When Less Is More: Halving Chemo Keeps Testicular Cancer at Bay, Study Finds

Toxic side effects of chemotherapy have been a concern across cancer care, as researchers look for ways to minimize the doses needed to kill cancer cells—and keep them at bay—to limit both both short- and long-term effects, such as hair loss or cardiovascular events. In 2018, for example, the practice-changing TAILORx study showed how the use of a 21-gene assay could help some women with breast cancer avoid chemotherapy with endocrine therapy.

Now, a new study from the United Kingdom finds that chemotherapy given after surgery for an aggressive form testicular cancer could be reduced by half, without putting men at risk of recurrence.

The 111 trial, led by the Institute of Cancer Research (ICR), London, and the University Hospital’s Birmingham National Health Service Foundation Trust, studied 250 men with early-stage testicular cancer who faced a high risk of recurrence following surgery. Results appeared in the journal European Urology.

Testicular cancer is the most common cancer to be diagnosed in men as younger men—those younger than age 40—and it can be particularly aggressive. Advances in therapy have improved survival rates, but if young men have chemotherapy after surgery, they may live with side effects for decades.

As the authors state, the standard post-surgical treatment for these patients is 2 cycles of bleomycin, etoposide, and cisplatin, or BEP, or to watch and wait and treat with 3 cycles of BEP chemotherapy if cancer returns. Investigators wanted to examine recurrence rates for men treated with 1 cycle of BEP chemotherapy, compared with rates for those given 2 cycles in earlier studies.

The researchers found that only 3 men had their cancer return within 2 years after finishing treatment. The rate was 1.3% (95% CI, 0.3%-3.7%). In this new study, 41% of the patients had 1 or more serious side effect, such as an infection, sepsis or vomiting, but just 2.6% had long-term damage such as hearing loss. Grade 3-4 febrile neutropenia occurred in 6.8% of the patients.

The rate of cancer recurrence was nearly the same as that seen in earlier studies of men who had 2 cycles of chemotherapy, the researchers said.

“Men with testicular cancer who are at high risk of recurrence have generally been treated with 2 cycles of chemotherapy, but our new study found that 1 cycle was enough to stop the tumor from coming back,” Robert Huddart, PhD, professor of urological cancer at ICR, said in a statement.

“Reducing the overall dose of chemotherapy could spare young men who have their whole lives ahead of them from the long-term side effects, and also means they will need fewer hospital visits for their treatment,” he said. “This 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.”

Trials that examine cutting doses of cancer therapies are taking place across cancer care. The 2018 meeting of the American Society of Clinical Oncology, where TAILORx was presented, also saw results for a study of 4000 women with HER2-positive early breast cancer involving trastuzumab; women who received the drug for 6 months had a similar rate of disease-free survival as those who took the drug for a full year. The addition of trastuzumab to chemotherapy, while practice-changing in terms of survival, was known to increase cardiotoxic effects.

Developing short-term cancer regimens can also reduce “financial toxicity,” in which patients’ mental health, medication adherence, or personal finances are affected if they cannot afford their portion of the cost of treatment.

Reference

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 [published online January 1, 2019]. Euro Urology. doi: 10.1016/j.eururo.2019.11.022.