CRD summary

This review concluded that there was no definitive evidence to suggest that any one chemotherapy regimen prolonged survival in patients with cancer of unknown primary site. The authors' conclusions appeared cautious, but limitations with the included studies and a lack of reporting in the review made it difficult to determine their reliability.

Authors' objectives

To assess the effectiveness of chemotherapy regimens on survival in patients with cancer of unknown primary site.

Searching

PubMed and Cochrane Central Registry of Controlled Trials (CENTRAL) were searched for relevant articles in any language. PubMed was cross-referenced using the names of lead authors in eligible trials. The last search update was performed in March 2009; it was unclear from which date searches began. Search terms were reported. References of retrieved articles were searched manually.

Study selection

Randomised controlled trials (RCTs) that compared at least two arms of different chemotherapy regimens (different agents or schedules) or a chemotherapy regimen with a control (best supportive care) in patients with cancer of unknown primary site (unfavourable subset) were eligible for inclusion. The outcome of interest was death. Eligible studies could include treatment with radiotherapy, hormonal and gene therapy if these regimens were the same in all compared arms and the difference referred to the chemotherapy regimen only.

Included studies were published between 1980 and 2009. No studies that compared chemotherapy with best supportive care were found. Included studies used 16 different treatments administered in different combinations. Patients varied in terms of performance status 2 or worse (Karnofsky score 70 or worse).

The authors did not state how many reviewers selected studies for inclusion.

Assessment of study quality

The authors did not state that they assessed validity.

Data extraction

Three reviewers extracted data on median survival rates and the number of deaths per treatment arm. Discrepancies were resolved by consensus. Where studies included more than two treatment arms, each pair of a comparison was assessed separately. Hazard ratios (HRs) and their 95% confidence intervals (CIs) were extracted where reported. Where HRs were not reported, study authors were contacted for data; where such data were not available, HRs and their 95% CIs were imputed from the number of events and patients in each treatment arm.

Methods of synthesis

A random-effects model was used to combine HRs for each direct treatment comparison. Statistical heterogeneity was assessed using the I² statistic.

A hierarchical Bayesian model was used to combine HRs and their credibility intervals (Crls) from both direct and indirect comparisons (multiple-treatments meta-analysis). Studies were grouped by regimen: platinum without taxane; platinum plus taxane; taxane without platinum; non-platinum, non-taxane monotherapy; and non-platinum, non-taxane combination. Treatment regimens were ranked by effectiveness in prolonging survival.

Results of the review

Ten RCTs (n=683) were included in the review and eight RCTs (n=543) were included in the multiple-treatments meta-analysis. Sample sizes ranged from 34 to 101 patients (median 73, interquartile range 49 to 87).

Median survival ranged between 1.6 and 13.6 months. One trial (n=84) showed a statistically significant difference in survival and favoured combination therapy (cisplatin, epirubicin, mitomycin-C) with a median survival of 9.4 months compared with monotherapy (mitomycin-C) with a median survival of 5.4 months (p<0.05). No other comparisons were significantly different.

Multiple-treatments meta-analysis showed no significant differences between different treatment regimens. Treatment regimen rankings were reported in the review.

Authors' conclusions

There was no definitive evidence to conclude that one type of chemotherapy regimen prolonged survival in patients with cancer of unknown primary site.

CRD commentary

The review question was clear and was supported by appropriate inclusion criteria. The literature search included two electronic databases and one other appropriate source. There were no language restrictions. No searches for unpublished data were undertaken and potentially relevant papers may have been missed. Validity was not assessed, which may have impacted on the robustness of subsequent conclusions. Data were extracted in duplicate; it was unclear whether this was true for study selection and so reviewer error and bias could not be ruled out. The authors attempted to include all available evidence in a multiple-treatments meta-analysis, but as statistical heterogeneity was not reported and study characteristics (such as treatment dose and schedule, additional treatments) and patient characteristics were limited, it was difficult to determine whether pooling of the results was appropriate. Credibility intervals were wide and the authors acknowledged certain limitations with this. Although the authors' conclusions appeared appropriately cautious, given the limitations with the included studies, small sample sizes and a lack of reporting in the review, the conclusions should be interpreted with caution and it is difficult to determine how reliable they are.

Implications of the review for practice and research

Practice: The authors did not state any implications for practice.

Research: The authors stated that further research on use of platinum and/or taxane regimens was required.

Funding

None.

Bibliographic details

Golfinopoulos V, Pentheroudakis G, Salanti G, Nearchou AD, Ioannidis JP, Pavlidis N. Comparative survival with diverse chemotherapy regimens for cancer of unknown primary site: multiple-treatments meta-analysis. Cancer Treatment Reviews 2009; 35(7): 570-573. [PubMed: 19539430]

Original Paper URL

http://www.cancertreatmentreviews.com/article/PIIS0305737209000875/abstract

Indexing Status

Subject indexing assigned by NLM

MeSH

Antineoplastic Combined Chemotherapy Protocols /therapeutic use; Humans; Neoplasms, Unknown Primary /drug therapy; Randomized Controlled Trials as Topic; Survival Analysis

AccessionNumber

12010000027

Database entry date

24/03/2010

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.