Budd G T, Bukowski R M, Lichtin A, Bauer L, Van Kirk P, Ganapathi R
Department of Hematology/Medical Oncology, Cleveland Clinic Foundation, OH 44195.
Invest New Drugs. 1993 Feb;11(1):75-9. doi: 10.1007/BF00873916.
Pre-clinical and clinical studies have shown that trifluoperazine (TFP) can modulate multidrug resistance. We have performed a Phase II trial of TFP and doxorubicin in doxorubicin-naive patients with metastatic breast cancer. We hypothesized that TFP would inhibit the development of doxorubicin resistance, resulting in an increased rate of complete response or a prolongation in response duration. Twenty patients with metastatic breast cancer were treated every 3 weeks with TFP 5 mg by mouth every 6 hours on days 0-5 and doxorubicin 60 mg/m2/96 hr on days 1-4 by continuous intravenous infusion. The first 5 patients were treated with TFP 15 mg by mouth every 6 hours, but the dose was reduced to 5 mg every 6 hours when grade 3-4 extrapyramidal toxicity was noted in 3 of the first 5 patients. Thereafter, neurologic toxicity was grade 0-2. No complete and 9 partial responses were produced in 20 patients (45%). The median response duration was 17 weeks (range 7-112). The combination of trifluoperazine and doxorubicin did not seem to produce a response rate or duration markedly different than that expected for doxorubicin alone in patients with metastatic breast cancer. Alternative trial designs may be necessary in future clinical trials investigating the inhibition of acquisition of drug resistance.
临床前和临床研究表明，三氟拉嗪（TFP）可调节多药耐药性。我们对未接受过阿霉素治疗的转移性乳腺癌患者进行了TFP与阿霉素联合使用的II期试验。我们假设TFP会抑制阿霉素耐药性的发展，从而提高完全缓解率或延长缓解持续时间。20例转移性乳腺癌患者每3周接受一次治疗，在第0至5天每6小时口服5毫克TFP，在第1至4天通过持续静脉输注每96小时给予60毫克/平方米阿霉素。前5例患者每6小时口服15毫克TFP，但在前5例患者中有3例出现3-4级锥体外系毒性后，剂量减至每6小时5毫克。此后，神经毒性为0-2级。20例患者（45%）未出现完全缓解，9例出现部分缓解。中位缓解持续时间为17周（范围7-112周）。在转移性乳腺癌患者中，三氟拉嗪与阿霉素联合使用似乎并未产生明显高于单独使用阿霉素预期的缓解率或持续时间。在未来研究抑制耐药性获得的临床试验中，可能需要采用其他试验设计。
