Results of this phase III trial could change the current standard of care for treating nonseminomatous or combined germ cell tumors of the testis.
A single cycle of adjuvant bleomycin, etoposide, and cisplatin (BEP) chemotherapy was shown to be as effective as the standard 2 cycles at reducing recurrence rates for nonseminomatous or combined germ cell tumors of the testis (NSCGCTT), according to a study published in European Urology.1
The single-arm, phase III trial enrolled 246 patients at 33 cancer centers in the UK between 2010 and 2014. The researchers administered a single cycle of 30,000 international units (IU) of bleomycin on days 1, 8, and 15, 165mg/m2 of etoposide on days 1 through 3, and 50 mg/m2 of cisplatin on days 1 and 2, plus an antibacterial and granulocyte colony stimulating factor. The 2-year malignant recurrence rate was 1.3% (95% CI, 0.3– 3.7), with a 4-year malignant recurrence rate of 1.8% (95% CI, 0.7–4.6), similar to rates reported from the administration of 2 cycles of BEP.
“Men with testicular cancer who are at high risk of recurrence have generally been treated with 2 cycles of chemotherapy,” study author Robert Huddart, MD, of the Institute of Cancer Research, London, UK, said in a press release.2 “But our new study found that 1 cycle was enough to stop their tumor from coming back.”
The primary endpoint of the study was the malignant recurrence rate at 2-year follow up. Secondary endpoints included benign recurrence rate, overall recurrence rate, relapse free survival and overall survival. Of the 236 patients included in the analysis, 228 (97%) were followed up to at least 2 years. The trial aimed to exclude a rate of ³ 5% malignant recurrence rate. Median follow-up was 49 months, with 4 patients experiencing malignant recurrence at 6, 7, 13, and 27 months.
Neutropenia (32%) was the most commonly reported adverse event (AE), with 95 patients (41%) reporting at least one grade 3-4 AE. Other commonly reported AEs were leukopenia (17%), febrile neutropenia (6.8%) and thrombocytopenia (3.4%). Long-term AEs for the single cycle regimen was rare, occurring in fewer than 3% of patients.
Testicular cancer is the most common cancer among young men in Western populations, and the study authors noted that a reduced cycle of chemotherapy would spare patients the additional side effects that are commonly associated with that current standard of BEP treatment.
"This new trial is already changing clinical practice on a global scale and is set to improve patients' quality of life, as well as reducing the cost of testicular cancer treatment,” said Huddart in a statement, adding that “reducing the number of cycles and the dosage for chemotherapy…could save the NHS money and free up valuable hospital time and resources.
1. Cullen M, Huddart R, Joffe J, et al. The 111 Study: A Single-arm, Phase 3 Trial Evaluating One Cycle of Bleomycin, Etoposide, and Cisplatin as Adjuvant Chemotherapy in High-risk, Stage 1 Nonseminomatous or Combined Germ Cell Tumours of the Testis. Eur Urol. doi:10.1016/j.eururo.2019.11.022.
2. The Institute of Cancer Research. Half the amount of chemo prevents testicular cancer from coming back, new trial shows [news release]. https://www.icr.ac.uk/news-archive/half-the-amount-of-chemo-prevents-testicular-cancer-from-coming-back-new-trial-shows. Accessed January 3, 2020.