Baker L H, Frank J, Fine G, Balcerzak S P, Stephens R L, Stuckey W J, Rivkin S, Saiki J, Ward J H
J Clin Oncol. 1987 Jun;5(6):851-61. doi: 10.1200/JCO.1987.5.6.851.
The term soft tissue sarcoma refers to a large variety of malignant tumors arising in extraskeletal connective tissues that connect, support, and surround discrete anatomic structures. All visceral organs also contain a connective stroma that can undergo malignant transformation. Because of the histological similarities of this group of tumors and their relative rarity, treatment prescriptions for patients that have disseminated disease are most often uniform. In this study, we asked the question whether adding a third drug (cyclophosphamide or actinomycin D) to Adriamycin (Adr [Adria Laboratories, Columbus, OH])-(3,3-dimethyl-1-triazeno)- imidazole-4-carboxamide (DTIC) would improve the response rate and/or survival. A unique feature of this cooperative group clinical trial was the mandatory pathology review of the histological material. All patients of the Southwest Oncology Group between June 1, 1976, and November 17, 1979, who had a biopsy-confirmed diagnosis of a soft tissue sarcoma with convincing clinical or biopsy-documented evidence of metastatic disease were eligible for the study. Patients were randomized to receive (1) Adr, 60 mg/m2 intravenously, day 1, and DTIC, 250 mg/m2 every 3 weeks (104 patients); (2) Adr and DTIC as in (1) and cyclophosphamide, 500 mg/m2, day 1 (112 patients); or (3) Adr and DTIC as in (1) and actinomycin D, 1.2 mg/m2, day 1, (119 patients). There was no statistically significant difference in response rates (33%, 34%, and 24%) (P = .25). Median durations of response were 31 weeks in the Adr-DTIC arm, 26 weeks in the cyclophosphamide-DTIC-Adr arm, and 23 weeks in the Adr-DTIC-Actinomycin D arm (P = .78). Median durations of survival were 37, 42, and 50 weeks, respectively. Again, no statistically significant differences were observed (P = .59). Toxicities from each of these treatment arms were formidable and were equivalent. Prognostic factor analysis showed a prognosis based on bone marrow reserve, sex, and pathology subtype favorable to patients.
软组织肉瘤这一术语指的是发生于骨骼外结缔组织中的多种恶性肿瘤，这些结缔组织连接、支撑并环绕着离散的解剖结构。所有内脏器官也都含有可发生恶性转化的结缔组织基质。由于这类肿瘤在组织学上有相似性且相对罕见，对于患有播散性疾病的患者，治疗方案通常较为统一。在本研究中，我们探讨了在阿霉素（Adr [俄亥俄州哥伦布市阿德里亚实验室]）-（3,3 - 二甲基 - 1 - 三氮烯）-咪唑 - 4 - 甲酰胺（DTIC）基础上加用第三种药物（环磷酰胺或放线菌素D）是否会提高缓解率和/或生存率。该协作组临床试验的一个独特之处在于对组织学材料进行强制性病理复查。1976年6月1日至1979年11月17日期间，西南肿瘤协作组中所有经活检确诊为软组织肉瘤且有令人信服临床证据或活检记录证明有转移性疾病的患者均符合该研究标准。患者被随机分为三组接受治疗：（1）第1天静脉注射阿霉素60mg/m²，每3周给予DTIC 250mg/m²（104例患者）；（2）阿霉素和DTIC用药同（1），并在第1天给予环磷酰胺500mg/m²（112例患者）；或（3）阿霉素和DTIC用药同（1），并在第1天给予放线菌素D 1.2mg/m²（119例患者）。缓解率（分别为33%、34%和24%）无统计学显著差异（P = 0.25）。阿霉素 - DTIC组的中位缓解持续时间为31周，环磷酰胺 - DTIC - 阿霉素组为26周，阿霉素 - DTIC - 放线菌素D组为23周（P = 0.78）。中位生存持续时间分别为37周、42周和50周。同样，未观察到统计学显著差异（P = 0.59）。这些治疗组的毒性都很严重且相当。预后因素分析显示，基于骨髓储备、性别和病理亚型的预后对患者有利。
