Berger M, Habs M, Schmähl D
Int J Cancer. 1983 Aug 15;32(2):231-6. doi: 10.1002/ijc.2910320215.
The CMF regimen, which is clinically used in adjuvant therapy of breast cancer, is known to be carcinogenic in rats (Habs and Schmähl, 1981). To examine alternative regimens, a long-term carcinogenicity study was performed, using the VMF regimen as follows: V (i.v.), M (i.p.) and F (p.o.) at 0.8, 20 and 300 mg/m2, respectively. These doses and a half-dose regimen (0.5 VMF) were administered every 6 weeks to 80 rats (40 males, 40 females) in each of three groups. Group I served as an untreated control. Groups II, III and IV received 6 X VMF, 18 X 0.5 VMF and 18 X VMF, respectively. Unlike treatment with comparable doses of CMF, the present therapy did not result in an increased tumor rate or a change in tumor type over controls. The chemotherapeutic efficacy of VMF was compared with that of CMF by administering the following doses (mg/m2 i.p.) to groups of 20 rats bearing methylnitrosourea-induced primary mammary carcinomas: group 1:C (420), 2:V (2.1), 3:M (35) and F (350), 4:C (210), M (21) and F (280), 5:V (1.05), M (21) and F (280), 6: as in 4 except that C was given 24 h prior to M and F, 7: as in 5 except that V was given 24 h prior to M and F, 8: ovariectomy on day 1, 9: control group. Animals bearing a tumor volume of greater than or equal to 0.8 cm3 were randomly allocated to the individual groups (day 1) and subsequently treated on days 1, 8, 15 (V only) 22, and 29. After 5 weeks the following T/C values were recorded: group 1: 12.6%, 2: 80%, 3: 49%, 4: 42.8%, 5: 67%, 6: 49.2%, 7: 26.5%, 8: 45.5%. These results indicate a possible superiority of VMF over CMF, since the former exhibits little or no carcinogenicity at comparable therapeutic activity.
临床上用于乳腺癌辅助治疗的CMF方案已知在大鼠中具有致癌性（哈布斯和施马尔，1981年）。为了研究替代方案，进行了一项长期致癌性研究，采用如下VMF方案：静脉注射V、腹腔注射M和口服F，剂量分别为0.8、20和300mg/m²。这些剂量和半剂量方案（0.5VMF）每6周给予三组中的每组80只大鼠（40只雄性，40只雌性）。第一组作为未治疗的对照组。第二组、第三组和第四组分别接受6倍VMF、18倍0.5VMF和18倍VMF。与用相当剂量的CMF治疗不同，目前的治疗方法与对照组相比，并未导致肿瘤发生率增加或肿瘤类型改变。通过向20只患有甲基亚硝基脲诱导的原发性乳腺癌的大鼠组给予以下剂量（腹腔注射mg/m²）来比较VMF和CMF的化疗效果：第1组：C（420），第2组：V（2.1）、M（35）和F（350），第3组：C（210）、M（21）和F（280），第4组：与第3组相同，但C在M和F前24小时给药，第5组：V（1.05）、M（21）和F（280），第6组：与第4组相同，但V在M和F前24小时给药，第7组：卵巢切除（第1天），第8组：对照组。肿瘤体积大于或等于0.8cm³的动物在第1天随机分配到各个组，随后在第1、8、15天（仅V）、22天和29天进行治疗。5周后记录以下T/C值：第1组：12.6%，第2组：80%，第3组：49%，第4组：42.8%，第5组：67%，第6组：49.2%，第7组：26.5%，第8组：45.5%。这些结果表明VMF可能优于CMF，因为前者在相当的治疗活性下几乎没有致癌性。
