Prognostic analysis of Japanese men with metastatic germ cell tumors showing favorable response to bleomycin, etoposide and cisplatin as first-line chemotherapy

Abstract

The objective of this study was to evaluate the efficacy of first-line bleomycin, etoposide and cisplatin (BEP) chemotherapy in Japanese patients with metastatic germ cell tumors (GCTs). Between 1996 and 2006, 88 male patients with metastatic GCTs were treated with first-line BEP at our institution. Of these 88, 47 (16, seminoma; 31, nonseminoma), who did not receive high-dose chemotherapy following BEP because of the normalization of serum tumor markers, were included in this study. The primary site was the testis in 42 patients, retroperitoneum in 3, and mediastinum in 2. The full-dose regimen used for BEP consisted of cisplatin 20 mg/m2 on days 1 to 5, etoposide 100 mg/m2 on days 1 to 5, and bleomycin on days 2, 9 and 16. Therapeutic outcome was assessed according to several clinicopathological parameters. Following 2 to 4 cycles of BEP (median, 4 cycles), alpha-fetoprotein, beta-human chorionic gonadotropin and lactate dehydrogenase were normalized in all 47 patients. Eighteen patients (38.3%) achieved a complete response (CR) after BEP alone, while BEP resulted in a partial response and stable disease in the remaining 23 (48.9%) and 6 (12.8%), respectively. In addition, surgical resection of the residual tumors following BEP was performed in 15 patients, of whom 12 (80.0%) and 3 (20.0%) achieved pathological and surgical CR, respectively. At a median follow-up of 27 months, all patients were alive; however, disease recurrence occurred in 5 (seminoma, 1; nonseminoma, 4), and all these 5 were subsequently treated with high-dose chemotherapy as salvage therapy. In this series, 1-, 3- and 5-year recurrence-free survival rates were 95.0, 91.4 and 79.2%, respectively, and, there was no significant difference in recurrence-free survival between patients with seminoma and those with nonseminoma. These findings suggested that patients with metastatic GCTs, regardless of histological subtype (i.e., seminoma or nonseminoma), who showed favorable response to first-line BEP chemotherapy, could achieve an excellent prognostic outcome.

1996年から2006年の間に初回化学療法としてブレオマイシン, エトポシドおよびシスプラチン併用化学療法(BEP療法)を施行した転移性胚細胞腫瘍 88例中, BEP療法に対して良好な反応を示したため, 引き続き大量化学療法を施行しなかった47例を対象に, その治療成績を検討した。47例の組織型はセミノーマおよび非セミノーマが, それぞれ16および31例で, 原発部位は精巣, 後腹膜および縦隔が, それぞれ42, 3および2例であった。BEP療法を 2～4コース(中央値, 4コース)施行後, AFP, β-HCGおよびLDHは全例において正常化し, 18, 23および6例を, それぞれCR, PRおよび SDと診断した。残存病巣を有する29例中15例に対して外科切除を施行し, 12および3例が, それぞれ病理学的および外科的CRと診断された。経過観察期間の中央値は27ヵ月で全例が生存中であるが, 5例に再発を認めた。再発症例には, 救済化学療法として大量化学療法を全例に施行した。47例の1, 3および5年非再発率は, それぞれ95.0, 91.4および79.2%であり, セミノーマおよび非セミノーマ症例の非再発率に有意差を認めなかった。以上より, 初回化学療法としてのBEP療法に良好な反応を示した転移性胚細胞腫瘍症例に対しては, 必要に応じて外科療法および強力な救済化学療法を追加することで, 優れた治療成績を挙げることが可能であるものと考えられた。