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Excerpt from a Needs Assessment for Colorectal Cancer

GAP #3: Primary care physicians may lack familiarity with current colorectal cancer treatment protocols and emerging therapies.

Although treatment of colorectal cancer (CRC) is generally the responsibility of a specialist, a recent survey of primary care physicians revealed that more than 50% of primary care physicians were involved in determining the treatment preferences of cancer patients and deciding on the use of surgery.¹ PCPs need to help patients through the associated cosmetic, psychological and sexual issues associated with painful and deforming surgeries. In addition, primary care physicians often manage symptoms and comorbid conditions for cancer patients.  Therefore, primary care physicians need to frequently update their knowledge of the treatment protocols available, including emerging new therapies, in order to provide optimum care and improve patient outcomes.

For patients with stage I CRC, surgical intervention is sufficient and adjuvant therapy is not required.¹ Whether patients with stage II CRC should receive adjuvant therapy is controversial, and treatment decisions should incorporate discussions with the patient about prognosis, efficacy and possible toxicities associated with treatment. Patients with stage III CRC should receive 6 months of adjuvant chemotherapy. For patients with metastatic CRC, different chemotherapy protocols of neoadjuvant or adjuvant therapy are considered. One of the targeted therapies, bevacizumab, cetuximab, or panitumumab, may be added to a chemotherapy regimen for patients with metastatic CRC. Use of these targeted agents has resulted in improved 2-year survival rates in clinical trials.²

Primary care physicians should be aware of side effects associated with the targeted therapies. Bevacizumab is known to interfere with wound healing, and elderly patients receiving bevacizumab have an increased risk of stroke and other arterial events.³ Another rare, but important, side effect of bevacizumab is gastrointestinal perforation.  Skin toxicity is a side effect of both cetuximab and panitumumab therapy, and the presence and severity of skin rash has been shown to be predictive of increased response and survival.^4,5

Several novel targeted agents are currently in phase III clinical trials for patients with metastatic CRC.  Early results from the CORRECT trial for regorafenib, an oral multikinase inhibitor, indicate that regorafenib may increase overall survival compared to placebo in patients that had progressed after all approved standard therapies.⁶  Aflibercept, an inhibitor of angiogenesis, significantly improved overall survival in combination with FOLFIRI as second-line treatment in the VELOUR study.⁷ Perifosine, an AKT inhibitor is currently in phase III trials in combination with capecitabine and results are expected soon.⁸

While not prescribing the medications, an awareness of the growing number of options for treating advanced disease presently available or in clinical trials and the day to day management of the associated adverse events and co-morbidities is an increasingly important role of primary care providers.

References

1. Klabunde CN, Ambs A, Keating NL, He Y, Doucette WR, Tisnado D, Clauser S, KahnKL. The role of primary care physicians in cancer care. J Gen Intern Med. 2009;24(9):1029-36.

2. Chu E. An update on the current and emerging targeted agents in metastatic colorectal cancer. Clin Colorectal Cancer. 2012 Mar;11(1):1-13.

3. Package Insert. AVASTIN® (bevacizumab). South San Francisco, CA: Genentech, Inc.; 2009. Available at: http://www.accessdata.fda.gov/drugsatfda_docs/label/2009/125085s0168lbl.pdf. Accessed March 18, 2012.

4. Berlin J, Van Cutsem E, Peeters M, et al. Predictive value of skin toxicity severity for response to panitumumab in patients with metastatic colorectal cancer (mCRC): A pooled analysis of five clinical trials [abstract]. J Clin Oncol. 2007;25 (June 20 suppl):4134.

5. Jonker DJ, O'Callaghan CJ, Karapetis CS, et al. Cetuximab for the treatment of colorectal cancer. N Engl J Med 2007;357:2040-2048.

6. Grothey A, Sobrero AF, Siena S, et al. Results of a phase III randomized, double-blind, placebo-controlled, multicenter trial (CORRECT) of regorafenib plus best supportive care (BSC) versus placebo plus BSC in patients (pts) with metastatic colorectal cancer (mRC) who have progressed after standard therapies[abstract]. J Clin Oncol. 2012;30 (suppl 4):LBA385.

7. Tabernero J. Results from VELOUR, a phase III study of aflibercept (A) versus placebo (pbo) in combination with FOLFIRI for the treatment of patients (pt) with previously treated metastatic colorectal cancer (MCRC). Program and abstracts of the 2011 European Multidisciplinary Cancer Congress; September 23-27, 2011; Stockholm, Sweden. Abstract LBA6.

8. Perifosine Plus Capecitabine Versus Placebo Plus Capecitabine in Patients With Refractory Advanced Colorectal Cancer (X-PECT).  NCT01097018.  Clinicaltrials.gov Web site. Accessed March 18, 2012.

Additional samples available upon request.