Akaza H, Shimazaki J, Tashiro K, Kotake T, Okajima E, Kagawa S, Machida T
Dept. of Urology, University of Tsukuba.
Gan To Kagaku Ryoho. 1997 Jan;24(1):77-85.
Late Phase II clinical study with bropirimine (U-54461S), a novel oral antitumor agent that has interferon inducing and anti-proliferative activities, was conducted in patients with bladder CIS at 38 institutions nationwide. To investigate the efficacy and safety of the treatment, bropirimine was administered to the patients at the dose of 750 mg every two hours, three times a day, for three consecutive days with four-day drug withdrawal, based on the results of the preceding clinical studies up to early phase II. Among the 48 patients registered, 41 patients were evaluable for antitumor efficacy. Complete response (CR) was observed in 17 of them, no change (NC) in 18 patients, and progressive disease (PD) in 6 patients; so the efficacy rate was 41.5%. Classified by patient background, the efficacy rates were 58.3% (7/12) in patients with primary bladder CIS, 34.5% (10/29) in those with secondary bladder CIS, 45.5% (10/22) in those with Grade 3, and 23.8% (5/21) in those previously given chemotherapeutic agents or BCG by intravesical or other routes. Adverse drug reactions frequently observed were influenza-like symptoms such as fever and generalized malaise and gastrointestinal symptoms like anorexia and nausea/vomiting; these symptoms were all Grade 2 or milder. Abnormalities in laboratory tests, such as an elevation in GOT/GPT, neutropenia, and leukopenia were observed. These adverse effects were all tolerated by the patients. From the above results, bropirimine was considered to be a useful oral agent for the treatment of bladder CIS.
对新型口服抗肿瘤药物布罗匹明（U - 54461S）进行了II期晚期临床研究，该药物具有干扰素诱导和抗增殖活性。研究在全国38家机构中对膀胱原位癌（CIS）患者开展。为了研究该治疗方法的疗效和安全性，根据前期直至II期早期的临床研究结果，给予患者口服布罗匹明，剂量为每两小时750毫克，每日三次，连续服用三天，停药四天。在登记的48例患者中，41例患者可评估抗肿瘤疗效。其中17例患者出现完全缓解（CR），18例患者病情无变化（NC），6例患者病情进展（PD）；因此有效率为41.5%。按患者背景分类，原发性膀胱CIS患者的有效率为58.3%（7/12），继发性膀胱CIS患者为34.5%（10/29），3级患者为45.5%（10/22），先前接受过膀胱内或其他途径化疗药物或卡介苗（BCG）治疗的患者为23.8%（5/21）。常见的药物不良反应为流感样症状，如发热和全身不适，以及胃肠道症状，如厌食和恶心/呕吐；这些症状均为2级或更轻。观察到实验室检查异常，如谷草转氨酶/谷丙转氨酶升高、中性粒细胞减少和白细胞减少。这些不良反应患者均能耐受。根据上述结果，布罗匹明被认为是治疗膀胱CIS的一种有效口服药物。
