Study selection

Randomised controlled trials (RCTs) that compared the effectiveness and safety of oxaliplatin to cisplatin for treating advanced unresectable oesophagogastric cancer were eligible for inclusion.

Participants in the included trials had unresectable locally advanced or metastatic gastric or gastro-oesophageal junction adenocarcinoma. Participant characteristics were well balanced between the groups. Included interventions were oxaliplatin (85mgs/m2) versus cisplatin (50mgs/m2) given for the first two days of each 14 or 21 day cycle, in combination with epirubicin, capecitabine, 5-fluorouracil and/or folinic acid (in both trial arms). Outcomes reported in the review were death, disease progression, response, all-grade and high-grade (grade 3-4) adverse events, and overall compliance and tolerability.

The authors did not state how many reviewers performed study selection.

Assessment of study quality

Trial quality was evaluated using the Jadad scale, which assessed the adequacy of reported randomisation, double blinding, and withdrawals or drop-outs. Each trial was awarded a score out of a maximum of 5 points.

The authors did not state how the assessment was performed.

Data extraction

Odds ratios (ORs) were extracted or calculated for dichotomous outcomes and hazard ratios (HRs) for death or progression, with 95% confidence intervals (CIs). An intention to treat approach was used. Trials which allowed crossover between the arms were not included in the survival analysis.

Two reviewers independently extracted the data, with disagreements resolved by a third reviewer.

Methods of synthesis

Hazard ratios were combined using inverse logarithmic conversion to calculate pooled hazard ratios and 95% confidence intervals for survival outcomes. Pooled odds ratios and 95% confidence intervals were also calculated. Heterogeneity was assessed using the Q test and I2, using a fixed-effect Mantel-Haenszel model.

Sensitivity analyses were conducted to examine the effects of excluding one trial, of using alternative meta-analysis software and of using a random-effects model.

There were too few trials to assess publication bias.

Results of the review

One phase III RCT and two phase II RCTs were included in the review (n=1,294 patients in text, 1284 in table 1; range 62 to 1,002). One RCT scored 3 on the Jadad scale and two RCTs scored 2.

Effectiveness: When the three RCTs were combined, oxaliplatin was associated with a significantly lower risk of death (HR 0.88, 95% CI 0.78 to 0.99) and cancer progression (HR 0.88, 95% CI 0.80 to 0.98). The absolute benefit represented a risk reduction of 12% for death and progression. There was no significant difference between the treatment groups for response rates.

Safety: When the three RCTs were pooled, oxaliplatin was associated with a significantly lower risk of high-grade neutropenia (OR 0.53, 95% CI 0.41 to 0.69), high-grade anaemia (OR 0.64, 95% CI 0.41 to 0.98), alopecia (OR 0.56, 95% CI 0.41 to 0.74) and thromboembolism (OR 0.42, 95% CI 0.28 to 0.64). However, oxaliplatin was associated a significantly higher risk of high-grade diarrhoea (OR 2.73, 95% CI 1.66 to 4.49) and high-grade neurotoxicity (OR 6.91, 95% CI 3.08 to 15.46). Rates of thrombocytopenia, nausea/vomiting and stomatitis did not differ significantly between the treatment groups. One RCT (n=220) reported that bi-weekly two-drug oxaliplatin was associated with significantly higher compliance and tolerability than cisplatin, especially in older participants (aged over 65 years).

Results for all-grade toxicity and sensitivity analyses were also reported.

There was no significant heterogeneity for most outcome except all-grade diarrhoea (p<0.01).

Authors' conclusions

For treating advanced unresectable oesophagogastric cancer, oxaliplatin was associated with a small but significant benefit in overall and progression-free survival compared with cisplatin. Oxaliplatin was also less toxic and more tolerable than cisplatin, with the exception of diarrhoea.

CRD commentary

The objectives and inclusion criteria of the review were clear. Relevant sources were searched for studies, apparently without restriction by publication status. It was unclear whether there was a language restriction and search dates were not reported. Steps were taken to minimise the risk of reviewer bias and error, with one reviewer independently extracting the data, but it was unclear whether these precautions also applied to study selection and quality assessment.

Some relevant aspects of trial quality were evaluated, but no details were reported on some important characteristics of individual trials (such as allocation concealment, follow-up rates and duration of follow-up). This made it difficult to assess the reliability and applicability of the overall findings. Appropriate statistical techniques were used to combine the trials and to assess and investigate heterogeneity between them. As the authors noted, the review was limited by the small number of trials available (with one trial including most of the participants), the lack of information on second-line treatment, and the possibility (which could not be assessed) of publication bias.

The authors' conclusions may require cautious interpretation, due to poor reporting of review methods and the inclusion of only three trials, only one of which was large.

Implications of the review for practice and research

Practice: The authors stated that oxaliplatin was associated with less toxicity and better tolerability than cisplatin, especially in older patients and when used in two drug bi-weekly regimens.

Research: The authors stated that future studies of advanced gastric cancer should investigate treatment regimens combining chemotherapeutic agents and newer biological agents (such as tyrosine kinase inhibitors and monoclonal antibodies).

Funding

Azienda Unita Sanitaria Locale 11 (AUSL 11), Italy.

Bibliographic details

Montagnani F, Turrisi G, Marinozzi C, Aliberti C, Fiorentini G. Effectiveness and safety of oxaliplatin compared to cisplatin for advanced, unresectable gastric cancer: a systematic review and meta-analysis. Gastric Cancer 2011; 14(1): 50-55. [PubMed: 21340667]

PubMedID

21340667

Indexing Status

Subject indexing assigned by NLM

MeSH

Cisplatin /adverse effects /therapeutic use; Disease Progression; Esophageal Neoplasms /drug therapy; Humans; Organoplatinum Compounds /adverse effects /therapeutic use; Stomach Neoplasms /drug therapy; Treatment Outcome

AccessionNumber

12011002528

Date bibliographic record published

07/09/2011

Date abstract record published

01/02/2012

Record Status

This is a critical abstract of a systematic review that meets the criteria for inclusion on DARE. Each critical abstract contains a brief summary of the review methods, results and conclusions followed by a detailed critical assessment on the reliability of the review and the conclusions drawn.

CRD has determined that this article meets the DARE scientific quality criteria for a systematic review.

Copyright © 2014 University of York.

PMID: 21340667

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