CBOP/BEP FOR TESTICULAR CANCER

Eur Urol. 2014 Jul 4. pii: S0302-2838(14)00608-3. doi: 10.1016/j.eururo.2014.06.034. [Epub ahead of print]

A Randomised Phase 2 Trial of Intensive Induction Chemotherapy (CBOP/BEP) and Standard BEP in Poor-prognosis Germ Cell Tumours (MRC TE23, CRUK 05/014, ISRCTN 53643604).

Huddart RA1, Gabe R2, Cafferty FH2, Pollock P2, White JD3, Shamash J4, Cullen MH5, Stenning SP2; for the TE23 Trial Management Group and Collaborators and the National Cancer Research Institute Testis Cancer Clinical Studies Group.

Author information

Abstract

BACKGROUND:

Standard chemotherapy for poor-prognosis metastatic nonseminoma has remained bleomycin, etoposide, and cisplatin (BEP) for many years; more effective regimens are required.

OBJECTIVE:

To explore whether response rates with a new intensive chemotherapy regimen, CBOP/BEP (carboplatin, bleomycin, vincristine, cisplatin/BEP), versus those in concurrent patients treated with standard BEP justify a phase 3 trial.

DESIGN, SETTING, AND PARTICIPANTS:

We conducted a phase 2 open-label randomised trial in patients with germ cell tumours of any extracranial primary site and one or more International Germ Cell Cancer Collaborative Group poor-prognosis features. Patients were randomised between 2005 and 2009 at 16 UK centres.

INTERVENTION:

BEP (bleomycin 30 000 IU) was composed of four cycles over 12 wk. CBOP/BEP was composed of 2×CBOP, 2×BO, and 3×BEP (bleomycin 15 000 IU).

OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS:

Primary end point was favourable response rate (FRR) comprising complete response or partial response and normal markers. Success required the lower two-sided 90% confidence limit to exclude FRRs <60 44="" 90="" achieve="" benchmark="" bep="" cbop="" contemporary="" equal="" frr="" gives="" if="" is="" numbers="" on="" p="" patients="" power="" randomised="" rates.="" response="" the="" this="" to="" true="" were="">

RESULTS AND LIMITATIONS:

A total of 89 patients were randomised (43 CBOP/BEP, 46 BEP); 40 and 41, respectively, completed treatment. CBOP/BEP toxicity, largely haematologic, was high (96% vs 63% on BEP had Common Terminology Criteria for Adverse Events v.3 grade ≥3). FRRs were 74% (90% confidence interval [CI], 61-85) with CBOP/BEP, 61% with BEP (90% CI, 48-73). After a median of 58-mo follow-up, 1-yr progression-free survival (PFS) was 65% and 43%, respectively (hazard ratio: 0.59; 95% CI, 0.33-1.06); 2-yr overall survival (OS) was 67% and 61%. Overall, 3 of 14 CBOP/BEP and 2 of 18 BEP deaths were attributed to toxicity, one after an overdose of bleomycin during CBOP/BEP. The trial was not powered to compare PFS.

CONCLUSIONS:

The primary outcome was met, the CI for CBOP/BEP excluding FRRs <61 3="" an="" and="" are="" but="" cbop="" confirmation="" data="" in="" international="" more="" os="" p="" pfs="" phase="" promising="" require="" toxic.="" trial.="" was="">

PATIENT SUMMARY:

In this study we tested a new, more intensive way to deliver a combination of drugs often used to treat men with testicular cancer. We found that response rates were higher but that the CBOP/BEP regimen caused more short-term toxicity. Because most patients are diagnosed when their cancer is less advanced, it took twice as long to complete the trial as expected. Although we plan to carry out a larger trial, we will need international collaboration.