ORLANDO (EGMN) – The investigational agent tanespimycin offered clinical benefits to heavily pretreated patients with relapsed and refractory multiple myeloma when used with bortezomib in a phase I/II trial.

The combination resulted in a best response rate (defined as complete plus partial plus minor responses) in 27% of 67 evaluable patients who had failed a median of five prior regimens, Dr. Paul Richardson reported at the annual meeting of the American Society of Clinical Oncology. The best response rate reached 48% in 21 bortezomib-naive patients, 22% in 23 bortezomib-pretreated patients, and 13% in 23 patients refractory to bortezomib.

Kosan Biosciences Inc., the study sponsor, has been granted orphan drug status for tanespimycin, a heat shock protein–90 inhibitor, in both the United States and Europe.

Duration of response was particularly impressive in the phase I/II setting, reaching a median of 12 months in all responders and 27 months in bortezomib-naive patients, said Dr. Richardson, clinical director of the multiple myeloma center at the Dana-Farber Cancer Institute in Boston. Median progression-free survival reached 7.2 months in bortezomib-naive patients, whereas overall survival was “quite robust” at 18 months for all 72 patients treated, he said.

Patients were treated at escalating doses, reaching a high of 340 mg/m² of tanespimycin and 1.0-1.3 mg/m² of bortezomib in 42 patients in the phase II expansion.

The rate of grade 3/4 neutropenia was 3%. All-grade peripheral neuropathy, constipation, and anorexia were reported in 21%, 21%, and 6% of patients, respectively, and no patients experienced these events as grade 3/4 events. The absence of severe peripheral neuropathy supports preclinical work that tanespimycin may be neuroprotective, Dr. Richardson said.

Kosan has launched TIME-1, an international, open-label phase III study comparing tanespimycin plus bortezomib to bortezomib alone in relapsed multiple myeloma. Another phase III study is planned to evaluate tanespimycin with bortezomib–based therapy as first-line treatment in multiple myeloma, said Dr. Richardson, who reported serving as an advisor and speaker for Millennium Pharmaceuticals Inc. and Celgene Corp., and as advisor to Bristol-Myers Squibb Co.

 

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奥兰多 (EGMN) —— 在I/II期临床试验中，试验药物坦螺旋霉素(tanespimycin)与硼替佐米(bortezomib)联合用药，可有效治疗接受高强度预处理的复发难治性多发性骨髓瘤患者。

 

67名患者入选该研究，这些患者既往接受过平均5次的治疗，但治疗都无效，该联合治疗的最佳有效率(定义为完全有效、部分有效或轻微有效) 为27%，Paul Richardson博士在美国临床肿瘤学会的年会上报告。21名没用过硼替佐米的患者的最好有效率为48%，23名采用硼替佐米预处理的患者为22%，23名硼替佐米难治性患者为13%。

 

该研究的赞助商Kosan Biosciences公司生产的坦螺旋霉素为热休克蛋白-90的抑制剂，在美国和欧洲已获得罕用药物的批准。

 

在I/II期试验中，有效持续时间尤其突出，在所有有效患者中平均为12个月，在没用过硼替佐米的患者为27个月，波士顿Dana-Farber癌症研究所的多发性骨髓瘤中心的临床部主任Richardson报告。没用过硼替佐米患者的无进展生存期平均为7.2个月，而所有接受治疗的72名患者，在18个月时总生存率仍“相当好”。

 

患者接受治疗的剂量逐步增加，在II期临床试验中，42名患者的最大剂量为坦螺旋霉素340 mg/m²和硼替佐米1.0~1.3 mg/m²。

 

3/4级中性粒细胞减少率为3%。所有级别的周围神经病变、便秘和食欲减退率分别为21%、21%和6%，没有患者出现3/4级病变。没有出现严重周围神经病变——这支持临床前的研究结果，坦螺旋霉素可能具有神经保护作用，Richardson博士说道。

 

Kosan发起了TIME-1研究，这是一项国际性、开放性、III期试验，在复发性多发性骨髓瘤患者中，对比坦螺旋霉素和硼替佐米联合用药与硼替佐米单独用药的疗效。另一项III期试验计划评价坦螺旋霉素和硼替佐米为基础的治疗，作为一线药物治疗多发性骨髓瘤，Millennium 和Celgene制药公司的顾问和发言人、百时美施贵宝公司的顾问Richardson博士说道。