ABSTRACT
BACKGROUND: The growth modulation index (GMI) is the ratio of time to progression with the nth line (TTP(n)) of therapy to the TTP(n)(-1) with the n-1th line. GMI >1.33 is considered as a sign of activity in phase II trials. PATIENTS AND METHODS: This retrospective analysis evaluated the concordance between the GMI and the efficacy outcomes in 279 patients with advanced soft tissue sarcoma (ASTS) treated with trabectedin 1.5 mg/m² (24-h infusion every 3 weeks) in four phase II trials. RESULTS: One hundred and forty-two (51%) patients received one prior line and 137 ≥ 2 lines. The median TTP(n) was 2.8 months (range 0.2-26.8), whereas the median TTP(n)(-1) was 4.0 months (0.3-79.5). The median GMI was 0.6 (0.0-14.4). Overall, 177 patients (63%) had a GMI <1; 21 (8%) a GMI equal to 1-1.33 and 81 (29%) a GMI >1.33, which correlated with the median overall survival in those patients (9.1, 13.9 and 23.8 months, respectively, P = 0.0005). A high concordance rate between the GMI and response rate (P < 0.0001) and progression-free survival (PFS, P < 0.0001) was observed. Good performance status (PS) was the only factor associated with GMI >1.33 (PS = 0; P < 0.04). CONCLUSIONS: A high GMI was associated with favorable efficacy outcomes in patients treated with trabectedin. Further research is needed to assess GMI as an indicator in this setting.
Subject(s)
Antineoplastic Agents, Alkylating/therapeutic use , Cell Proliferation/drug effects , Dioxoles/therapeutic use , Sarcoma/drug therapy , Tetrahydroisoquinolines/therapeutic use , Adult , Aged , Aged, 80 and over , Antibiotics, Antineoplastic/therapeutic use , Disease-Free Survival , Doxorubicin/therapeutic use , Female , Humans , Male , Middle Aged , Retrospective Studies , Salvage Therapy , Sarcoma/metabolism , Sarcoma/mortality , Sarcoma/pathology , Trabectedin , Treatment Outcome , Young AdultABSTRACT
The EORTC Soft Tissue and Bone Sarcoma Group has conducted a phase II trial in 33 eligible patients with metastatic soft tissue sarcoma with nimustine 100 mg/m2 every 6 weeks. In 31 evaluable patients there were 3 (10%) partial responses lasting 4.5, 6 and 7.5 months, and 5 cases of stable disease. 12 patients had progressive disease and 11 patients early progressive disease. Toxicity consisted mainly of leukopenia and thrombocytopenia and nausea and vomiting. It is concluded that nimustine has only minor activity in soft tissue sarcoma.
