Clinical trials are used to both demonstrate that a drug or treatment has efficacy (extends life or improves the quality of life). They also are used as the vehicle to obtain approval from the governmental body responsible for monitoring and approving their use. How the trial is set up will directly dictate the eventual approved label (the approved dose as well as any additional drugs or treatments to be administered along side the investigational drug, etc.). This doesn’t necessarily mean that the label is actually the best option for use as other untested doses or co-administered drugs could still be better than what was tested.
A good example of this is the randomized studies that have shown improved survival with the combination of docetaxel (D) and prednisone in men with metastatic castration-resistant prostate cancer (mCRPC). Some researchers have retrospectively investigated whether the co-administration of low-dose glucocorticoids (like prednisone) can offer any additional clinical benefits.
In the study the researchers evaluated the records from 358 men with metastatic castration-resistant prostate cancer treated consecutively with either docetaxel (75mg/m(2) every 3 weeks (n = 124)) or docetaxel along with prednisolone (P) (10mg daily (n = 234)). Of these, 15 men treated with glucocorticoids at initiation of D were excluded.
The researchers evaluated any grade of peripheral edema grade greater than or equal to 2, sensory neuropathy grade greater than or equal to 3, and non-hematological toxicity. Background clinical data, rates of toxicity, hospital admissions, dose reductions, and post-docetaxel treatments were also analyzed. They also evaluated progression-free and overall survival.
They found that the men treated with docetaxel alone had a higher incidence of peripheral edema (32% vs. 15%, P<0.001) and grade 3 non-hematological toxicity (56% vs. 43%, P = 0.022). Men treated with docetaxel alone were also more frequently hospitalized (53% vs. 41%, P = 0.035), mainly owing to a higher incidence of febrile neutropenia in this group (25% vs. 10%, P<0.001).
The prednisone did not influence progression-free survival or overall survival when adjusting for baseline levels of hemoglobin, alkaline phosphatase, lactate dehydrogenase, prostate-specific antigen, and Eastern Cooperative Oncology Group performance status.
They concluded that the co-administration of low-dose prednisone with chemotherapy using docetaxel reduced the incidence of peripheral edema, grade 3 non-hematological toxicity, and the risk of being admitted to the hospital owing to febrile neutropenia during treatment. Adjusted survival analysis did not indicate that prednisone affected prognosis.
Urol. Oncol 2015 Aug 05;