Capecitabine/Bevacizumab and Signs of Progression/Recurrence for mCRC


An expert elaborates on the importance of the capecitabine + bevacizumab combination therapy for metastatic colorectal cancer, as well as what signs of progression or recurrence to look for in patients.

Tanios Bekaii-Saab, MD, FACP: Maintenance strategy has to be part of our primary strategies for patients with colorectal cancer. We’ve recently published multiple studies and a network meta-analysis summarizing findings from thousands of patients who have been part of these randomized studies. One thing consistent across the board is that maintenance therapy does better than not stopping or treating to toxicity or to progression. In terms of progression-free survival [PFS], maintenance therapy seems to get the edge over observation. Although it’s intriguing to see that survival didn’t seem to be affected much by observation vs maintenance, I still favor maintenance therapy. There are small hints of a survival trend, primarily because it delays progression. Our maintenance strategies have become relatively safe for patients, and patients can live a little more normally with those strategies.

My favorite is capecitabine plus bevacizumab. That makes it relatively easier on patients. The way I do it is the CAIRO2 study did daily capecitabine nonstop, which is tough to do in our US practice because continuous capecitabine without any interruption is tough on patients. There are multiple reasons for that beyond this discussion, but that’s something that’s been established. The way I go with a low-dose capecitabine is 5 days a week, Monday through Friday. That makes it easier on patients. A lot of our patients are older. Sometimes they don’t have the same level of support, but also they get tired on the chemotherapy. They’re a little foggy at times. We have to make it easy on them while maintaining the activity.

My go-to has been 5 days on, 2 days off: Monday through Friday and weekends off. That makes it easy to remember and gives these little breaks here and there for the patients. In my experience, this has worked well for the patients with little toxicities. In the long run, you can still see the hand-foot syndrome, but that’s relatively manageable for many patients. That’s been my go-to. You can question whether bevacizumab is needed. The studies haven’t supported the use of bevacizumab 1 way or the other, but that’s certainly an option that I like to add. It goes from every 2 weeks to every 3 weeks, so the patient doesn’t have to come to the clinic except every 3 weeks. Usually, we drop the infusion rate to 15 minutes at that time. It’s a quick in and out—a good quality-of-life piece.

On some occasions, the patient desires to completely forgo further chemotherapy. If we look at the maintenance strategies, they suggest that there’s no detriment to survival, although PFS may be shorter but not detrimental survival. I have that discussion with the patients, and many decide to proceed with a complete stop until progression and then start treatment again.

What do you do with maintenance therapy if patients progress? My rule of thumb is that if the patient progresses within 6 months of being on maintenance—definitely within 3 months—then I switch to a different combination. The patient started with FOLFOX [5-fluorouracil, leucovorin, oxaliplatin]–bevacizumab but switched to FOLFIRI [5-fluorouracil, leucovorin, irinotecan]–bevacizumab or vice versa. Why 3 to 6 months? We don’t know exactly where the line falls. It’s probably around 3 to 4 months. But because we have multiple options, I tend to consider reintroduction in much later lines of therapy instead of just reintroducing that. If it’s beyond 6 months, it’s likely that the tumor remains sensitive to oxaliplatin or irinotecan, whichever you started with, and I resituate the chemotherapy before taking other decisions.

This patient was switched to FOLFIRI [5-fluorouracil, leucovorin, irinotecan]–bevacizumab about 6 cycles from being on capecitabine-bevacizumab. This patient had persistent neuropathy, so the 6 cycles for capecitabine-bevacizumab are right there around the gray zone. Given that the patient had residual neuropathy, the decision was to switch to FOLFIRI [5-fluorouracil, leucovorin, irinotecan]–bevacizumab.

Anytime we assess patients, we assess based on a number of parameters. There’s the clinical presentation, the imaging, and biochemical testing. The most important piece is the clinical piece. The patient comes to you with more symptoms. That’s your first and most important red flag. If the symptoms aren’t toxicities related to the treatment, then you must be concerned about progression. Imaging is very important in that equation, especially the extent of progression. I use labs, CEA [carcinoembryonic antigen] specifically, as 1 factor. In the list of prioritization of what factors make the most sense, this 1 isn’t higher level. I use it. It’s a complement to the big picture. But let’s say someone is responding nicely on imaging, is feeling great clinically, and the CEA rises a little. I don’t care about the CEA frankly.

On the other hand, if the patient is clinically deteriorating, imaging is showing multiple new lesions and the CEA is stable, I don’t put too much credence in the CEA. The CEA can help with the gray zones when we have some progression—symptoms or the CEA shooting up. It may sway you 1 way or the other. At the end of the day, you have to put all these things together and try to make sense of all these elements before making a decision about switching to the next line of therapy.

This transcript has been edited for clarity.

Case: A 65-Year-Old Man With Metastatic Colorectal Cancer

Initial presentation

  • A 65-year-old man reported a 2-month history of constipation, bloating, abdominal pain, and 10-pound unintentional weight loss
  • PMH: Mild hypertension controlled with calcium channel blockers

Clinical workup

  • Labs: Hg 9.4 g/dL, LFTs elevated and CEA 80 ng/mL
  • Colonoscopy revealed a 5-cm completely obstructing mass in sigmoid colon
  • Patient underwent left hemicolectomy with diverting ostomy
  • Pathology: undifferentiated adenocarcinoma tumor invading through muscularis propria and extending into the pericolorectal tissue with5 of 12 resected nodes positive
  • CT scan showed several lesions in both lobes of the liver, measuring up to 15 mm in diameter, and 3 small lesions (<5 mm) in the left lower pulmonary lobe
  • Molecular testing: KRAS mutation in codon 12 of exon 2; microsatellite stable
  • Diagnosis: Stage 4 colorectal cancer
  • ECOG PS is 1


  • The patient received systemic therapy with FOLFOX + bevacizumab in the first line for 4 cycles
  • The patient developed neuropathy and was switched to capecitabine + bevacizumab for 4 months and then unfortunately progressed, residual neuropathy at G1
  • At that time he was switched to FOLFIRI + bevacizumab
  • 6 months later, clinical progression is confirmed when new lung metastases are seen on chest CT
  • The patient was switched to regorafenib
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