Budman D R, Berry D A, Cirrincione C T, Henderson I C, Wood W C, Weiss R B, Ferree C R, Muss H B, Green M R, Norton L, Frei E
Department of Medicine, North Shore University Hospital-New York University School of Medicine, Manhasset 11030, USA.
J Natl Cancer Inst. 1998 Aug 19;90(16):1205-11. doi: 10.1093/jnci/90.16.1205.
Both total dose and dose intensity of adjuvant chemotherapy are postulated to be important variables in the outcome for patients with operable breast cancer. The Cancer and Leukemia Group B study 8541 examined the effects of adjuvant treatment using conventional-range dose and dose intensity in female patients with stage II (axillary lymph node-positive) breast cancer.
Within 6 weeks of surgery (radical mastectomy, modified radical mastectomy, or lumpectomy), 1550 patients with unilateral breast cancer were randomly assigned to one of three treatment arms: high-, moderate-, or low-dose intensity. The patients received cyclophosphamide, doxorubicin, and 5-fluorouracil on day 1 of each chemotherapy cycle, with 5-fluorouracil administration repeated on day 8. The high-dose arm had twice the dose intensity and twice the drug dose as the low-dose arm. The moderate-dose arm had two thirds the dose intensity as the high-dose arm but the same total drug dose. Disease-free survival and overall survival were primary end points of the study.
At a median follow-up of 9 years, disease-free survival and overall survival for patients on the moderate- and high-dose arms are superior to the corresponding survival measures for patients on the low-dose arm (two-sided P<.0001 and two-sided P = .004, respectively), with no difference in disease-free or overall survival between the moderate- and the high-dose arms. At 5 years, overall survival (average +/- standard error) is 79% +/- 2% for patients on the high-dose arm, 77% +/- 2% for the patients on the moderate-dose arm, and 72% +/- 2% for patients on the low-dose arm; disease-free survival is 66% +/- 2%, 61% +/- 2%, and 56% +/- 2%, respectively.
Within the conventional dose range for this chemotherapy regimen, a higher dose is associated with better disease-free survival and overall survival.
辅助化疗的总剂量和剂量强度被认为是可手术乳腺癌患者预后的重要变量。癌症与白血病B组研究8541探讨了使用常规剂量范围和剂量强度的辅助治疗对II期（腋窝淋巴结阳性）女性乳腺癌患者的影响。
在手术（根治性乳房切除术、改良根治性乳房切除术或肿块切除术）后6周内，1550例单侧乳腺癌患者被随机分配到三个治疗组之一：高、中、低剂量强度组。患者在每个化疗周期的第1天接受环磷酰胺、多柔比星和5-氟尿嘧啶治疗，5-氟尿嘧啶在第8天重复给药。高剂量组的剂量强度是低剂量组的两倍，药物剂量也是低剂量组的两倍。中剂量组的剂量强度是高剂量组的三分之二，但总药物剂量相同。无病生存期和总生存期是该研究的主要终点。
在中位随访9年时，中剂量组和高剂量组患者的无病生存期和总生存期均优于低剂量组患者相应的生存指标（双侧P<0.0001和双侧P = 0.004），中剂量组和高剂量组之间的无病生存期或总生存期无差异。5年时，高剂量组患者的总生存期（平均±标准误）为79%±2%，中剂量组患者为77%±2%，低剂量组患者为72%±2%；无病生存期分别为66%±2%、61%±2%和56%±2%。
在该化疗方案的常规剂量范围内，较高剂量与更好的无病生存期和总生存期相关。
