Jonathan C. Trent, MD, PhD: Main Indication for Dose Reduction

What are the main indications for dose reduction in patients on trabectedin?

Dose reduction in patients on trabectedin is quite rare from my clinical practice. However, dose reductions may be indicated in patients that have grade 3, grade 4 toxicities, usually. These can include sepsis, these can include liver damage, these can be due to a systemic type of reaction such as anaphylaxis or even lower extremity edema that we see that can be quite profound. In addition to a dose reduction, there are ways to actively manage these grade 3 and 4 toxicities.

CASE: Soft-Tissue Sarcoma Case 2

Michael C is a 59-year-old social worker from Los Angeles California; his medical history is notable for obesity, COPD, and mild hypertension.

• In January of 2014, he presents to his PCP with complaints of right lower leg pain of several weeks’ duration
• Physical exam was unremarkable except for swelling of the lower right calf; x-ray of the affected leg was negative for fracture
• MRI scan of the lower right calf showed a 20 cm well defined lobular mass arising between the gastrocnemius and soleus
• Biopsy of the mass showed myxoid liposarcoma with round cell component. Patient underwent en bloc resection of the tumor following preoperative radiotherapy
• Gross examination showed the tumor to be 10 × 8 × 15 cm with gelatinous brownish appearance

In September of 2014, Michael returns for follow up and his CT scan shows a 4 cm posterior mediastinal mass, and a 6 cm perinephric mass suspicious for metastatic disease. He initiates treatment with anthracycline and ifosfamide chemotherapy (6 cycles) for recurrent disease and shows a partial response.

• In May of 2015, he returns for follow up with intermittent chest and lower back pain; CT scan is consistent with progression of the mediastinal and perinephric masses, and bone scan shows new lesions occurring in the L2 and L3 lumbar vertebrae
• At recurrence, liver and renal function and CBC are within normal limits, and his ECOG performance status is 1
• He received treatment with trabectedin (1.5 mg/m2 24-hr infusion given every 3 week)
• At the 2nd cycle he develops febrile neutropenia (ANC< 500 cells/mm3) requiring hospitalization
• The oncologist reduces his trabectedin dose to 1.2 mg/m2; he continues therapy
• Within 1 week, he shows clinical improvement and CT scan shows slight improvement