How effective are current treatments for DSRCT?

Question

Hello doctor,

I am a 24-year-old male diagnosed with metastatic desmoplastic small round cell tumor - EWS1 positive four years ago. I have been through different chemotherapies with varying success. Recently, I started Palbociclib 120 mg treatment and have seen improvements like reduced abdominal discomfort, increased appetite, and weight gain over the past month. We have a restaging imaging scheduled after cycle 2 in a month. I still feel fatigued and have trouble breathing when I exert myself, managing only about one block of walking before needing to rest. Otherwise, my condition is stable, and I can handle my daily activities independently.

In the past, I have undergone treatments like VAC (Vincristine, Adriamycin, and Cyclophosphamide), Thalidomide 100 mg, Cyclophosphamide 50 mg, Celecoxib 200 mg alternating with Etoposide, Temozolomide, Gemcitabine 1.4 gm and Docetaxel 100 mg, IE (Ifosfamide, Etoposide, and Mesna), Cabozantinib 40 mg, and Irinotecan.

Please help.

Thank you.

Answer 1

Hello,

Welcome to icliniq.com.

I understand your concern.

As we review your current situation, it is important to understand the specifics of your diagnosis. You have metastatic desmoplastic small round cell tumor (DSRCT), a challenging condition characterized by small round cell tumors. The tests have confirmed this diagnosis by showing a positive result for the EWSR1(Ewing sarcoma breakpoint region 1) gene translocation.

Unfortunately, despite the efforts with various treatments, it appears that the cancer has progressed through multiple stages. There are limitations to further treatment options after the initial VAC (Vincristine, Actinomycin D, and Cyclophosphamide) therapy. The main objectives of subsequent treatments are to slow the progression of the disease and alleviate your symptoms.

I am glad that you are experiencing some improvement with Palbociclib. It seems reasonable to continue with this medication for now and reevaluate your condition with imaging studies in a month for further follow-up.

However, there might be a possibility of disease progression. In such a scenario, I suggest salvage regimens. These include the following combinations:

Vinorelbine plus Cyclophosphamide plus Temsirolimus.
Vinorelbine plus Cyclophosphamide if Temsirolimus is not an option.
Another medication is Pazopanib, starting at 400 mg daily and adjusting to a twice-daily dosing schedule as tolerated.
In addition to these options, I suggest other regimens like Sunitinib, Dacarbazine, or a combination of Doxorubicin plus Dacarbazine (Doxylamine succinate 10 mg, Pyridoxine 10 mg, and folic acid 2.5 mg).

Also, given your negative immunohistochemistry (IHC) results for WT1 (Willams tumor 1) in the tumor samples, a scenario present in fewer than 10 percent of desmoplastic small round cell tumor (DSRCT) cases, I suggest validating the diagnosis of DSRCT through pathological confirmation by a pathologist and the Archer test (a molecular diagnostic tool used to detect gene fusions in cancer) to confirm EWSR1-WT1 fusion. This step would streamline potential future treatment avenues, particularly for enrollment in clinical trials.

In the event of progression on Palbociclib, I suggest to salvage chemotherapy regimens based on findings.

For instance, a combination of Vinorelbine (25 mg/m2 IV or into the vein on days 1 and 8), Cyclophosphamide (1200 mg/m2 IV on day 1), and Temsirolimus (15 mg/m2 IV on days 1, 8, and 15) yielded RECIST (response evaluation criteria in solid tumors) partial responses in all patients, with a median progression-free survival (PFS) of 8.5 months. Notably, one patient substituted IV Cyclophosphamide with oral cyclophosphamide at a dose of 25 mg/m2 daily.
Similarly, Vinorelbine (15-25 mg/m2 IV on days 1, 8, 15) combined with low-dose oral cyclophosphamide (25 mg/m2 daily) on a 28-day cycle demonstrated some RECIST partial responses in case reports of desmoplastic small round cell tumor (DSRCT).
Additionally, Pazopanib (400 mg-800 mg daily) resulted in complete response (CR) per RECIST criteria in 1 out of 29 patients, partial response (PR) in 1 out of 29 patients, and stable disease in 16 out of 29 (55 per) patients, with a median progression-free survival (PFS) of 5.6 months.

I hope this information is helpful to you.

Thank you.