I would start off with FOLFIRI and bevacizumab, considering the prior exposure to FOLFOX. I typically use the stop-and-go approach in a patient like this, for whom management is more important than trying to achieve resectable disease. I’d administer about 3 months of FOLFIRI/bevacizumab and then try to switch to 5-FU or capecitabine with bevacizumab. I would continue until disease progression and then restart the FOLFIRI.

I would generally not use bevacizumab in patients older than age 80 because of the higher risk for cardiovascular events in that age group.

I would consider FOLFOX or CAPOX + bevacizumab because it expands the opportunity for treatment. I discuss the possibility of neuropathy and inform patients that they have other options. If the patient experiences neuropathy I tend to drop the oxaliplatin.

The patient’s functional status is important. I discuss the option with patients who are healthy and tell patients they may experience some benefit. For patients who are in their eighties, the addition of bevacizumab does give me pause. Older individuals who have cardiac risk factors must be made aware that they would be at a higher risk for cardiac events.

I often use FOLFIRI/bevacizumab, although FOLFOX/bevacizumab is also an option. Even though 12 months is often the accepted time frame from completion of adjuvant therapy, because I feel FOLFIRI/bevacizumab is a perfectly legitimate regimen I’ll often be persuaded to use it in this setting.

I continue treatment until the patient can’t tolerate it or the disease progresses. After about 6 months of FOLFIRI, patients start to develop gastrointestinal side effects such as diarrhea. This may be an occasion when I switch to a fluoropyrimidine and bevacizumab. But that is uncommon.

The original studies suggested that age was a predictor for cardiovascular events. However, I don’t use a particular age as a cutoff in my practice.

I would use FOLFIRI and bevacizumab in this scenario. If patients have minimal disease and are asymptomatic, I sometimes offer treatment breaks. If patients have aggressive or widespread disease, I often continue treatment indefinitely. Most patients experience neuropathy, so I generally drop back to 5-FU/bevacizumab as maintenance.

Age is not relevant to my decision to use bevacizumab.

FOLFIRI/bevacizumab is well tolerated and is a pretty standard regimen, so that’s what I use in this scenario with the thought that I could always go back to an oxaliplatin regimen later.

I would treat until disease progression. I use an induction maintenance therapy approach, even with an irinotecan-based regimen. I try to limit combination chemotherapy with FOLFOX or FOLFIRI to about 8 cycles and continue maintenance with a fluoropyrimidine/bevacizumab combination.

My decision to use bevacizumab would depend on the patient’s fitness and comorbidities, not on age.

I would restart the FOLFOX and add bevacizumab and would continue treatment depending on how symptomatic the patient is and how good the response is. On average, I treat with oxaliplatin for about 4 months and then continue the 5-FU/bevacizumab without oxaliplatin. The paradigm that most of us use tends to favor an oxaliplatin regimen first line and an irinotecan-based therapy in the second-line setting, and I like to stay within that paradigm. In general, I believe that an oxaliplatin regimen tends to be better tolerated and results in more tumor shrinkage.

Generally patient age is not a consideration for the use of bevacizumab. If the patient had bad vascular disease, then I would discuss the use of bevacizumab more carefully. In my opinion, a fluoropyrimidine with bevacizumab is much better than either oxaliplatin or irinotecan for older patients.

I believe that many of the treatment options available are more similar than different. My choice would depend on patient performance status and if they had a contraindication to a particular regimen. For a patient with a good performance status FOLFOX, CAPOX or FOLFIRI in combination with bevacizumab would be feasible. Depending on the patient’s preference for toxicity I would choose either an oxaliplatin- or irinotecan-based regimen. The advantage of using an oxaliplatin regimen first, as long as we had a good window of time and it was effective, is that I can often recycle it if it's withheld because of toxicity. Many patients prefer the risk of neuropathy in the beginning — rather than experiencing neuropathy itself — to the risk of alopecia and diarrhea. I work with a good team, so I'm comfortable with stopping the oxaliplatin before it reaches a level of neuropathy that the patient would regret. I treat until the disease progresses.

Age itself is not a consideration for the use of bevacizumab. The main issue is whether they have comorbidities that track with age. If the patient had a heart attack and was older, that would be a concern.

In this case, I would generally recommend a different chemotherapy backbone, namely FOLFIRI with the addition of bevacizumab. In the absence of disease progression, I would continue treatment indefinitely. I often employ a stop-and-go technique with either the oxaliplatin or the irinotecan to make it more tolerable, with the patient receiving the drug for 3 months and going off it for 3 months. So, if a patient is having a good response and is tolerating it well, I keep the oxaliplatin or the irinotecan going for a longer period. If they only achieve stable disease or their response stabilizes after a few more cycles, then I will consider a lower threshold to simply drop it.

Typically, 12 months is the cutoff in deciding whether to treat again with FOLFOX. I review 2 factors in making a decision. First, how long has it been since they received the treatment and does it still have any efficacy? Second, how was the treatment tolerated? If the patient did not fare well on oxaliplatin, I choose an irinotecan-based regimen. If the patient reported no problems, then I have a lower threshold to go back to it.

I don’t believe in a specific age at which I would not consider using bevacizumab.