Soft Tissue Sarcoma with Jonathan C. Trent, MD, PhD and Shreyaskumar R. Patel, MD: Case 2 - Episode 6
What are the main indications for dose reduction in patients on trabectedin?
If you go back to the phase III registrational clinical trial that just recently got published in theJournal of Clinical Oncology, the dose reduction guidelines were left to the treating physician and the investigators in some ways. The drug isn’t very well tolerated. The dose limiting toxicities again can be hematologic or non-hematologic. The hematologic toxicities are neutropenia or neutropenic fever, but an occasional patient can even see some severe thrombocytopenia. A lot depends upon how heavily they have been treated prior to initiation of Yondelis. So the dose reduction for hematologic toxicities is again left to the discretion of the treating physician.
There are patients who will have a transient drop in their platelet count to 20,000 but recover quickly. Even if they needed a platelet transfusion, as long as there were no consequences of that, one could maintain the same dose to get the maximum benefit. On the other hand, if the clinical judgment suggested that this is a fragile patient and the risks were high, you could dose reduce by one level from 1.5 mg down to 1.2 mg, for example. Similarly for febrile neutropenia, as well.
If the episode was uncomplicated, it’s the clinician’s decision as to whether dose reduction in that given patient is absolutely mandatory or can the patient maintain the same dose to get the maximum benefit. The non-hematologic toxicities are a little different, I think the liver toxicities in particular. The transaminitis that patients could get can create some life-threatening situations. Liver toxicity in terms of transaminitis, elevated bilirubins or an obstructed pattern with elevated alkaline phosphatase is taken a lot more seriously, I think, because that clearly can have some life-threatening implications for that given patient.
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 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.