‘More Isn’t Always Better’ With Adjuvant Chemotherapy in Colon Cancer

Tammy Triglianos, DNP, ANP-BC, AOCNP

Adjuvant chemotherapy can significantly reduce the risk of recurrence for some patients with colon cancer, but it is important to tailor treatment to the individual patient, explained Tammy Triglianos, DNP, ANP-BC, AOCNP, during a presentation at JADPRO Live, the 2023 Annual APSHO Meeting.

Triglianos, who is a nurse practitioner with the University of North Caroline Lineberger Comprehensive Cancer Center and School of Nursing, discussed ways that nurse practitioners can optimize treatment outcomes for patients with colorectal cancer.

Alongside Mary B. Morgan, ANP-BC, AOCN, a nurse practitioner with the at UT Southwestern Medical Center, Triglianos walked through which patients will benefit most from adjuvant chemotherapy, whether oxaliplatin-based regimens should be used, and the ideal treatment length for these patients.¹

Which Patients Should Receive Adjuvant Therapy?

The nurses explained that the purpose of adjuvant chemotherapy in colorectal cancer is to eradicate micro-metastatic disease following surgery and thereby prevent cancer recurrence and cancer-related mortality. Generally, the chemotherapy is given within 4 to 6 weeks after surgery, as waiting to begin treatment after this 2-month period may delay the effectiveness and inhibit the benefit of the therapy.

The benefit of this approach is most clearly demonstrated in patients with stage III disease, she said.

Treating With Oxaliplatin

When it comes to adjuvant oxaliplatin, providers should consider the significant toxicity risk and reserve its use for robust individuals with a long life expectancy.

Triglianos explained that the MOSAIC trial (NCT00275210) showcased that adding oxaliplatin to a 6-month adjuvant regimen improved both disease-free survival (DFS) and overall survival (OS) in patients with stage III colon cancer.²

In the overall stage II population, there is no clear benefit with adjuvant FOLFOX, unless the patient also has high-risk disease, Triglianos explained. Signs that a patient’s disease is high risk may include a T4 lesion, obstruction or perforation at diagnosis, suboptimal lymph node retrieval, lymphovascular invasion, or perineural invasion.

Because it is a stronger regimen, oxaliplatin may reduce an individual’s risk of recurrence. However, it is difficult to predict what subset of elderly patients will benefit. For instance, in the ACCENT study, which analyzed 7 phase 3 trials, adjuvant oxaliplatin was not associated with improved DFS or OS in elderly patients. Its benefit was restricted to those who were 70 years or younger.³

In Clinical Practice

Triglianos presented some patient cases to illustrate when adjuvant treatment with oxaliplatin may or may not be appropriate.

The first example was of a 77-year-old male who presented to the emergency department after experiencing 3 weeks of bright red blood per rectum. He was immediately admitted for workup.

A colonoscopy revealed an infiltrative and ulcerated non-obstructing mass in the ascending colon. He proceeded to undergo a colectomy and was diagnosed with stage III colon cancer that was microsatellite stable (MSS). Afterwards, his care team prescribed adjuvant infusional 5-fluorouracil (5-FU).

In contrast, when presented with a 38-year-old female, the treatment choice varied. In this clinical example, the patient presented to the emergency room for acute onset abdominal pain and vomiting. A colonoscopy revealed a near obstructing mass in her sigmoid colon; she also had stage III microsatellite stable colon cancer. After undergoing a left hemicolectomy, her care team decided to prescribe her an adjuvant regimen of folinic acid, fluorouracil, and oxaliplatin (FOLFOX).

“As you can see, these 2 cases are quite similar,” Triglianos explained. “Both had stage III colon cancer that was microsatellite stable, but they received different adjuvant therapies. The obvious difference between these two cases is their age: one was 77 and the other 38.”

Clarifying Ideal Treatment Length

Patients with colon cancer may undergo 3 or 6months of adjuvant chemotherapy. However, according to Triglianos, “more isn’t always better.”

“There is substantial toxicity with oxaliplatin-based therapy, sometimes resulting in permanent neurotoxicity—regardless of age,” she explained.

The IDEA trial was a prospective analysis of 6 phase 3 trials. The objective was to determine whether 3 months of oxaliplatin/fluoropyrimidine-based therapy was noninferior to 6 months.

Although noninferiority was NOT confirmed, when separated, no difference was observed with capecitabine and oxaliplatin (CAPOX) between the shorter course or longer course adjuvant treatment lengths. When looking at OS at 5 years of follow-up, there was only a 1% difference between those who receive 3 months and 6 months of adjuvant CAPOX therapy.

Further, the rate of grade 3 or worse neurotoxicity was lower in the 3 months group vs the 6-month group—the rates were 3% vs 16% with 3 months of FOLFOX and 6 months of FOLFOX; and the rates were 3% vs 9% with 3 months and 6 months of CAPOX, respectively.

Based on these findings, 3 months of CAPOX or FOLFOX should be considered for patients with low-risk stage III disease, Triglianos concluded.

“It is unlikely that decreasing the duration of adjuvant therapy will significantly impact overall survival,” she concluded. “This conclusion is strengthened by the substantial reduction of toxicities, inconveniences, and costs associated with a shorter treatment duration. A risk-based approach and conversation with patients is necessary in determining the duration of adjuvant therapy.”

References

1. Morgan MD, Triglianos T. Optimizing the care of patients with colorectal cancer in clinical practice. Presented at: 2023 JADPROLive. November 9-12, 2023; Orlando, FL.
2. André T, Boni C, Navarro M, et al. Improved overall survival with oxaliplatin, fluorouracil, and leucovorin as adjuvant treatment in stage II or III colon cancer in the MOSAIC trial. J Clin Oncol. 2009;27(19):3109-3116. doi:10.1200/JCO.2008.20.6771
3. McCleary NJ, Meyerhardt JA, Green E, et al. Impact of age on the efficacy of newer adjuvant therapies in patients with stage II/III colon cancer: findings from the ACCENT database. J Clin Oncol. 2013;31(20):2600-2606. doi:10.1200/JCO.2013.49.6638
4. Grothey A, Sobrero AF, Shields AF, et al. Duration of adjuvant chemotherapy for stage III colon cancer. N Engl J Med. 2018;378(13):1177-1188. doi:10.1056/NEJMoa1713709
5. Sobrero AF, Andrew T, Meyerhardt JA, et al. Overall survival (OS) and long-term disease-free survival (DFS) of three versus six months of adjuvant (adj) oxaliplatin and fluoropyrimidine-based therapy for patients (pts) with stage III colon cancer (CC): final results from the IDEA (International Duration Evaluation of Adj chemotherapy) collaboration. J Clin Oncol. 2020;35(supple 15):4004 doi:10.1200/JCO.2020.38.15_suppl.4004