Medicine (St Vincent's) - Theses

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Type: Doctorate × Author: Dowling, Anthony John ×

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    The clinical utility of serum tumour markers prostate specific antigen and carcinoembryonic antigen in evaluating the effectiveness of chemotherapy for advanced prostate and colorectal cancers
    Dowling, Anthony John ( 2014)
    Palliative chemotherapy for the treatment of metastatic castrate resistant prostate cancer (mCRPC) and metastatic colorectal cancer (mCRC) should only continue if the patient is deriving some benefit. Clinicians assess benefit using a variety of methods. The tumour markers, prostate specific antigen (PSA) and carcinoembryonic antigen (CEA) can be used as part of this assessment. I explored the clinical utility of using PSA and CEA to guide decisions on palliative chemotherapy for mCRPC and mCRC patients. I evaluated if falling levels of PSA predicted for a palliative response (decreasing pain and/or pain medication), and improved survival in 161 patients with mCRPC treated with mitoxantrone and prednisone in a randomised clinical trial. I also performed a phase IV analysis of 133 patients treated at Princess Margaret Hospital, Toronto, Canada to see how they compared with the clinical trial. Also, a retrospective cohort of 142 patients with mCRC treated with oxaliplatin-based chemotherapy at St Vincent’s Hospital Melbourne were evaluated to see if falling levels of CEA predicted survival and shrinkage of secondaries. A PSA response of 50% occurred in 34% of patients in the mitoxantrone and prednisone arm of the study and in 28% of the post trial cohort (P=0.36) A PSA response of 50% is predictive of a palliative response, although the strength of the association was relatively weak (phi coefficient =0.28, P = 0.001). The positive predictive value of a PSA response for a palliative response was 53%. Using a landmark analysis, PSA responders lived longer (P=0.0004). A CEA response of 50% occurred in 74% of the mCRC patients. Using a landmark analysis, CEA responders lived longer (P<0.0001). CEA response did correlate with radiological responses. Seventy per cent of the CEA responders had a complete or partial response on computed tomography (CT) scanning, but 42% of the CEA responders also had stable disease, and 36% of the CEA non-responders had a partial response. Both PSA and CEA responses yield useful adjunctive clinical information and should be part of the clinical assessment of the palliative benefit from chemotherapy for mCRPC and mCRC.