From Pharmacokinetics to Pharmacoeconomics: A Managed Care Look at Colorectal Cancer
J. Aubrey Waddell, PharmD, FAPhA, BCOP*
This issue of University of Tennessee Advanced Studies in Pharmacy summarizes the proceedings of a roundtable held in Scottsdale, Arizona, on March 30, 2007. The roundtable focused on clinical and economic aspects of current and emerging therapies for colorectal cancer (CRC), the fourth most prevalent cancer in the United States and the second leading cause of cancer death, after lung cancer, in this country.1
Featuring a distinguished faculty, the roundtable thematically progressed from the pharmacokinetics of monoclonal antibodies (mAbs) and other therapies to findings from several clinical trials evaluating these agents, the prevention and management of the complications of CRC treatment, and the optimization of care and case management for patients with CRC treated in a managed care setting. Members of the faculty included oncology pharmacists, professors of pharmacy, and chief pharmacy officers, directors, and managers.
As noted during the course of the roundtable, the treatment of CRC remains a challenge to all healthcare professionals. Although earlier detection and improved treatment have led to decreasing mortality rates over the past 15 years, CRC still accounts for 10% of all cancer-related deaths in the United States.2 Against this backdrop, it is clear that more efficacious therapies with diminished toxicity, as well as improved education and preventive strategies, are needed to reduce the incidence and mortality of CRC even further. This is particularly germane in managed care, which continues to assume a larger role in the overall healthcare system.
It is also clear that numerous advances in the adjuvant therapy of CRC in the past 20 years represent a major step forward.3 Among these advances is the addition of various agents to conventional chemotherapy with 5-fluorouracil (5-FU) plus leucovorin to enhance its activity against CRC.1 These agents include irinotecan, oxaliplatin, and several biologic agents or targeted therapies (eg, mAbs and small-molecule tyrosine kinase inhibitors) that inhibit tumor growth by interrupting growth factor-mediated signaling, thereby preventing cell survival and promoting apoptosis.4 Another agent used in combination with irinotecan, oxaliplatin, and/or biologic agents instead of 5-FU plus leucovorin is capecitabine, which is a pro-drug of 5-FU.
In his presentation on epidermal growth factor receptor inhibitors and other emerging CRC therapies, Lewis M. Iacovelli, PharmD, BS, BCOP, takes the first step in the thematic progression from pharmacokinetics to pharmacoeconomics. He reviews the role of the epidermal growth factor receptor (EGFR) in CRC and other human cancers, the properties of mAbs with anti-EGFR activity, and the effects of these mAbs on EGFR-positive tumors. He also compares chimeric versus human mAbs directed against EGFR, and notes that the latter may offer several advantages with respect to infusion times, infusion-related reactions, and the need for premedication and/or postinfusion observation. In addition, he discusses current research involving new targets, new techniques such as microarray screening, and antisense, gene, and vaccine therapy.
Robert J. Ignoffo, PharmD, follows with a review of recent and ongoing clinical trials evaluating various combinations of conventional chemotherapy (5-FU plus leucovorin) and several newer agents, including mAbs, in the adjuvant therapy of stage IIC and stage III CRC and the primary therapy of metastatic CRC. Although adjuvant therapy is not the standard of care for stage II CRC because surgery alone is curative in 75% of cases,5 Dr Ignoffo notes that some adjuvant regimens incorporating standard and newer agents are effective as first-, second-, and/or third-line therapy of stage III CRC and particularly metastatic CRC. As he points out, some new combination regimens, such as those involving a switch from bolus administration of 5-FU to continuous infusion and/or the addition of 1 or more of the newer agents, have emerged as new standards of care.
John M. Valgus, PharmD, BCOP, continues with a review of complications associated with conventional chemotherapy and the newer agents used to treat CRC. Noting that attention to prevention and early detection of these complications can significantly improve patient outcomes, he reviews strategies to manage treatment-induced toxicities such as diarrhea, hand-foot syndrome, peripheral neuropathies, rash, and infusion reactions.
Alan H. Heaton, PharmD, RPh, concludes the thematic progression from pharmacokinetics to pharmacoeconomics in his presentation on optimizing care and case management for patients with CRC. He describes several care management strategies to optimize cancer treatment and reviews the advantages of case management versus usual care in high-cost patients. He also discusses how changes in reimbursement affect both the selection of agents and the setting for delivery of care.
Each of the 4 articles presented in this issue of University of Tennessee Advanced Studies in Pharmacy features discussion highlights from the entire faculty, which also includes Dominic A. Solimando, Jr, RPh, MA, FASHP, FAPhA, BCOP, Dick Bullard, RPh, and Matthew R. (Rick) Rutledge, RPh, BCOP.
As suggested in the material presented here, advances in biotechnology have led to the development of new and targeted therapies that are already changing the care of patients with CRC. New and future therapies, along with the increasing role of managed care and its goal of ensuring the most appropriate use of medical and pharmacy services in the most cost-effective manner, underscore the integral role of the pharmacist in each component of CRC management to improve clinical and economic outcomes.
1. Terstriep S, Grothey A. First- and second-line therapy of metastatic colorectal cancer. Expert Rev Anticancer Ther. 2006;6:921-930.
2. American Cancer Society. Cancer Facts and Figures. Available at: www.cancer.org. Accessed April 15, 2007.
3. Nordman IC, Iyer S, Joshua AM, Clarke SJ. Advances in the adjuvant treatment of colorectal cancer. ANZ J Surg. 2006;76:373-380.
4. Booy EP, Johar D, Maddika S, et al. Monoclonal and bispecific antibodies as novel therapeutics. Arch Immunol Ther Exp (Warsz). 2006;54:85-101.
5. Benson AB 3rd. New approaches to the adjuvant therapy of colon cancer. Oncologist. 2006;11:973-980.
The content in this monograph was developed with the assistance of a staff medical writer. Each author had final approval of his/her article and all its contents.
*Associate Professor, University of Tennessee College of Pharmacy, Knoxville, Tennessee; Oncology Pharmacist, Blount Memorial Hospital, Maryville, Tennessee.
Address correspondence to: J. Aubrey Waddell, PharmD, FAPhA, BCOP, Pharmacy Department, Blount Memorial Hospital, 907 East Lamar Alexander Parkway, Maryville, TN 37804. E-mail: email@example.com.