To determine if fatigue or cognitive dysfunction is caused by enzalutamide, a clinician suggests a practical approach called the "Stevens Maneuver." The patient stops the drug for two weeks. If symptoms don't improve, the cause is likely something else. If they do improve, the drug is the culprit, and it can often be resumed at a lower dose.
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The failure of an adjuvant trial for the TKI pazopanib was likely caused by a protocol change that reduced the dose to manage transaminitis. While well-intentioned to improve tolerability and adherence, the lower dose was sub-therapeutic. This serves as a critical lesson that managing side effects by compromising dose can nullify a drug's potential efficacy.
Doctors are often trained to interpret symptoms arising after stopping psychiatric medication as a relapse of the original condition. However, these are frequently withdrawal symptoms. This common misdiagnosis leads to a cycle of re-prescription and prevents proper discontinuation support.
Long-term, high-dose GLP-1 use leads to diminishing returns and significant muscle loss. A more effective strategy is using micro-doses in 90-day cycles, paired with nutritional coaching. This approach uses the drug as a temporary tool to eliminate carb cravings and establish lasting dietary habits.
Patients can successfully request hormone tests by describing subjective declines in energy, focus, or athletic performance compared to their past selves. This provides the necessary clinical justification for the lab work without requiring a pre-existing diagnosis.
Instead of medicating or ignoring symptoms like fatigue or mood swings, view them as your body's way of signaling an underlying issue. By treating symptoms as messages, you can focus on the root cause (like glucose spikes), which makes the 'messages' disappear.
Many people use substances to treat anxiety or depression, not realizing the substance itself causes a dopamine deficit that mimics those conditions. Abstaining for four weeks allows the brain to reset its reward pathways and restore natural dopamine production, often resolving the symptoms entirely.
The enzalutamide arms saw discontinuation rates of 20-25% due to adverse events. This high rate reflects a different risk calculation for patients who feel healthy and are asymptomatic. Unlike in advanced disease where patients tolerate more toxicity, this population has a very low threshold for side effects, making early intervention a significant trade-off.
A critical distinction exists between a clinical adverse event (AE) and its impact on a patient's quality of life (QOL). For example, a drop in platelet count is a reportable AE, but the patient may be asymptomatic and feel fine. This highlights the need to look beyond toxicity tables to understand the true patient experience.
The common practice of switching from one ARPI to another upon disease progression is now considered ineffective for most patients. With the advent of proven alternatives like chemotherapy and lutetium, using an "ARPI switch" as the sole control arm in clinical trials is no longer ethically or scientifically sound.
Despite showing massive weight loss, new obesity drugs from Eli Lilly and others have high discontinuation rates due to side effects. This suggests the industry's singular focus on efficacy may be hitting diminishing returns, opening a new competitive front based on better patient tolerance and adherence.
