Alveolar Soft Part Sarcoma: Should We Be Targeting the Tumor or Targeting the Vasculature?

rent series. On the other hand 1 or 2 of the patients had not been pretreated with chemotherapy. This aspect can be of influence since there are data to suggest differences in the outcome of trabectedin treatment, depending on the level of pretreatment with cytotoxics [8]. However, all of these are minor issues to put the observations into context. The most important issue is the absence of formal response evaluation criteria in solid tumors (RECIST)based tumor regressions in the patients treated. This renders it important to try and assess the relevance of stable disease (SD). Acknowledging the potential relevance of SD in patients with soft tissue sarcomas the European Organization for Treatment and Research of Cancer (EORTC) Soft Tissue and Bone Sarcoma Group has propagated the use of progression free rates (PFR) as a tool for clinical trial purposes in screening studies to assess the potential activity of the drug under study [10]. The 6-month PFR of 57% reported by Pink et al. [9] is clearly higher than the 40% 6-month PFR indicated by the EORTC to suggest an agent may be active. However, ASPS patients were not included in the EORTC studies that were used to create the reference. Due to the indolent behavior of this subtype it is quite likely that the PFR boundaries indicated by the EORTC cannot be applied to ASPS, since they would lead to overestimation of actual drug activity. So how can we be sure that the suggested activity is relevant? The other way to assess this would be by use of the growth modulation index (GMI) [11], as the investigators have done, comparing the time to progression (TTP) on the current treatment to the TTP on the previous treatment. This can only be done in patients that have been pretreated. In this respect there seems to be a possible inconsistency in the paper concerning patient F that in table 1 is listed as pretreated and in table 2 as non-pretreated. If the latter where correct, the GMI cannot be calculated and thus not reported in table 3 for patient F. However, even when excluding this patient, in all pretreated patients the GMI this seems to favor the trabectedin use. Again, a word of caution is indicated, since one has to realize the data on TTP on the prior therapy, due to the retroSoft tissue sarcomas constitute a heterogeneous group of tumors that, due to their rare occurrence, used to be pooled for treatment assessment purposes. With the improvement in diagnostics and the development of molecularly targeted agents one has become increasingly aware that it is important, however, to differentiate the various subtypes from one another [1]. The development of imatinib for gastrointestinal stromal tumors (GIST) [2] can serve as an example. Alveolar soft part sarcoma (ASPS) is an extremely rare subtype of soft tissue sarcoma. It is characterized by translocation der(17) t(X:17)(p11;p25) on one hand, and a usually indolent growth pattern on the other [3]. Similar to GIST, it is quite insensitive to the commonly used cytotoxic drugs [4]. Trabectedin (ET-743; Yondelis, PharmaMar SA, Madrid, Spain), an agent isolated from the Caribbean tunicate Ecteinascidia turbinata. Trabectedin is a cytotoxic drug that binds to the minor groove of DNA [5], and induces double-stranded DNA breaks [6] and aG2-M cell cycle arrest [7]. Trabectedin is registered for use in soft tissue sarcomas in the EU and several other countries. While in general the response rates observed with its use are low, the level of progression arrest achieved is considerable [8]. However, studies on the activity of the agent in ASPS are lacking. In this issue of Onkologie, Pink et al. [9] present a retrospective analysis on a collected case series of 7 patients with ASPS treated with trabectedin. The retrospective collection and analysis of the series is hampered by the inevitable limitations of each retrospective analysis, for instance the impossibility to exclude an unintended patient selection bias. This in itself calls for major caution in trying to interpret the data of any case report based series. Five of the 7 patients were treated with the registered dose for trabectedin, which is 1.5 mg/m as a 24-h continuous intravenous infusion, repeated every 21 days. 2 patients were given a reduced dose. A clear dose-response relationship for trabectedin in soft tissue sarcoma has not been described yet, but if there is one, it is unlikely this will have negatively influenced the outcome interpretation of the treatment in the cur-