Taken together, the data suggest that higher doses of ADI-PEG20 than the OBD may be needed in certain ASS-negative patients for response and patients who benefit have tumours which are negative for ASS expression.
Negative baseline ASS was also associated with longer PFS, P=0.025 (log-rank test); the median time to progression for ASS− patients was 3.6 months (95% CI: 1.6 12.7) compared with 1.8 months (95% CI: 0.7 3.4) for ASS+ patients.
One patient was ASS negative by immunohistochemical staining but qPCR value of 0.09 for ASS and failed to respond.
Interestingly, two patients who were ASS negative by immunohistochemistry and RT PCR at the start of therapy had a response to ADI-PEG20.
In contrast, of seven patients who were ASS negative and had doses <320 IU m−, no partial responses were observed and only two had stable disease/minor response, P=0.08 (Fisher's exact test).
In this regard, we plan a follow-up study in which only advanced melanoma patients whose tumours are ASS negative will be treated with ADI-PEG20 at 320 IU m−.
Interestingly, of the 10 patients who received a dose of 320 IU m− and were ASS negative, 4 (40%) had a partial response and 3 had stable disease for a CBR of 70%, as well as prolonged survival compared with ASS+ patients.
This study determined the prevalence and pattern of intestinal parasites among HIV positive and negative individuals to asses if trend of occurrence was evident.
