B-cell NHL: phase 1/2 results with fenretinide + rituximab

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Takeaway

  • In patients with B-cell non-Hodgkin lymphoma (B-NHL), fenretinide + rituximab (Rituxan) delivered moderate, but durable response with encouraging tolerability.

Why this matters

  • Fenretinide has demonstrated anti-tumor action in preclinical studies.

Study design

  • Phase 1/2 study of fenretinide + rituximab in 32 patients with B-NHLs.
  • In the phase 1 study, fenretinide was initiated at the maximal dose of 900 mg/m2; dose was reduced to 700 mg/m2 pending dose-limiting toxicities.
  • In the phase 2 study, patient received fenretinide at the dose from phase 1 + rituximab 375 mg/m2.
  • De-escalation design in cohorts of 6 patients starting at the maximal dose of 900 mg/mby mouth twice-daily, on days 1-5 followed by a 2-d drug holiday.
  • Funding: National Institutes of Health.

Key results

  • 7 patients treated in phase 1; 25 patients treated in phase 2.
  • In the phase 2 study:

     —    selected dose: fenretinide 900 mg/m2,

     —    24% of patients responded (all in phase 2),

     —    47 mo median duration of response,
     —    56% disease-control rate,
     —    91.7% experienced tumor reduction,
     —    8 mo median PFS; median OS was not reached,
     —    most common grade ≥3 adverse events: rash (3 patients), neutropenia (3 patients).

 

 Limitations

  •  Limited sample size.