The evidence supporting this regimen comes from a prospective trial offering risk-adapted management to nonseminomatous testicular germ cell tumour patients who presented as stage 1. Patients with no evidence of venous invasion (VI) were assigned to surveillance, patients with evidence of VI were considered high risk and assigned to short term adjuvant chemotherapy (cisplatin 20 mg/m2 days 1 to 5, etoposide 100 mg/m2 days 1 to 5 and bleomycin 30 mg on days 2, 9 and 16). Eligibility criteria for this study were as follows: clinical stage 1 NSGCT, pT stage 1 to 3 according to TNM system, and orchidectomy within the last month. 42 patients without VI were placed in the surveillance group and 42 patients received adjuvant chemotherapy.
All patients were included in the acute analysis,r 25 of these patients were available for long term evaluation. The long term results of this prospective study are presented by Pont et al.r
Evidence from the 111 study demonstrated that single cycle of BEP was safe, and the 2-year malignant recurrence rate of 1.3% (at a median follow-up of 49 months) was consistent with that seen following two cycles of BEP. This single-arm study of 246 patients administered 100 mg/m2 of cisplatin over days 1-2, etoposide 500 mg/m2 over days 1-3, and bleomycin 30000 IU on days 1, 8 and 15.r
Efficacy
After a median follow up of 79 months, the relapse and survival rates after 2 courses of BEP are summarised in the table below.
Relapse and Survival Ratesr |
Number
(n=29) |
Percent |
Relapses |
2 |
7 |
Progression free survival |
27 |
93 |
Overall survival |
27 |
93 |
Cause-specific survival |
28 |
97 |
One relapsing patient developed a primary embryonal carcinoma with venous invasion and of differentiated teratomatous components and continued to further surgery (disease free at 71 months post orchidectomy), the other developed an isolated secondary embryonal carcinoma in the left iliac fossa at 8 months which infiltrated the pelvic bone (deceased at 47 months). Another patient developed SCC of the lung (no evidence of germ cell tumour, deceased 34 months.)r
Toxicity
No life threatening or severe adverse events were noted during or immediately after the two courses of BEP.
Toxicityr
(n=42)
|
Grade 0
(%) |
Grade 1
(%)
|
Grade 2
(%) |
Grade 3
(%) |
Haemoglobin |
90 |
10 |
- |
- |
Leukocytes |
- |
17 |
60 |
23 |
Platelets |
79 |
14 |
7 |
- |
Nausea/Vomiting |
69 |
26 |
5 |
- |
Alopecia |
- |
- |
14 |
86 |
Renal |
97.5 |
2.5 |
- |
- |
Peripheral neurotoxicity |
93 |
7 |
- |
- |
Pulmonary |
100 |
- |
- |
- |
Infection |
88 |
10 |
2 |
- |
Ototoxicity |
97.5 |
2.5* |
- |
- |
*transient tinnitus for 2 weeks
2 years after completing treatment six patients from the chemotherapy group fathered one child and one fathered 2 children, and 2 patients in the surveillance group fathered a child.