Chugh Rashmi, Dunn Rodney, Zalupski Mark M, Biermann J Sybil, Sondak Vernon K, Mace Joseph R, Leu Kirsten M, Chandler William F, Baker Laurence H
University of Michigan Comprehensive Cancer Center, Ann Arbor, MI, USA.
J Clin Oncol. 2005 May 20;23(15):3597-604. doi: 10.1200/JCO.2005.02.170.
The purpose of this trial was to assess the objective clinical response, toxicity, and time to progression of treatment with 9-Nitro-Camptothecin (9-NC) in patients with advanced chordoma, soft tissue sarcoma (STS), and gastrointestinal stromal tumor (GIST).
Patients with locally advanced and/or metastatic chordoma, STS, or GIST received 9-NC 1.25 mg/m2 orally for 5 consecutive days followed by 2 days of rest. Patients continued on therapy until disease progression, uncontrollable toxicity, or withdrawal of consent.
From January 2000 to May 2003, 51 patients (15 chordoma, 23 STS, 13 GIST patients) enrolled. One patient (7%) with chordoma and one patient (4%) with STS had an objective response. Median time to progression was 9.9, 8.0, and 8.3 weeks for chordoma, STS, and GIST patients, respectively. Three- and 6-month progression-free survival rates were 47% and 33% for chordoma patients, 26% and 22% for STS patients, and 31% and 23% for GIST patients, respectively. Ten patients (10%) stopped study drug before disease progression secondary to toxicity. Common adverse events included anemia (42 patients, seven with grade 3/4 toxicity), leukopenia (33 patients, nine with grade 3/4 toxicity), fatigue (30 patients, three with grade 3/4 toxicity), nausea (34 patients, six with grade 3/4 toxicity), and diarrhea (28 patients, five with grade 3/4 toxicity).
9-NC has modest activity in delaying progression in patients with unresectable or metastatic chordoma. 9-NC is associated with moderate toxicity and shows little benefit in patients with advanced STS and GIST.
本试验旨在评估9-硝基喜树碱（9-NC）治疗晚期脊索瘤、软组织肉瘤（STS）和胃肠道间质瘤（GIST）患者的客观临床反应、毒性及疾病进展时间。
局部晚期和/或转移性脊索瘤、STS或GIST患者口服9-NC 1.25 mg/m²，连续5天，随后休息2天。患者持续接受治疗直至疾病进展、出现无法控制的毒性或撤回同意书。
2000年1月至2003年5月，共入组51例患者（15例脊索瘤、23例STS、13例GIST患者）。1例（7%）脊索瘤患者和1例（4%）STS患者出现客观反应。脊索瘤、STS和GIST患者的疾病进展中位时间分别为9.9周、8.0周和8.3周。脊索瘤患者的3个月和6个月无进展生存率分别为47%和33%，STS患者分别为26%和22%，GIST患者分别为31%和23%。10例（10%）患者在疾病进展前因毒性而停用研究药物。常见不良事件包括贫血（42例患者，7例为3/4级毒性）、白细胞减少（33例患者，9例为3/4级毒性）、疲劳（30例患者，3例为3/4级毒性）、恶心（34例患者，6例为3/4级毒性）和腹泻（28例患者，5例为3/4级毒性）。
9-NC在延缓不可切除或转移性脊索瘤患者疾病进展方面有一定活性。9-NC与中度毒性相关，对晚期STS和GIST患者益处不大。
