Foulke R S, Marshall M H, Trotta P P, Von Hoff D D
Brooke Army Medical Center, Division of Hematology/Oncology, San Antonio, Texas 78234.
Cancer Res. 1990 Oct 1;50(19):6264-7.
One hundred eighty-nine human tumor specimens were tested in a human tumor cloning assay to determine their growth response to human recombinant granulocyte-macrophage colony-stimulating factor. Of these samples 48 were evaluable for response. Growth stimulation to greater than 150% of controls was noted in 1 of 12 lung cancers (8%) and 1 of 14 breast cancers (7%) but in no other instances for an overall rate of 2 of 48 (4.2%). A dose-response effect was not seen with each of the two stimulated samples responding only at the two lowest concentrations tested. In addition, 7 cell lines derived from human tumors were tested using a metabolic CO2 production assay without evidence of growth stimulation. Samples of normal bone marrow displayed the usual dose-dependent stimulation whether grown in agar or assayed metabolically. We conclude that human recombinant granulocyte-macrophage colony-stimulating factor has minimal effect on the growth of the solid tumors tested and that clinical trials to reduce chemotherapy-associated myelo-suppression may proceed without undue concern for enhancement of tumor growth.
在一项人类肿瘤克隆试验中检测了189份人类肿瘤标本,以确定它们对人类重组粒细胞 - 巨噬细胞集落刺激因子的生长反应。在这些样本中,有48份可评估反应。在12例肺癌中有1例(8%)和14例乳腺癌中有1例(7%)观察到生长刺激超过对照的150%,但在其他情况下未观察到,总体发生率为48例中的2例(4.2%)。两个受刺激样本均未观察到剂量反应效应,且仅在测试的两个最低浓度下有反应。此外,使用代谢性二氧化碳产生试验检测了7种源自人类肿瘤的细胞系,未发现生长刺激的证据。正常骨髓样本无论在琼脂中生长还是进行代谢检测,均显示出通常的剂量依赖性刺激。我们得出结论,人类重组粒细胞 - 巨噬细胞集落刺激因子对所测试的实体瘤生长影响极小,并且在进行减少化疗相关骨髓抑制的临床试验时,无需过度担心肿瘤生长会增强。