Diffusion of Docetaxel in Metastatic Prostate Cancer
Diffusion of Docetaxel in Metastatic Prostate Cancer
Background Diffusion of new cancer treatments can be both inefficient and incomplete. The uptake of new treatments over time (diffusion) has not been well studied. We analyzed the diffusion of docetaxel in metastatic prostate cancer.
Methods We identified metastatic prostate cancer patients diagnosed from 1995 to 2007 using the Surveillance, Epidemiology, and End Results Program (SEER)–Medicare database. Medicare claims through 2008 were analyzed. We assessed cumulative incidence of docetaxel by socioeconomic, demographic, and comorbidity variables, and compared diffusion patterns to landmark events including release of phase III results and FDA approval dates. We compared docetaxel diffusion patterns in prostate cancer to those in metastatic breast, lung, ovarian, and gastric cancers. To model docetaxel use over time, we used the classic "mixed influence" deterministic diffusion model. All statistical tests were two-sided.
Results We identified 6561 metastatic prostate cancer patients; 1350 subsequently received chemotherapy. Among patients who received chemotherapy, docetaxel use was 95% by 2008. Docetaxel uptake was statistically significantly slower (P < .01) for patients older than 65 years, blacks, patients in lower income areas, and those who experienced poverty. Eighty percent of docetaxel diffusion occurred prior to the May, 2004 release of phase III results showing superiority of docetaxel over standard-of-care. The maximum increase in the rate of use of docetaxel occurred nearly simultaneously for prostate cancer as for all other cancers combined (in 2000).
Conclusion Efforts to increase the diffusion of treatments with proven survival benefits among disadvantaged populations could lead to cancer population survival gains. Docetaxel diffusion mostly preceded phase III evidence for its efficacy in castration-resistant prostate cancer, and appeared to be a cancer-wide—rather than a disease-specific—phenomenon. Diffusion prior to definitive evidence indicates the prevalence of off-label chemotherapy use.
The diffusion of new health care innovations can be inefficient: sometimes treatments with proven benefit permeate slowly through the treatment community, while in other instances, uptake of new drugs occurs prior to definitive evidence. For such reasons, the study of diffusion has been a major focus of agencies within the National Institutes of Health (NIH). The past several decades have witnessed the introduction of multiple new cancer therapies. The appropriate and rapid adoption of proven new cancer treatments could impact population survival.
Diffusion is the transmission of a new innovation over time within a social system and is driven by perceptions of the innovation, characteristics of adopters, and contextual factors. Perceptions of an innovation pertain to (often qualitative) assessments of the risks and benefits of the new innovation. Presentation of efficacy findings for a new drug at a scientific conference or in a journal may influence the perception of new treatment benefits. Drugs with clearly positive benefit/risk ratios may be taken up immediately into clinical practice. One question is whether adoption follows definitive evidence of a new treatment in a phase III study. Patient characteristics may also influence patterns of chemotherapy use. For instance, older lymphoma and ovarian cancer patients are less likely to receive chemotherapy.
Patients with metastatic prostate cancer typically receive androgen deprivation therapy (ADT), with response durations of 18 to 24 months. For patients with castration-resistant prostate cancer (CRPC), standard therapy was mitoxantrone combined with prednisone following positive clinical trials in the 1990s, showing that mitoxantrone provided palliative relief but no survival benefit. Docetaxel (Taxotere, Sanofi-Aventis) received US Food and Drug Administration (FDA) approval for treatment of advanced breast and lung cancers in the late 1990s. Thereafter in 2004, docetaxel was shown to provide both pain relief and improved survival in CRPC, reducing the risk of death by about 20%, and, with concurrent FDA approval, became new standard care. In this analysis, we hypothesized that docetaxel uptake followed definitive evidence of docetaxel efficacy in a phase III trial, and that diffusion was slower for disadvantaged patient populations.
Abstract and Introduction
Abstract
Background Diffusion of new cancer treatments can be both inefficient and incomplete. The uptake of new treatments over time (diffusion) has not been well studied. We analyzed the diffusion of docetaxel in metastatic prostate cancer.
Methods We identified metastatic prostate cancer patients diagnosed from 1995 to 2007 using the Surveillance, Epidemiology, and End Results Program (SEER)–Medicare database. Medicare claims through 2008 were analyzed. We assessed cumulative incidence of docetaxel by socioeconomic, demographic, and comorbidity variables, and compared diffusion patterns to landmark events including release of phase III results and FDA approval dates. We compared docetaxel diffusion patterns in prostate cancer to those in metastatic breast, lung, ovarian, and gastric cancers. To model docetaxel use over time, we used the classic "mixed influence" deterministic diffusion model. All statistical tests were two-sided.
Results We identified 6561 metastatic prostate cancer patients; 1350 subsequently received chemotherapy. Among patients who received chemotherapy, docetaxel use was 95% by 2008. Docetaxel uptake was statistically significantly slower (P < .01) for patients older than 65 years, blacks, patients in lower income areas, and those who experienced poverty. Eighty percent of docetaxel diffusion occurred prior to the May, 2004 release of phase III results showing superiority of docetaxel over standard-of-care. The maximum increase in the rate of use of docetaxel occurred nearly simultaneously for prostate cancer as for all other cancers combined (in 2000).
Conclusion Efforts to increase the diffusion of treatments with proven survival benefits among disadvantaged populations could lead to cancer population survival gains. Docetaxel diffusion mostly preceded phase III evidence for its efficacy in castration-resistant prostate cancer, and appeared to be a cancer-wide—rather than a disease-specific—phenomenon. Diffusion prior to definitive evidence indicates the prevalence of off-label chemotherapy use.
Introduction
The diffusion of new health care innovations can be inefficient: sometimes treatments with proven benefit permeate slowly through the treatment community, while in other instances, uptake of new drugs occurs prior to definitive evidence. For such reasons, the study of diffusion has been a major focus of agencies within the National Institutes of Health (NIH). The past several decades have witnessed the introduction of multiple new cancer therapies. The appropriate and rapid adoption of proven new cancer treatments could impact population survival.
Diffusion is the transmission of a new innovation over time within a social system and is driven by perceptions of the innovation, characteristics of adopters, and contextual factors. Perceptions of an innovation pertain to (often qualitative) assessments of the risks and benefits of the new innovation. Presentation of efficacy findings for a new drug at a scientific conference or in a journal may influence the perception of new treatment benefits. Drugs with clearly positive benefit/risk ratios may be taken up immediately into clinical practice. One question is whether adoption follows definitive evidence of a new treatment in a phase III study. Patient characteristics may also influence patterns of chemotherapy use. For instance, older lymphoma and ovarian cancer patients are less likely to receive chemotherapy.
Patients with metastatic prostate cancer typically receive androgen deprivation therapy (ADT), with response durations of 18 to 24 months. For patients with castration-resistant prostate cancer (CRPC), standard therapy was mitoxantrone combined with prednisone following positive clinical trials in the 1990s, showing that mitoxantrone provided palliative relief but no survival benefit. Docetaxel (Taxotere, Sanofi-Aventis) received US Food and Drug Administration (FDA) approval for treatment of advanced breast and lung cancers in the late 1990s. Thereafter in 2004, docetaxel was shown to provide both pain relief and improved survival in CRPC, reducing the risk of death by about 20%, and, with concurrent FDA approval, became new standard care. In this analysis, we hypothesized that docetaxel uptake followed definitive evidence of docetaxel efficacy in a phase III trial, and that diffusion was slower for disadvantaged patient populations.
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