Growth modulation index as metric of clinical benefit assessment among advanced soft tissue sarcoma patients receiving trabectedin as a salvage therapy.

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.

Is erectile dysfunction a sentinel symptom for cardiovascular autonomic neuropathy in patients with type 2 diabetes?

The study investigated whether there is a significant association between erectile dysfunction (ED) secondary to autonomic failure, and cardiovascular autonomic neuropathy (CAN) in male patients suffering from type 2 diabetes. Twenty-two patients suffering from type 2 diabetes were recruited for this study after satisfying the stringent exclusion criteria used in the first stage. They had no evidence of overt cardiovascular disease, hypertension, neurological, renal or thyroid disease. Each subject was assessed for ED and CAN using standardized tests. Six patients were suffering from CAN while 10 patients were suffering from ED. There was no significant association between CAN and autonomic ED (P = 1). Three patients with normal erectile function had CAN, whilst three patients with ED had CAN. Further analysis demonstrates a significant increase in association between ED and CAN with age (P = 0.036). These results show that ED secondary to autonomic neuropathy is not significantly associated with CAN in this specific group of patients. Nonetheless, the study reveals that ED is a sentinel symptom for future development of CAN.