Gelber R D, Goldhirsch A, Cavalli F
Dana-Farber Cancer Institute, Boston, Massachusetts.
Ann Intern Med. 1991 Apr 15;114(8):621-8. doi: 10.7326/0003-4819-114-8-621.
To evaluate a single cycle of adjuvant chemotherapy compared with longer duration chemotherapy for premenopausal women or chemoendocrine therapy for postmenopausal women with operable breast cancer using a quality-of-life-oriented end point, Q-TWiST (quality-adjusted analysis of TWiST: Time Without Symptoms and Toxicity).
Multicenter randomized clinical trial--International Breast Cancer Study Group (IBCSG: formerly Ludwig Group) Trial V.
IBCSG participating centers in Sweden, Switzerland, Australia, Yugoslavia, Spain, New Zealand, Italy, Germany, and South Africa.
Data were available for 1229 eligible patients with node-positive breast cancer who were randomized to receive one of three adjuvant treatments after at least a total mastectomy and axillary clearance.
Patients received either a single cycle of perioperative chemotherapy consisting of cyclophosphamide, methotrexate, fluorouracil, and leucovorin; or six cycles (6 months) of a conventionally timed chemotherapy consisting of cyclophosphamide, methotrexate, fluorouracil, and prednisone for premenopausal women or this combination plus tamoxifen for postmenopausal women; or both perioperative and conventionally timed chemotherapy for a 7-month course of adjuvant therapy.
At 5 years of median follow-up, patients who received the longer duration therapies had an improved 5-year disease-free survival percentage (53% compared with 36%; P less than 0.001) and 5-year overall survival percentage (73% compared with 63%; P = 0.001) compared with those who received the single perioperative cycle alone. By 3.5 years, the greater burden of toxic effects associated with the longer duration treatments was balanced by their superior control of disease. Within 5 years of follow-up, even after subtracting time with adjuvant treatment toxicity, patients gained an average of 2.2 months of Q-TWiST if treated with the longer duration therapies compared with the single cycle (P = 0.03). The gain for premenopausal patients was 2.8 months (P = 0.05), whereas the gain for postmenopausal women was 1.5 months (P greater than 0.2).
Six or seven months of adjuvant chemotherapy or chemoendocrine therapy improve both the quantity and quality of life for patients with node-positive breast cancer compared with a single short course of perioperative combination chemotherapy.
采用以生活质量为导向的终点指标——Q-TWiST（无症状和毒性时间的质量调整分析），评估可手术乳腺癌绝经前女性辅助化疗单周期与更长疗程化疗，或绝经后女性化疗内分泌治疗的效果。
多中心随机临床试验——国际乳腺癌研究组（IBCSG：原路德维希组）V期试验。
IBCSG在瑞典、瑞士、澳大利亚、南斯拉夫、西班牙、新西兰、意大利、德国和南非的参与中心。
1229例符合条件的淋巴结阳性乳腺癌患者的数据可供分析，这些患者在至少进行全乳切除和腋窝清扫术后被随机分配接受三种辅助治疗之一。
患者接受单周期围手术期化疗，包括环磷酰胺、甲氨蝶呤、氟尿嘧啶和亚叶酸钙；或六个周期（6个月）的传统定时化疗，绝经前女性使用环磷酰胺、甲氨蝶呤、氟尿嘧啶和泼尼松，绝经后女性在此基础上加用他莫昔芬；或围手术期化疗和传统定时化疗联合进行7个月的辅助治疗。
中位随访5年时，接受更长疗程治疗的患者5年无病生存率（53%对比36%；P<0.001）和5年总生存率（73%对比63%；P = 0.001）均高于仅接受单周期围手术期化疗的患者。到3.5年时，更长疗程治疗相关的更大毒性负担被其对疾病的更好控制所平衡。在5年随访期内，即使减去辅助治疗毒性时间，与单周期治疗相比，接受更长疗程治疗的患者平均获得2.2个月的Q-TWiST（P = 0.03）。绝经前患者的获益为2.8个月（P = 0.05），而绝经后女性的获益为1.5个月（P>0.2）。
与单周期短期围手术期联合化疗相比，可以提高淋巴结阳性乳腺癌患者的生活质量，延长其生存时间。
