Edmonson J H, Ebbert L P, Nascimento A G, Jung S H, McGaw H, Gerstner J B
Mayo Clinic, Rochester, Minnesota 55905, USA.
Am J Clin Oncol. 1996 Dec;19(6):574-6. doi: 10.1097/00000421-199612000-00008.
Because of its unusual mechanism of action, docetaxel was selected for study in advanced soft tissue sarcomas of adults as part of a search for new active antisarcoma agents. Patients at least 18 years old with measurable histologically proven advanced nonosseous sarcomas were enrolled if they had ECOG performance status of < or = 2 and satisfactory leukocyte and platelet counts, and hepatic and renal function. Patients with Kaposi's sarcoma, mesothelioma, meningioma, embryonal rhabdomyosarcoma, and extraosseous Ewing's sarcoma were excluded, as were patients with brain or leptomeningeal metastases. Other specific contraindications to participation included other active cancer, previous or concurrent cancer chemotherapy or immunotherapy, and known allergy to the drug vehicle, polysorbate 80. Women of childbearing potential were required to have a negative pregnancy test. Following premedication with dexamethasone and diphenhydramine hydrochloride, docetaxel 100 mg/m2 as a concentrated solution containing 40 mg/ml in polysorbate 80 was infused over 1 h in 250 ml of either dextrose 5% in water or 0.9% saline. Treatment was repeated at 3-week intervals using standard definitions for objective responses. Up to two separate 25% toxicity directed dose reductions were permitted. Between May and December 1993, nine men and nine women registered (median age, 44 years). They received a total of 51 cycles of docetaxel (median, 2.5 cycles). Toxicity included moderate leukopenia (median first cycle nadir, 1.5 x 10(9)/L) but no significant thrombocytopenia. Alopecia, diarrhea, nausea, vomiting, and anorexia were common side effects. Fever, minor skin rashes, stomatitis, and edema were also observed. One drug-related death occurred in a neutropenic patient. One partial regression was observed (5.9%, 95% C.I. 0.15-28.7%) among the 17 eligible patients in a patient with metastatic uterine leiomyosarcoma.
由于多西他赛独特的作用机制，作为寻找新型活性抗肉瘤药物的一部分，它被选用于成人晚期软组织肉瘤的研究。年龄至少18岁、组织学确诊为晚期非骨源性肉瘤且可测量的患者，若其东部肿瘤协作组（ECOG）体能状态≤2、白细胞和血小板计数以及肝肾功能良好，则可入组。卡波西肉瘤、间皮瘤、脑膜瘤、胚胎性横纹肌肉瘤和骨外尤因肉瘤患者被排除，脑或软脑膜转移患者也被排除。参与研究的其他特定禁忌证包括其他活动性癌症、既往或同时进行的癌症化疗或免疫治疗，以及已知对药物载体聚山梨酯80过敏。有生育潜力的女性需妊娠试验阴性。在用地塞米松和盐酸苯海拉明进行预处理后，将100mg/m²多西他赛以含40mg/ml聚山梨酯80的浓缩溶液，在250ml 5%葡萄糖水溶液或0.9%生理盐水中于1小时内输注。使用客观缓解的标准定义，每3周重复治疗。允许进行多达两次单独的25%毒性导向的剂量减少。1993年5月至12月期间，9名男性和9名女性登记入组（中位年龄44岁）。他们共接受了51个周期的多西他赛治疗（中位周期数2.5个）。毒性包括中度白细胞减少（中位首个周期最低点，1.5×10⁹/L），但无明显血小板减少。脱发、腹泻、恶心、呕吐和厌食是常见副作用。还观察到发热、轻微皮疹、口腔炎和水肿。1例中性粒细胞减少患者发生1例与药物相关的死亡。在17例符合条件的转移性子宫平滑肌肉瘤患者中，观察到1例部分缓解（5.9%，95%置信区间0.15 - 28.7%）。
