Reichle Albrecht, Vogt Thomas, Coras Brigitte, Terheyden Peter, Neuber Klaus, Trefzer Uwe, Schultz Erwin, Berand Anna, Bröcker E B, Landthaler Michael, Andreesen Reinhard
Department of Hematology/Oncology, University Hospital Regensburg, Regensburg, Germany.
Melanoma Res. 2007 Dec;17(6):360-4. doi: 10.1097/CMR.0b013e3282f1d2c8.
An angiostatic approach was used to assess the impact of anti-inflammatory therapy in combination with metronomic low-dose chemotherapy. A randomized multi-institutional phase II trial was designed to select metronomic chemotherapy (arm A: trofosfamide 50 mg orally three times daily, day 1+) or combined anti-inflammatory/angiostatic treatment (arm B: trofosfamide as above mentioned plus rofecoxib 25 mg orally, day 1+, and pioglitazone 60 mg orally, day 1+) for further evaluation. A total of 76 patients, mostly (>60%) refractory to at least one previous chemotherapy with maximum tolerated doses, and progression of metastatic melanoma were included. The estimated progression-free survival (PFS) rates at one year were 0% for metronomic chemotherapy (A), but 9% for additional anti-inflammatory therapy (B). Vice versa the hazard ratio for the intent-to-treat analysis of A versus B was 1.9 (P=0.008). By Cox analysis, the impact of anti-inflammatory therapy on PFS achieved significance (P=0.016) as well as C-reactive protein response on overall survival (P=0.045). WHO grade 3 (no grade 4) toxicities were reported in arm A/B in 19 and 28%, respectively. In conclusion, control of tumour-associated inflammatory processes (C-reactive protein response) is associated with longer PFS than achieved with metronomic chemotherapy alone in metastatic melanoma.
采用血管生成抑制方法评估抗炎治疗联合节拍性低剂量化疗的效果。设计了一项随机多机构II期试验，以选择节拍性化疗（A组：曲磷胺50毫克，口服，每日三次，第1天起）或联合抗炎/血管生成抑制治疗（B组：上述曲磷胺加罗非昔布25毫克，口服，第1天起，以及吡格列酮60毫克，口服，第1天起）进行进一步评估。共纳入76例患者，大多数（>60%）对至少一种先前的最大耐受剂量化疗难治，且患有转移性黑色素瘤并出现进展。节拍性化疗（A组）一年的无进展生存（PFS）率估计为0%，但联合抗炎治疗（B组）为9%。反之，A组与B组意向性治疗分析的风险比为1.9（P = 0.008）。通过Cox分析，抗炎治疗对PFS的影响具有显著性（P = 0.016），C反应蛋白反应对总生存的影响也具有显著性（P = 0.045）。A组和B组分别有19%和28%报告出现WHO 3级（无4级）毒性反应。总之，在转移性黑色素瘤中，控制肿瘤相关炎症过程（C反应蛋白反应）与比单独使用节拍性化疗更长的PFS相关。
