Adjuvant chemotherapy for soft-tissue sarcoma: review and meta-analysis of the published results of randomised clinical trials

Abstract

(Pinedo and Verweij, 1986). Approximately 90% of all STS patients present with apparently localised masses and no clinical evidence of metastasis (Rosenberg et al., 1983). Where anatomically possible, initial treatment usually involves radical surgery (Souhami, 1986), although good control of the primary tumour can also be achieved by conservative surgery in conjunction with radiotherapy (Mazanet and Antman, 1991). Despite good local control, around 50% of patients with high-grade tumours will die from metastatic disease (Delaney et al., 1991). Thus, there has been interest in the potential of adjuvant chemotherapy to control micrometastases and improve survival.A number of randomised clinical trials have compared local surgical treatment (with or without radiotherapy) followed by adjuvant chemotherapy with local treatment alone. As in many other areas of cancer research, these trials have not been large enough to demonstrate moderate treatment effects with reliability. Almost all have involved fewer than 250 patients, although one trial conducted by the European Organization for Research and Treatment into Cancer has recruited 468 patients (Bramwell et al., 1994). Thus, these trials are unlikely to produce conventionally significant results, and could easily be interpreted as 'negative trials'. A more appropriate interpretation would be to consider them as being inconclusive trials.Although individual trials may have insufficient numbers of patients to detect moderate survival benefits, 'combining' the results of these trials might indicate whether adjuvant chemotherapy is likely to be beneficial in the treatment of STS. This paper therefore reviews qualitatively, then quantitatively, the results of all published randomised trials of adjuvant chemotherapy in STS. Materials and methodsPublished randomised trials of chemotherapy in STS were identified using the Medline and Cancerlit databases and by examining the reference lists of already identified trials, review articles and books. Of 20 potentially eligible trials, four were excluded because they were non-adjuvant trials that randomised patients with advanced disease only (Schoenfeld et al., 1982;Pinedo et al., 1984;Baker et al., 1987;Borden et al., 1990) and one because all patients received induction chemotherapy before randomisation (Eilber et al., 1988). Relevant details and results were extracted from most recent publications of the 15 remaining trials and collated to form the basis of the qualitative review and meta-analysis.For the meta-analysis, 2 year and 5 year survival rates were taken from the most recent publication for each trial (except in one instance where they were taken from an earlier publication) and analysed using the methods described below (Stewart, 1992). If the 2 year and 5 year survival figures were not quoted, they were estimated from the published survival curves and the numbers at risk reduced, where appropriate, to allow for immature follow-up (Stewart and Parmar, 1993). This technique, which assumes proportional hazards, stand...

Racial and ethnic differences in treatment and survival among adults with primary extremity soft‐tissue sarcoma

“…Data on whether adjuvant chemotherapy improves survival in patients with ESTS are conflicting. [33][34][35] Therefore, it is unlikely that the use of or the failure to use systemic chemotherapy was responsible for any of the survival differences observed in our study. We attempted to control for potential confounding factors that could influence our ability to detect differences between racial or ethnic groups, but this admittedly is hard to do.…”

Prognostic factors in soft-tissue sarcomas: what have we learnt?

“…An early meta-analysis had suggested that the addition of adjuvant chemotherapy had a beneficial effect on overall survival [17]; but it was not till a quantitative meta-analysis of updated data from individual patients from all available randomized trials was performed that evidence was put forward which showed a statistically significant improvement in local and distant recurrence-free survival and overall recurrencefree survival [18]. Disappointingly, despite the inclusion of 14 trials with 1568 patients, this meta-analysis was unable to demonstrate more than a trend for improved overall survival.…”

Chemotherapy for adult soft tissue sarcoma

“…However, problems in a majority of the studies were their small size, patient heterogeneity as regards histological types, tumour localisation and malignancy grade, and inadequacy of the chemotherapy regimens. Recently, a metaanalysis of the studies ( 1 ,546 patients) was performed, and although one was able to fmd a small but significant survival benefit for chemotherapy-treated patients, it was concluded that the approximations that were necessary to merge the hererogenous materials were methodologically unacceptable, and a re-analysis based on individual patient data had to be undertaken [30]. It must be concluded that as of today, adjuvant chemotherapy has no established place in the treatment of adult soft tissue sarcoma, and no subgroup of patients has so far been identified that has a reproducible advantage from such treatment.…”

“…50% of patients with ASTS, and multiple attempts have been made to use adjuvant chemotherapy to combat micrometastatic disease at an early stage. To date, 15 prospective randomized studies have been performed, of which seven employed single agent doxorubicin and eight employed combination chemotherapy [19,[28][29][30]. Only two small studies have been able to show significant differences in both metastasis-free and overall survival in favour of the chemotherapy arm.…”