Is hydrazine sulfate an effective and safe treatment for cancer, and should it be used outside of a clinical trial?

Hydrazine Sulfate for Cancer Treatment

Hydrazine sulfate should not be used for cancer treatment outside of clinical trials, as high-quality evidence demonstrates it provides no benefit and may worsen outcomes. 1

Guideline-Based Recommendations

Primary Recommendation

The most authoritative guideline explicitly states that hydrazine sulfate is not an appetite stimulant (Level of Evidence: A) and lacks sufficient evidence to support its use as a cytokine inhibitor for cancer cachexia. 1 The 2020 ASCO Guideline on Management of Cancer Cachexia specifically lists hydrazine sulfate among "other pharmacologic agents" that have been evaluated but currently have insufficient evidence of benefit. 1

Evidence Quality Assessment

The French National Federation of Cancer Centers (FNCLCC) guidelines from 2003 provided Level A evidence (the highest level, defined as "high-standard meta-analysis or several high-standard randomized clinical trials which give consistent results") that hydrazine sulfate is not an appetite stimulant. 1 This represents the strongest possible evidence classification in their framework.

Clinical Trial Evidence

Negative Randomized Controlled Trial

The most rigorous study was a randomized, placebo-controlled trial in 127 patients with metastatic colorectal cancer that demonstrated:

• Trends toward poorer survival in the hydrazine sulfate group 2
• Trends toward poorer quality of life in the hydrazine sulfate group 2
• No significant differences in anorexia or weight loss between groups 2
• The trial explicitly concluded it "failed to demonstrate any benefit for hydrazine sulfate" 2

Contradictory Uncontrolled Studies

While some older, uncontrolled case series from the 1970s-1990s reported subjective improvements in 42-70% of patients, these studies lacked placebo controls and randomization. 3, 4, 5, 6 The subjective nature of these endpoints (appetite, strength, performance status) makes them highly susceptible to placebo effects, which is why the subsequent randomized controlled trial is definitive. 2

Clinical Decision Algorithm

When patients inquire about hydrazine sulfate:

1. Inform them that high-quality randomized evidence shows no benefit and possible harm 2

2. If cachexia/anorexia is the concern, offer evidence-based alternatives:

   • Megestrol acetate (minimum 160 mg daily) for appetite stimulation and weight gain 1
   • Corticosteroids for short-term appetite improvement in patients with life expectancy of weeks to months 1
   • Consider olanzapine as an emerging option requiring further study 1

3. If the patient insists on experimental approaches, direct them toward appropriate clinical trials rather than unproven agents 1

Important Caveats

The discrepancy between older case series and the randomized trial highlights a critical principle: uncontrolled observations in cancer patients are unreliable due to the natural variability of disease, concurrent treatments, and powerful placebo effects. 2 The fact that the only placebo-controlled trial showed trends toward harm rather than benefit is particularly concerning. 2

Off-label use in oncology is common and sometimes appropriate when standard therapies have failed, but this applies to agents with at least some supporting evidence. 7 Hydrazine sulfate does not meet this threshold given the negative randomized trial data. 2