Semiglazov V F, Stepula V V, Dudov A, Schnitker J, Mengs U
Petrov Research Institute of Oncology, St. Petersburg, Russia.
Anticancer Res. 2006 Mar-Apr;26(2B):1519-29.
The objective of this randomised, multicentre, double-blind clinical trial was to investigate the impact of PS76A2, an aqueous mistletoe extract standardised to mistletoe lectins, on quality of life (QoL) in breast cancer patients. A total of 352 patients were randomly allocated to 2 groups receiving PS76A2 (15 ng mistletoe lectin/0.5 ml) or matching placebo twice weekly for 4 to 6 cycles of CMF (cyclophosphamide, methotrexate, fluorouracil) chemotherapy followed by 2 months follow-up. The primary efficacy end-point was the change from baseline of 3 FACT-G subscales (physical, emotional and functional well-being) during the fourth CMF cycle. Secondary measures included GLQ-8 (8 linear analogue self-assessment scales), Spitzer's uniscale and haematological variables. The main variables of safety analysis were adverse events, including injection site reactions and clinical laboratory tests. The results showed that physical, emotional and functional well-being improved upon PS76A2, but deteriorated following placebo. The treatment differences were statistically significant for the 3 subscales as well as for the summary score FACT-G, which was analysed as O'Brien's rank sum of its 3 subscales: The total score increased by 4.40 +/- 11.28, indicating a higher QoL after PS76A2, but decreased by 5.11 +/- 11.77 with placebo (p<0.0001). The GLQ-8 sum of 8 LASA scales was analysed as a summary score of GLQ-5 (sum of item nos. 1, 5, 6, 7, 8) and GLQ-3 (sum of item nos. 2, 3, 4). GLQ-5 characterises typical aspects of QoL, while GLQ-3 consists of 3 side-effects of CMF (feeling sick, numbness or pins and needles, loss of hair). GLQ-5 decreased by 42.9 +/- 125.0 upon PS76A2, indicating an improvement in QoL, but increased by 60.3 +/- 94.0 upon placebo (p<0.0001). GLQ-3 deteriorated in both groups (PS76A2: 13.9 +/- 52.4; placebo: 34.5 +/- 57.0), but the differences in favour of PS76A2 were, nevertheless, statistically significant (p=0.0007). The total score GLQ-8 improved by 28.9 +/- 154.6 after PS76A2 and deteriorated by 94.8 +/- 141.1 after placebo (p<0.0001). Spitzer's uniscale improved by 12.2 +/- 30.7 upon PS76A2 and deteriorated by 10.8 +/- 26.1 with placebo (p<0.0001). After follow-up without chemotherapy, a significant treatment difference in favour of PS76A2 was determined by means of FACT-G, GLQ-8 and Spitzer's uniscale. PS76A2 was well tolerated in this trial, with the exception of slight local reactions in 17.6% of the PS76A2 group. In conclusion, PS76A2 (15 ng mistletoe lectin/0.5 ml twice weekly) was shown to be safe and effective in improving QoL in breast cancer patients during chemotherapy and follow-up.
这项随机、多中心、双盲临床试验的目的是研究PS76A2（一种标准化为槲寄生凝集素的槲寄生水提取物）对乳腺癌患者生活质量（QoL）的影响。总共352名患者被随机分为两组，一组接受PS76A2（15 ng槲寄生凝集素/0.5 ml），另一组接受匹配的安慰剂，每周两次，共进行4至6个周期的CMF（环磷酰胺、甲氨蝶呤、氟尿嘧啶）化疗，随后进行2个月的随访。主要疗效终点是第四个CMF周期中3个FACT - G子量表（身体、情感和功能健康）相对于基线的变化。次要测量指标包括GLQ - 8（8个线性模拟自评量表）、斯皮策单分量表和血液学变量。安全性分析的主要变量是不良事件，包括注射部位反应和临床实验室检查。结果显示，PS76A2治疗后身体、情感和功能健康状况有所改善，而安慰剂治疗后则恶化。3个子量表以及FACT - G总结评分的治疗差异具有统计学意义，FACT - G总结评分是将其3个子量表作为奥布赖恩秩和进行分析的：总分增加了4.40±11.28，表明PS76A2治疗后生活质量更高，而安慰剂治疗后降低了5.11±11.77（p<0.0001）。GLQ - 8的8个LASA量表总和被分析为GLQ - 5（项目编号1、5、6、7、8的总和）和GLQ - 3（项目编号2、3、4的总和）的总结评分。GLQ - 5表征生活质量的典型方面，而GLQ - 3由CMF的3种副作用组成（感到恶心、麻木或刺痛、脱发）。PS76A2治疗后GLQ - 5降低了42.9±125.0，表明生活质量有所改善，而安慰剂治疗后增加了60.3±94.0（p<0.0001）。两组中GLQ - 3均恶化（PS76A2组：13.9±52.4；安慰剂组：34.5±57.0），但有利于PS76A2的差异仍具有统计学意义（p = 0.0007）。PS76A2治疗后GLQ - 8总分提高了28.9±154.6，安慰剂治疗后降低了94.8±141.1（p<0.0001）。PS76A2治疗后斯皮策单分量表提高了12.2±30.7，安慰剂治疗后降低了10.8±26.1（p<0.0001）。在无化疗的随访期后，通过FACT - G、GLQ - 8和斯皮策单分量表确定了有利于PS76A2的显著治疗差异。在该试验中，PS76A2耐受性良好，PS76A2组有17.6%的患者出现轻微局部反应。总之，PS76A2（15 ng槲寄生凝集素/0.5 ml，每周两次）在改善乳腺癌患者化疗及随访期间的生活质量方面被证明是安全有效的。
