Kehinde E O, Terry T R, Mistry N, Horsburgh T, Sandhu D P, Bell P R
Department of Urology, University of Leicester, Leicester General Hospital.
Cancer Surv. 1995;23:217-29.
New insights regarding the biology of hormone resistant CaP have shown that major growth factors other than testosterone are responsible for cellular proliferation of androgen resistant prostate cancer cells. In vitro studies have confirmed the efficacy of growth factor inhibitors such as suramin in reducing cellular proliferation of androgen dependent LNCaP and independent PC-3 CaP cell lines as well as CaP cells obtained by primary culture. Initial clinical trials using high dose suramin (peak serum concentration 250-300 micrograms/ml) as monotherapy in patients with hormone resistant CaP have shown some promise, but the duration of response to therapy has been short lived and suramin toxicity is a problem. To minimize toxicity without reducing anti-tumour activity, studies evaluating its use in combination with other cytotoxic drugs are attractive in CaP. Suramin and doxorubicin, tumour necrosis factor and EMP have shown synergy in vitro. However, in a phase II clinical trial using combination therapy with low dose suramin (140 micrograms/ml) and mitomycin C in 32 patients, there was one complete response and six partial responses, and in 15 patients, the disease had stabilized. The median time to treatment failure was 103 days, and the median survival was 209 days. This regimen caused significant toxicities. The present study has shown that the combination of EMP 280 mg twice a day and suramin 1 g weekly infusions for 6 weeks, compared to EMP 280 mg alone, showed a statistically significant difference in the rate of depression of PSA levels after 3 and 6 months of treatment (p < 0.01) and a statistically significant reduction in bone pain and requirement for analgesics in patients on combination therapy-100% compared to 0% for patients on EMP alone.
关于激素抵抗性前列腺癌生物学的新见解表明，除睾酮外的主要生长因子是雄激素抵抗性前列腺癌细胞增殖的原因。体外研究已证实，诸如苏拉明等生长因子抑制剂在减少雄激素依赖性LNCaP和非依赖性PC-3前列腺癌细胞系以及原代培养获得的前列腺癌细胞的细胞增殖方面具有疗效。在激素抵抗性前列腺癌患者中，使用高剂量苏拉明（血清峰值浓度250 - 300微克/毫升）作为单一疗法的初步临床试验已显示出一些希望，但治疗反应的持续时间较短，且苏拉明毒性是一个问题。为了在不降低抗肿瘤活性的情况下将毒性降至最低，评估其与其他细胞毒性药物联合使用的研究在前列腺癌治疗中具有吸引力。苏拉明与阿霉素、肿瘤坏死因子和EMP在体外已显示出协同作用。然而，在一项对32例患者使用低剂量苏拉明（140微克/毫升）与丝裂霉素C联合治疗的II期临床试验中，有1例完全缓解和6例部分缓解，15例患者病情稳定。治疗失败的中位时间为103天，中位生存期为209天。该方案导致了显著的毒性。本研究表明，与单独使用EMP 280毫克相比，每天两次服用EMP 280毫克并每周输注苏拉明1克，持续6周，在治疗3个月和6个月后，PSA水平下降率有统计学显著差异（p < 0.01），联合治疗患者的骨痛和镇痛药物需求与单独使用EMP患者相比有统计学显著降低 - 联合治疗患者为100%，单独使用EMP患者为0%。
