Is it detrimental to have 2 Docetaxel (Taxotere) infusions prior to starting Lutetium-177 (Lu-177) therapy?

Prior Docetaxel Treatment Before LU-177 Therapy

Having two Docetaxel infusions prior to starting Lutetium-177 (LU-177) therapy is not detrimental and is actually consistent with the recommended treatment sequence according to current guidelines.

Evidence Supporting Prior Taxane Treatment Before LU-177

The NCCN Prostate Cancer Guidelines specifically recommend LU-177-PSMA-617 as a category 1 treatment option for patients who have been previously treated with both:

• Androgen receptor-directed therapy
• A taxane-based chemotherapy (such as Docetaxel) 1

This sequencing is supported by the VISION trial data, which showed significant improvements in overall survival (15.3 vs 11.3 months) and progression-free survival (8.7 vs 3.4 months) when LU-177-PSMA-617 was used after prior taxane therapy 1.

Rationale for the Treatment Sequence

The treatment sequence of Docetaxel followed by LU-177 is based on several factors:

1. Established efficacy pathway: LU-177-PSMA-617 has demonstrated efficacy specifically in the post-taxane setting
2. Different mechanisms of action: These therapies work through different mechanisms, allowing for sequential benefit
3. Potential radiosensitizing effects: Docetaxel has radiosensitizing properties that may enhance the effectiveness of subsequent radiopharmaceutical therapy 2

Safety Considerations

When administering LU-177 after Docetaxel, be aware of the following:

• Hematologic toxicity: Monitor for potential cumulative myelosuppression

  • Grade ≥3 adverse events are more common with LU-177, particularly anemia, thrombocytopenia, and lymphopenia 1, 3
  • Complete blood count should be monitored every 2-4 weeks after treatment 3

• Bone marrow reserve: Ensure adequate bone marrow function before initiating LU-177 therapy 3

  • Prior chemotherapy increases the risk for severe myelotoxicity 3

Alternative Approaches

While sequential therapy is standard, some research has explored concurrent administration:

• A phase I trial of Docetaxel plus LU-177-J591 demonstrated feasibility without dose-limiting toxicity, though this is not the standard approach 2

• More recently, a phase 2 study (UpFrontPSMA) explored LU-177-PSMA-617 followed by Docetaxel in hormone-sensitive prostate cancer, showing improved antitumor activity compared to Docetaxel alone 4

Practical Recommendations

1. Complete the planned Docetaxel course if clinically appropriate before transitioning to LU-177

2. Allow adequate recovery time between the completion of Docetaxel and initiation of LU-177 therapy to minimize overlapping toxicities

3. Perform baseline imaging with PSMA PET to confirm PSMA-positivity of lesions before initiating LU-177 therapy 1

4. Monitor closely for toxicities, particularly hematologic adverse events, during LU-177 treatment

In conclusion, prior Docetaxel treatment before LU-177 therapy is not only not detrimental but is actually the recommended treatment sequence according to current NCCN guidelines for patients with metastatic castration-resistant prostate cancer.