Study supports weekly low-dose cisplatin for advanced head and neck squamous cell carcinoma

Patients with locally advanced head and neck squamous cell carcinoma who received weekly low-dose cisplatin with concurrent radiotherapy achieved the same survival as those who received standard high-dose cisplatin every 3 weeks plus radiotherapy, according to study results published in Journal of the National Cancer Institute.

However, patients who received the low-dose weekly regimen — commonly used in the United States — experienced considerably less toxicity.

“These results validated our clinical practice,” Joshua M. Bauml, MD, assistant professor of hematology/oncology at Perelman School of Medicine at University of Pennsylvania, told HemOnc Today. “They are reassuring and support what we have been doing, and I think this is great news for patients.”

Concurrent chemoradiotherapy is a key component of treatment for patients with locally advanced HNSCC who do not undergo surgery.

The standard cisplatin dose of 100 mg/m² every 3 weeks has been associated with clinically significant toxicity. The desire for a more tolerable regimen led to widespread use of lower-dose cisplatin; however, these two approaches have not been compared extensively in randomized trials.

Bauml and colleagues retrospectively reviewed population-based data from the VA health system to assess outcomes of patients with stage III through stage IVB HNSCC who underwent definitive-intent chemoradiotherapy with either high-dose cisplatin (80 mg/m² to 120 mg/m²) or low-dose cisplatin (30 mg/m² to 50 mg/m²).

For the intention-to-treat analysis, researchers assigned patients to the high-dose or low-dose groups based on the dose administered in their first cycle.

The analysis included 2,901 patients, 2,200 of whom received high-dose cisplatin (mean initial dose, 100 mg/m²) and 701 of whom received low-dose cisplatin (mean initial dose, 40 mg/m²).

After researchers adjusted for propensity score, they observed no significant difference in OS with high-dose cisplatin (HR = 0.94; 95% CI, 0.8-1.04). However, patients who received the high-dose regimen appeared more likely to experience acute kidney injury, neutropenia, dehydration/electrolyte disturbance or hearing loss.

“The results really highlight the best possible situation — equivalent efficacy but less toxicity,” Bauml said. “That’s what we’re always hoping for. Based upon this, I feel it would be reasonable to consider the use of weekly cisplatin at 40 mg/m² for [this patient population].”

A randomized controlled trial conducted in India compared cisplatin administered weekly vs. every 3 weeks among patients with head and neck cancer. Results of that study showed the weekly regimen was associated with inferior PFS.

“It is important to remember these were very different populations,” Bauml said.

For example, the study conducted in India used a median cisplatin dose of 30 mg/m², whereas the most common dose in the U.S. is 40 mg/m².

“That doesn’t seem like a large difference but, if you understand this is given once a week and then extended over a 7-week course, that is a big difference in cisplatin dose,” Bauml said.

Also, more than 90% of patients included in the study in India underwent surgery for oral cavity cancers.

“I believe our study more accurately represents what we see in the United States in terms of nonoperative management of head and neck cancer,” Bauml said.

Bauml emphasized that a randomized controlled trial in an appropriate patient population is the best way to expand use of the low-dose regimen in practice.

Moving forward, he and colleagues plan to conduct additional research using VA data to assess the use of weekly dosing in the adjuvant setting.

“One of the limitations of the VA registry is that it does not have p16 data built into it,” Bauml said. “Most of the patients in the VA registry are current or former smokers, so the likely impact of that is limited; however, we’re doing some advanced registry diagnostics to try to evaluate the impact of p16.” – by Scott Buzby

Reference:

Bauml JM, et al. J Natl Cancer Inst. 2018;doi:10.1093/jnci/djy133.

For more information:

Joshua M. Bauml , MD, can be reached at joshua.bauml@uphs.upenn.edu.

References: A grant from NCI funded this study. Please see the study for all authors’ relevant financial disclosures.