Personalized Treatment Planning: A Pharmacist’s Perspective

JS is a 62-year-old female diagnosed with a stage IIB (T2, N1, M0), estrogen receptor/progesterone receptor–negative, HER2-negative invasive ductal carcinoma of the breast 18 months ago and treated with bilateral mastectomy followed by adjuvant docetaxel and cyclophosphamide (TC). Recently, she felt an enlarged supraclavicular lymph node that was subsequently biopsied and showed recurrence of her disease. She presents today for discussion regarding selection of chemotherapy in the recurrent/metastatic setting.

Scenarios like the one above are a daily occurrence in cancer centers around the country and around the world. These situations are fraught with emotion and anxiety as patients are informed, most commonly, that their disease is no longer curable. In these moments, patients and their families seek assurance that as an oncology healthcare team, we are evaluating every reasonable option and are deciding upon a treatment plan that offers the greatest hope for the patient to live as long as possible and with the greatest quality of life. Throughout this series on Conquering the Cancer Care Continuum, we have focused on the multidisciplinary nature of modern oncology medicine and the role that highly trained and specialized providers from a variety of disciplines (medicine, pharmacy, and nursing) can play in managing the patient with cancer. Here, we will discuss the role of the clinical oncology pharmacist in consultation with the oncology team in defining the patient’s treatment plan.

Chemotherapy Planning
For patients such as JS, the treatment plan that will ultimately affect future clinical decision making with regard to drug therapy begins with the determination of the initial adjuvant chemotherapy regimen. The reader will have recognized that because JS has triple-negative breast cancer, there is no indication for endocrine therapy or HER2-targeted drugs such as trastuzumab. While targeted therapies may not play a role for JS, selection of adjuvant chemotherapy still requires an educated decision on behalf of the oncology team. The National Comprehensive Cancer Network (NCCN) clinical practice guidelines for breast cancer offer consideration of 4 category 1 recommendations for patients such as JS. These include TAC (docetaxel, doxorubicin, and cyclophosphamide), AC (doxorubicin and cyclophosphamide) given in the conventional every-3-week manner or in a dose-dense every-2-week option, and TC.1 For common malignancies such as breast cancer, each provider or cancer center likely has adopted 1 (or more) of these treatment standards for use in patients such as JS. Based on results of a phase 3 clinical trial in which TC was demonstrated to be superior to AC with regard to disease-free survival and overall survival, we selected TC for JS.^2,3 In addition to improvements in efficacy, the anthracycline-sparing nature of this regimen makes it a reasonable option for patients who have a history of heart disease or are found to have an unacceptable left ventricular ejection fraction by echocardiogram or multigated acquisition scan. However, our treatment plan for JS is not yet complete! Let’s evaluate ways in which the clinical oncology pharmacist can contribute to the success of the healthcare team and ultimately patient outcomes in the setting of drug utilization.

First, in many cancer centers, the oncology pharmacist is responsible for the development of written chemotherapy protocols. On first glance, this action may be regarded as a technical task that could be delegated to nonhealthcare-trained paraprofessionals. However, the American Society of Clinical Oncology (ASCO) in conjunction with the Oncology Nursing Society (ONS) have placed great importance on this activity. In their Standards for Safe Chemotherapy Administration, ASCO-ONS recommend that these protocols, or treatment plans, be preprinted, standardized, and completed by an appropriate oncology provider. Furthermore, they recommend that a rationale and justification be provided, complete with appropriate references, if orders deviate from standard protocols.⁴ Each step of this process is guided by the intent to ensure safe handling and administration of all cytotoxic and biologic drugs used in the cancer center. The role of the oncology pharmacist in contributing to and supporting, via the medical literature, both standard and nonstandard chemotherapy prescribing relates additionally to the Joint Commission of Pharmacy Practitioners Vision of Pharmacy Practice. This collaboration composed of representatives from many of the major professional pharmacy organizations has issued a vision statement that reads, “Pharmacists will be the health care professionals responsible for providing patient care that ensures optimal medication therapy outcomes.”⁵ Preparation of standard order sets for chemotherapy is one of several steps through which the oncology pharmacist is often involved in treatment planning for patients with cancer.

Next, it is important to recognize that most oncology pharmacists who practice in a clinical capacity have not only completed a doctor of pharmacy degree but also years of additional residency training and often board certification in oncology practice. This additional specialized training allows for the development of an expertise gained while training side by side with physician colleagues and validated via board exams similar to those taken by oncologists. As such, these pharmacy providers can have a much greater impact on the patient’s optimal medication therapy outcomes. In many centers, the clinical pharmacist rounds with the oncology team, sees and assesses patients with the oncologist, and provides recommendations for management in accord with accepted clinical practice guidelines and based upon an intense depth of knowledge of clinical trial results and the medical literature. These “advanced practice” pharmacists provide what may be regarded as a second opinion, without the patient traveling for a second opinion. Through this decision-making capacity, clinical pharmacists have an opportunity to contribute directly to the management of the cancer patient and provide an invaluable resource to the oncology healthcare team and, arguably, a marketable advantage to the cancer center.

When we consider the case of JS and her newly recurrent breast cancer, we see an opportunity for collaboration of providers (medicine, pharmacy, and nursing) to evaluate the best choice of therapies in the context of her response to and tolerance for adjuvant chemotherapy, her performance status at the time of this visit, and her goals for therapy moving forward. Because this is not meant to be a commentary on “how we treat breast cancer,” I will avoid the in-depth discussion that typically occurs but rather share a couple of examples of how clinical decision making might take place for a patient such as JS. For example, it is well established within the oncology literature that taxane-based therapies can induce peripheral neuropathy, some degree of which may be irreversible. If JS had experienced severe neuropathy or continued to suffer from this as a long-term consequence of her exposure to docetaxel, it would be entirely reasonable in the recurrent/metastatic setting to avoid other drugs known to have a similar toxicity profile (eg, nab-pac­litaxel). Likewise, if she had some degree of renal insufficiency, avoidance of platinum drugs, especially cisplatin, would represent an informed decision and, in essence, personalization of therapy for this patient. Certainly these decisions are made singularly by oncologists on a daily basis in centers without clinical pharmacists. However, when healthcare providers collaborate, the patient ultimately becomes the greatest beneficiary as barriers to therapy may be more likely to be prospectively identified and avoided, resulting in better patient outcomes.

Because it has been nearly 15 months since JS completed adjuvant TC chemotherapy, and her tolerance for that treatment regimen was outstanding, the oncology team presumes that she still has taxane-sensitive disease and elects to treat her with nab-paclitaxel. Note that while combination chemotherapy regimens may result in better efficacy, additional toxicity is also often observed. It is for this reason that the NCCN Guidelines offer both single agents and combinations of agents as appropriate first-line therapy for patients with recurrent/metastatic disease.¹

Supportive Care Planning
For patients with cancer, the focus predominantly becomes the selection of the best treatment for their disease. However, the supportive care needs of the patient cannot be overlooked and should also be considered integral to their well-being. A classic example of this is prophylaxis of chemotherapy-induced nausea and vomiting (CINV). Multiple studies have evaluated the functional impact and cost of care that arises as a result of CINV and found that patients who are poorly managed are more likely to experience an inability to eat and drink, to want to spend time with family and friends, and to maintain normal daily function. Furthermore, direct and indirect healthcare costs are also greater in this patient population.⁶ Appropriate identification of an individual’s risk factors for CINV, and evaluation of the treatment regimen based on Paul Hesketh’s well-regarded research related to the acute emetogenicity of these agents, should allow the oncology team to avoid this potential therapy pitfall and protect the patient’s quality of life.⁷
The TC regimen that JS was initially treated with is classified as moderately emetogenic and was managed appropriately with a 5-HT3 antagonist and dexamethasone. As a result, JS experienced only minimal nausea and no breakthrough emesis during or after each of her chemotherapy infusions. In the recurrent/metastatic setting, single-agent chemotherapy is often utilized, and many of these drugs have a low to moderate risk of CINV. While this simplifies the supportive care management of these patients, it is still a relevant concern that must not go overlooked. In many cancer centers, pharmacists play an integral role in evaluating, managing, and monitoring patients with regard to CINV. Not only does this improve patient outcomes, it also frees up the oncologist to manage other patient issues.

For JS, nab-paclitaxel is classified as low emetic risk, and she received no CINV prophylaxis. However, prescriptions were provided to her for ondansetron and promethazine to be used as needed at home. Routine monitoring during her ongoing nab-paclitaxel therapy has thus far revealed minimal requirement for antiemetic drugs. Overall, JS has tolerated this chemotherapy well, and recent scans demonstrate that her disease has responded. Nonetheless, the oncology team has already begun thinking about the next treatment option in an effort to stay 1 step ahead of her disease!

CINV is not the only supportive care problem that patients with cancer experience. Pain management, corticosteroid prophylaxis, bowel regimens, etc, are also very real medication-related issues that pharmacists may contribute to managing. Those interested in learning more should read previous issues of Conquering the Cancer Care Continuum as they relate to many of these other quality-of-life concerns.

Conclusion
It is evident that not all cancer centers employ pharmacists who function in the capacity discussed here. Having been trained in this manner and functioning in this role on a daily basis, I would be remiss to not advocate for the role of highly trained clinical oncology pharmacists whose participation in direct patient care enhances patient experiences within the cancer center and improves patient outcomes. Development of a treatment plan for patients with cancer is a hugely complex and utterly organic process that may change based upon a multitude of patient-specific factors whose identification is paramount to ensuring optimal outcomes. We have barely scratched the proverbial surface of this issue, but hopefully the ideas expressed here may provide some degree of insight into the thought process behind clinical decision making as it relates to developing treatment plans for patients with cancer.

References

1. National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines). Breast Cancer. Version 3.2013. www.nccn.org/professionals/physician_gls/f_guidelines.asp#breast. Accessed May 12, 2013.
2. Jones SE, Savin MA, Holmes FA, et al. Phase III trial comparing doxorubicin plus cyclophosphamide with docetaxel plus cyclophosphamide as adjuvant therapy for operable breast cancer. J Clin Oncol. 2006;24:5381-5387.
3. Jones S, Holmes FA, O’Shaughnessy J, et al. Docetaxel with cyclophosphamide is associated with an overall survival benefit compared with doxorubicin and cyclophosphamide: 7-year follow-up of US Oncology Research Trial 9735. J Clin Oncol. 2009;27:1177-1183.
4. American Society of Clinical Oncology/Oncology Nursing Society Chemotherapy Administration Safety Standards. www.asco.org/sites/www.asco.org/files/asco_ons_chemotherapysafetystandards_final.pdf. Accessed May 12, 2013.
5. Joint Commission of Pharmacy Practitioners Vision Statement. http://amcp.org/uploadedFiles/Horizontal_Navigation/Publications/Professional_Practice_Advisories/JCPP%20Vision%20for%20Pharmacy%20Practice.pdf. Accessed May 12, 2013.
6. Lindley CM, Hirsch JD, O’Neill CV, et al. Quality of life consequences of chemotherapy-induced emesis. Qual Life Res. 1992;1:331-340.
7. Hesketh PJ, Kris MG, Grunberg SM, et al. Proposal for classifying the acute emetogenicity of cancer chemotherapy. J Clin Oncol. 1997;15:103-109.