Novel Regimen May Eliminate Need for Radiation in Some Oropharyngeal Cancers

Robert Siegel, MD, discusses the 13-month follow-up of the combination of induction chemotherapy and transoral surgery in oropharyngeal squamous cell carcinoma.

Robert Siegel, MD

The standard of care for oropharyngeal cancer is chemotherapy plus radiation, or surgery with adjuvant radiation. While effective, this level of radiation is often detrimental to a patient’s quality of life, says Robert Siegel, MD.

“These are young people in their 40s and early 50s, and radiation beats them up forever. It’s not like you bounce back, you always know the difference after you've had a big dose of radiation,” said Siegel.

In a phase II study presented at the 2017 ASCO Annual Meeting, the efficacy of induction chemotherapy and transoral surgery was studied as a definitive treatment for locally advanced oropharyngeal squamous cell carcinoma.

Patients were treated with a combination of cisplatin and docetaxel before surgery. Induction therapy was followed by transoral and neck resections through the da Vinci robotic-assisted surgery technique.

Through this regimen, Siegel hopes to eliminate the morbidity of radiation that plagues patients’ quality of life long after they are treated.

OncLive: Can you provide some background information on the treatment of this disease?

In an interview with OncLive during ASCO, Siegel, lead study author and chair, professor of medicine, director, Division of Hematology/Oncology, George Washington University, discussed the 13-month follow-up of the combination of induction chemotherapy and transoral surgery in oropharyngeal squamous cell carcinoma.Siegel: The standard of care for treating patients with oropharyngeal cancer—cancers of the base of the tongue, tonsil, other parts of the oropharynx—is a combination of weekly low-dose chemotherapy, usually cisplatin, and radiation. Most patients are cured, even with locally advanced disease, but the consequences of all of that radiation has long-term implications. Short-term, people have a difficult time eating, to the point where they often need a temporary feeding tube while they are getting radiation. And long-term, the radiation dries out your salivary glands, which means your mouth is dry and your sense of taste is forever altered in a negative way. [Radiation] has all types of implications for dental health, as well such as gum disease, and even sometimes the jawbone will begin to die.

Please provide an overview of this study.

The other issue is that head and neck cancer used to be a consequence of long-term smoking, and associated with a lot of alcohol intake. Nowadays, it is a different story. Most of the patients that we see are not there because they have had too much to drink or have smoked too much—it is HPV-associated. Most are men, not all, and the implications of high-dose radiation are more consequential because we are dealing with younger people. The idea of this study was to look at treatment in a different way. That is, instead of using the traditional low-dose weekly chemotherapy and radiation, what we have been doing—first informally and then in the past couple of years formally—is using standard doses of 2 chemotherapy drugs. And it turns out that HPV-associated cancers shrink much quicker than non-HPV associated cancers.

So, what we were finding was that after 3 doses of chemotherapy, the cancers were melting away to nothing. Subsequently, my close friend who is a head and neck surgeon would use this robot to remove whatever is left of the cancer, and also remove the lymph nodes in the neck—either 1 side or both sides.

With a mean of 17 months, most of the patients have done beautifully. At the time of surgery, almost three-fourths have no evidence of cancer in the primary site, and over two-thirds have no lymph node involvement.

The idea is to see if we can avoid the radiation, or use it only if we need to. The radiation is used if we do not get a good response initially, or if there are many lymph nodes involved at the time of surgery, or if there is relapse. We are trying to get the best of both worlds—we are trying to minimize toxicity and maximize quality of life, and at the same time have a safety net that will be there in case the cancer does not respond in the way that we’d hoped.

Things are looking very good right now, I would like to report that every single patient had complete response everywhere—we aren’t there but most patients are doing well. The patients that have been treated have no difference in quality of life—they can taste wine and good food, and have no more tooth decay or gum disease than anyone else.

The weakness of the study is that we are only a mean of 17 months out—we need more time. And, we need to get more people involved. This started as an idea, and I think it is gathering steam.

There is another aspect of this narrative that I also want to emphasize. In head and neck cancer, when people are using induction therapy—the use of chemotherapy drugs prior to surgery or radiation—there are 3 drugs that have been used. These are docetaxel, cisplatin, and 5FU. My observation after doing this for a few years, is that the 5FU adds far more side effects and toxicity than it does efficacy. And so, for this trial, we have decided to drop 5FU and keep docetaxel and cisplatin, which we think are the 2 most effective drugs with minimal toxicity. That seems to be working too—our results speak for themselves in terms of response rates and long-term follow-up, not recurring.

There is a lot of rehab involved [with radiotherapy] and sometimes people never do swallow properly. So, we are just motivated to see if we could do something different. What is not in the abstract, is that we—the head and neck surgeon and I—had done several patients as we were treating them off-protocol, and many of those patients are out 5 and 6 years now doing okay. But, this doesn’t count because it wasn’t an IRB-approved study like this trial.

What would you like community oncologists to take note of from this study?

Is there anything else about this study that you would like to emphasize?

I am excited, if we can get at least equal efficacy treating this cancer, but improve quality of life—it’s a small step forward.For the practicing physician, this is still research and it is up to my team, me, and hopefully other centers around the country to prove that this is equally effective as the standard of care. The drugs that are used for treating these patients are off-the-shelf drugs. The idea is investigational—the drugs and the doses are not. So, it would be a way of simplifying and helping your patients, not only to survive a very difficult cancer, but to maintain quality of life long-term. The surgery part—the use of the da Vinci robot is this new surgical technique, where the surgeon is actually in a different room. The robot allows the scalpels and all of the other instruments to have a wider range of movement than a surgeon’s wrist. The use of the robot to remove the primary tumor is a step forward, as well. Now, that is not isolated to this trial, people are beginning to use the technique. But, it has been integrated into a sort of modern way of treating this, because the alternative is a far more difficult surgery. So, the surgical part is important too.

Siegel RS, Rafei H, Joshi A, et al. Phase II study: Induction chemotherapy & transoral surgery as definitive tx for locally advanced oropharyngeal squamous cell carcinoma (OPSCC)—A novel approach. J Clin Oncol 35, 2017 (suppl; abstr 6078).