Maurie Markman, MD
One of the most important activities of a medically trained oncologist is organizing the administration of antineoplastic drug therapy. While certain medications are delivered orally, including many hormonal treatments and an increasing number of molecularly targeted therapeutics, systemic drug delivery has for decades served as the backbone of most medically oriented oncology practices.
Patients may receive treatment in an individual physician office, an infusion center run by a group, or an outpatient or inpatient hospital setting. The nurses, technicians, pharmacists, and other personnel who work together may be employees of the physician’s practice, a hospital, or an independent infusion center.
Although the drugs, infusion times, and schedules may change, the delivery of antineoplastic therapy via the intravenous route is a long-standing, critical, and well-coordinated component of oncology practice.
Oncology care providers do not seem to have any trouble adapting to change in this area. But what happens when a novel treatment strategy is introduced into the oncology arena that challenges this traditional drug infusion paradigm? Clearly, in the research setting, some oncologists may enthusiastically elect to participate in individual trials while others (as is the case with research in general) may decline this opportunity.
Ovarian Cancer Example
How, then, can research advances be translated into broad clinical practice? Specifically, what is the appropriate response by oncologists when phase III randomized trial data reveal an improvement in a highly clinically relevant outcome associated with a truly new approach to cancer management that is not based on intravenous infusion or an oral approach? Under these circumstances, should all individual oncology practices learn how to effectively administer such therapy?
Consider the experience with intraperitoneal cisplatin- based chemotherapy delivery in the management of small volume residual advanced ovarian cancer following primary surgical cytoreduction.1,2
Three large, well-designed phase III randomized trials conducted by a National Cancer Institutecooperative group have revealed that use of this route of administration improves overall survival in this clinical setting compared with intravenous cisplatin.1
However, rather extensive data have documented the unquestionably disconcerting fact that only a small fraction of women who are potential candidates for this strategy are actually treated with this solidly evidence-based approach.2
The critical question is, why?
While a number of possible reasons can be advanced (including the toxicity of cisplatin compared with carboplatin), it is reasonable to suggest that the lack of familiarity and limited experience with this strategy as well as a critical absence of necessary infrastructure within a given practice setting to administer therapy by this route plays a major role in the most unfortunate decision to not offer patients a treatment that has been shown to potentially improve survival outcomes.
Further, it may be the feeling of some (or many) oncologists that there is not sufficient financial compensation for the additional time, effort, and training required to successfully deliver chemotherapy by the intraperitoneal route.
Recent Advances May Face Barriers It is interesting to note that while the issues surrounding the administration of intraperitoneal chemotherapy have been evident for several decades, there are more recent additions to the cancer management armamentarium where similar questions regarding experience as well as the required training and effort will likely weigh heavily in the decision by an individual oncologist or group to employ the novel approach in routine oncologic practice.
Talimogene laherparepvec is a novel herpes simplex virus oncologic immunotherapy that has been shown to favorably impact time to disease progression and improve survival in a highly select group of patients with unresected stage IIIB, IIIC, or IV advanced melanoma.3
The treatment requires intralesional injection of this novel product.
How will this antineoplastic approach actually be employed in routine practice, recognizing that the clinical indications are limited and alternative strategies such as systemic immunotherapy may be available? Will oncologists embrace the strategy, based on the phase III trial data and regulatory approval and attempt to employ the approach in their practices, or will they send patients who may benefit to a regional or academic center where there may be more experience, or perhaps even to another local practice where the approach is being employed? Or will oncologists simply elect to ignore the existing data, similar to what appears to be the situation with intraperitoneal chemotherapy for ovarian cancer, due to similar concerns about the time, effort, experience required, and limited financial compensation?