Bleomycin, vincristine, cisplatin/bleomycin, etoposide, cisplatin chemotherapy: an alternating, dose intense regimen producing promising results in untreated patients with intermediate or poor prognosis malignant germ-cell tumours

Abstract

Patients with poor and intermediate prognosis metastatic germ-cell tumours (MGCTs) are at a significant risk of relapse after standard platinum-based chemotherapy. Novel treatment regimens are required to improve survival. Dose intense, alternating combinations of drugs with known activity in germ-cell tumours represents one approach. In all, 43 patients with IGCCCG intermediate/poor prognosis MGCT were treated with a dose intense regimen alternating bleomycin, vincristine, cisplatin (BOP) with bleomycin, etoposide, cisplatin (BEP) to a maximum of three cycles. Data were collected on the maintenance of dose intensity, toxicity, response, progression-free (PFS) and overall survival (OS). The complete response rate was 58%; a further 7% of patients being rendered disease free by resection of viable residual tumour. With a median follow-up of more than 4 years in surviving patients, 3-year OS and PFS rates of 81% (95% CI: 66 -91%) and 72% (95% CI: 56 -83%) are seen, respectively. Bleomycin, vincristine, cisplatin (BOP)/bleomycin, etoposide, cisplatin (BEP) was well tolerated, with 86% of patients completing all planned courses. Toxicity was predominantly haematological with common toxicity criteria grade III neutropenia in 90% of patients. Cisplatin neuropathy and bleomycin-induced pulmonary toxicity represented the most significant nonhaematological toxicity. Bleomycin, vincristine, cisplatin (BOP)/bleomycin, etoposide, cisplatin (BEP) represents a practicable, well-tolerated, dose intense chemotherapy regimen with significant activity in intermediate and poor prognosis MGCT.

Experimental Mouse Model of Bleomycin‐Induced Skin Fibrosis

“…Bleomycin in the presence of iron and oxygen generates reactive oxygen species (ROS) and can damage DNA by causing single‐ and double‐strand breaks (Chen, Ghorai, Kenney, & Stubbe, ). Because of its anti‐proliferative properties, bleomycin is clinically used as a chemotherapeutic drug (Anthoney et al., ). In the body, bleomycin is inactivated by the enzyme bleomycin hydrolase.…”

Survival estimates of a prognostic classification depended more on year of treatment than on imputation of missing values

“…This underestimation limits the possibility to evaluate the results of currently conducted observational studies reporting on survival of patients with nonseminomatous germ cell cancer. For randomized controlled trials, this is not very problematic, because the effect of a treatment is directly compared with patients receiving another treatment; however, the results of nonrandomized phase II trials on dose-intensive or highdose chemotherapy for poor prognosis patients might be interpreted too optimistically when compared with the 5-year survival estimate of 50% for poor-prognosis patients in the IGCC classification [19][20][21][22][23]. The same holds for outcome research, in which case series are reported to evaluate the treatment and outcome in one center [24,25].…”

GAMEC – a new intensive protocol for untreated poor prognosis and relapsed or refractory germ cell tumours

“…On the basis of encouraging phase 2 data, several more complex regimens have been utilised for untreated patients, and these have generally intensified the drug cisplatin using a dose-dense approach (including BOP/BEP (Anthoney et al, 2004), CBOP/BEP (Christian et al, 2003)) or an approach in which additional agents are added (such as POMB/ACE; Bower et al, 1997). In certain patients, an etoposide dose of 500 mg m À2 is superior to 360 mg m À2 (Toner et al, 2001) (its absence from the initial few weeks of the BOP/VIP-B regimen may account for the failure to show an advantage of that treatment over BEP (bleomycin, etoposide and cisplatin); Kaye et al, 1998).…”