Practical Considerations in Chemotherapy Regimens for Pancreatic Cancer

Transcript:Tanios Bekaii-Saab, MD: When looking at the regimens that are available to us today, whether it’s FOLFIRINOX or gemcitabine/nab-paclitaxel, there have been multiple studies that looked at different ways to modify treatment. Most of these studies have been retrospective to modify the standard schedule and dose, and most of them are based on institutional biases. With FOLFIRINOX, there have been multiple retrospective looks at modified FOLFIRINOX. Dropping the dose of the oxaliplatin and the irinotecan, and dropping the bolus 5-FU/leucovorin, has improved the tolerability a little bit. But, it’s still a tough regimen.

With the gemcitabine/nab-paclitaxel, there has been a study conducted by our group actually that was presented at ASCO GI a couple of years ago—and is about to be published—that looked at the every-other week modified regimen of gemcitabine/nab-paclitaxel. This was, again, a retrospective look; although, it came from a prospectively collected database, and looked at all our patients who were treated with the every-other week regimen rather than the weekly regimen. So, we skipped day 8. And at least in our study, which has its limitations in terms of its retrospective nature, and number of other limitations that come with these types of studies, the other every-week regimen seems to perform historically as well as the weekly gemcitabine/nab-paclitaxel. And so, depending on the prescribing physicians, some folks, like myself, would prefer the every-other week regimen for most patients. But, others would limit this to patients who may be borderline performance status, and, therefore, less likely to take the intense regimen because it’s a little bit better tolerated. And others just still go with a weekly regimen.

Until there’s a study that compares the two, it’s very difficult to say whether this is the correct strategy. Other strategies have also been looked at, such as week 1, week 2, so day 1, 8, and skip day 15. Others would lower the dose. So, there are different strategies that have been adopted by multiple other institutions. Although, again, there’s nothing that’s been presented or published other than the bi-weekly regimen, which seems to historically perform as well.

Philip A. Philip, MD: Using nab-paclitaxel/gemcitabine combination, which is now becoming more and more popular because there is a large number of patients who can get this treatment, as opposed to the FOLFIRINOX, which is a more aggressive treatment in my opinion. It has more side effects, which may not be so apparent when you read the literature. But, in reality, you do see more side effects, at least in my experience. I see more patients who are admitted to the hospital with FOLFIRINOX side effects than I have for nab-paclitaxel/gemcitabine.

Having said that, the nab-paclitaxel/gemcitabine regimen combination treatment also has its own problems. It has side effects, and these side effects can get worse with time. We call them cumulative toxicities, and these include the neuropathy and the fatigue. Fatigue is a very important side effect because it really affects the quality of life of the patients in a significant way, even in the absence of someone having neuropathy or myelosuppression. The every-other week treatment helps us a lot because it minimizes that side effect, so we get less fatigue as a cumulative side effect. We also get less neuropathy, because we’re exposing the patients less to nab-paclitaxel. And the other side effects like the myelosuppression, neutropenia, or thrombocytopenia certainly are much better managed that way, to the point that we don’t need to use growth factors to support those patients with neutropenia—something which some practitioners use when they’re using the 3 weeks on, 1 week off regimen. Overall, it is a good regimen to apply to patients.

However, one has to keep in mind that the published study was not every-other week. So, we don’t know if the every-other week is also going to be compromising the efficacy of the regimen, because patients will be exposed to less of the drug and, also, to a different schedule. The way I approach the every-other week regimen is I use it certainly in patients who have been started on the regular standard treatment. Then after a while, because they are doing well, their disease has been controlled, and now they’re starting to get some difficulties with the treatment, then I convert them to every-other week.

Sometimes I have older patients who come to me whose performance status is borderline. I will start them right away on the every-other week regimen. The every- other week regimen still is not a standard for every patient to be applied. This is something that we have to be mindful of, that we can’t use it for every single patient we see. But, at the same time, it’s something we can use. And, in fact, it helps patients to continue treatment longer.

I have an 82-year-old gentleman who had a good response to initial treatment, but within the first 4 months was starting to suffer from increasing fatigue. I put him on every-other week. Now, it’s 14 months later, about 10 months on the every-other week, and it’s controlling the disease. And he’s a very happy guy.

Transcript Edited for Clarity