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PAI1: a useful biomarker for cervical cancer?
Newsdesk New progress in treatment of hormone-refractory prostate cancer Two studies have shown that docetaxelbased regimens yield better survival, pain control, and quality of life for patients with advanced hormonerefractory prostate cancer than do mitoxantrone-based regimens. “Our study, the largest ever undertaken for men with progressive hormone-refractory prostate cancer, showed that 3-weekly docetaxel gives a small but significant improvement in median survival compared to mitoxantrone—the standard palliative treatment”, explains Ian Tannock (Princess Margaret Hospital, Ontario, Canada), lead author of the first study (N Engl J Med 2004; 351: 1502–12). 1006 patients with advanced hormone-refractory prostate cancer were randomly assigned either docetaxel (weekly or every 3 weeks) or standard therapy (mitoxantrone every 3 weeks). All patients received prednisone twice daily. Patients receiving docetaxel every 3 weeks had better
3-month survival than did patients assigned mitoxantrone. There was also a reduction in pain and in concentrations of prostate-specific antigen. However, toxic effects were greater with docetaxel, and patients assigned it each week did no better than patients given standard treatment. In the second trial (N Engl J Med 2004; 351: 1513–20), Daniel Petrylak (Columbia University, Herbert Irving Comprehensive Cancer Center, NY, USA) and colleagues studied 770 patients with androgen-independent metastatic prostate cancer given docetaxel plus estramustine or mitoxantrone plus prednisone. Patients in the docetaxel group had better survival than those in other groups (17·5 months vs 15·6 months). This benefit was also associated with reduced PSA concentrations and improved progression-free survival. “These are extremely important studies”, says William Dahut (National
Cancer Institute, MD, USA), “because this is the first time any treatment has been shown to prolong survival in patients with androgen-independent prostate cancer”. According to Dahut, there has been a reluctance to use cytotoxic chemotherapy in patients with prostate cancer: “I am hopeful that these findings will lead to rapid [patient] accrual in trials testing chemotherapy [against] early stage disease”, comments Dahut. Howard Scher (Memorial SloanKettering Cancer Center, NY, USA) welcomes the findings, which “provide a foundation on which to build; and the justification to evaluate [the use of] docetaxel in earlier [stages of] disease— a paradigm that has resulted in great improvements in outcome for patients with lung, colon, breast, and other tumours where chemotherapy is [not very] effective”. Khabir Ahmad
PAI1: a useful biomarker for cervical cancer? Dutch researchers report that expression of plasminogen activator inhibitor 1 (PAI1) in tumour cells correlates with worse disease-free and overall survival in women with cervical cancer. “We need to reproduce our results in more patients”, says lead author Suzanne Hazelbag (Leiden University Medical Center, Netherlands), “but measurement of PAI1 expression might help clinicians decide how to treat patients after radical surgery for cervical cancer”. Cervical cancer is the second commonest cause of death from cancer in women worldwide. When prognostic markers such as tumour size are unfavourable, treatment of advanced disease generally involves radical surgery followed by radiotherapy. Unfortunately, says Hazelbag, “some patients, despite favourable prognostic markers at the time of surgery, return to us 6 months later with widespread disease”. In their search for further prognostic markers, Hazelbag and colleagues measured tumour express-
706
ion of transforming growth factor 1 (TGF1) and PAI1 in 108 patients for whom details of existing prognostic factors and outcome were available. Because cervical cancer is usually caused by human papillomavirus, explains Hazelbag, one step in cervical carcinogenesis is tumour escape from
Rights were not granted to include this image in electronic media. Please refer to the printed journal. Drawing up a biomarker for cervical cancer.
the host’s antiviral immune response. TGF1 is a multifunctional cytokine that causes immunosuppression. Hazelbag’s team has shown previously that TGF1 is produced by cervical cancer cells: “We included PAI1 in our study because its expression is induced by TGF1”, notes Hazelbag.
To the researchers’ surprise, there was no correlation between survival and TGF1 expression, but PAI1 expression in tumours was found to be a strong independent prognostic marker (Int J Cancer 2004; 112: 1020–28). “PAI1 expression has been correlated with worse survival in breast cancer, and two other groups have found some association with poor prognosis in cervical cancer. However, why expression of PAI1 should correlate with poor survival is unclear”, comments Hazelbag. “This interesting paper addresses the need to develop potential biomarkers for identifying advanced disease in cervical cancer”, note Subbi Mathur and William Creasman (Medical University of South Carolina, SC, USA). But, they add, a biomarker that could be measured non-invasively would be preferable. Hazelbag agrees and is now investigating whether blood concentrations of PAI1 correlate with treatment outcome in patients with cervical cancer. Jane Bradbury
Oncology Vol 5 December 2004
http://oncology.thelancet.com
3-month survival than did patients assigned mitoxantrone. There was also a reduction in pain and in concentrations of prostate-specific antigen. However, toxic effects were greater with docetaxel, and patients assigned it each week did no better than patients given standard treatment. In the second trial (N Engl J Med 2004; 351: 1513–20), Daniel Petrylak (Columbia University, Herbert Irving Comprehensive Cancer Center, NY, USA) and colleagues studied 770 patients with androgen-independent metastatic prostate cancer given docetaxel plus estramustine or mitoxantrone plus prednisone. Patients in the docetaxel group had better survival than those in other groups (17·5 months vs 15·6 months). This benefit was also associated with reduced PSA concentrations and improved progression-free survival. “These are extremely important studies”, says William Dahut (National
Cancer Institute, MD, USA), “because this is the first time any treatment has been shown to prolong survival in patients with androgen-independent prostate cancer”. According to Dahut, there has been a reluctance to use cytotoxic chemotherapy in patients with prostate cancer: “I am hopeful that these findings will lead to rapid [patient] accrual in trials testing chemotherapy [against] early stage disease”, comments Dahut. Howard Scher (Memorial SloanKettering Cancer Center, NY, USA) welcomes the findings, which “provide a foundation on which to build; and the justification to evaluate [the use of] docetaxel in earlier [stages of] disease— a paradigm that has resulted in great improvements in outcome for patients with lung, colon, breast, and other tumours where chemotherapy is [not very] effective”. Khabir Ahmad
PAI1: a useful biomarker for cervical cancer? Dutch researchers report that expression of plasminogen activator inhibitor 1 (PAI1) in tumour cells correlates with worse disease-free and overall survival in women with cervical cancer. “We need to reproduce our results in more patients”, says lead author Suzanne Hazelbag (Leiden University Medical Center, Netherlands), “but measurement of PAI1 expression might help clinicians decide how to treat patients after radical surgery for cervical cancer”. Cervical cancer is the second commonest cause of death from cancer in women worldwide. When prognostic markers such as tumour size are unfavourable, treatment of advanced disease generally involves radical surgery followed by radiotherapy. Unfortunately, says Hazelbag, “some patients, despite favourable prognostic markers at the time of surgery, return to us 6 months later with widespread disease”. In their search for further prognostic markers, Hazelbag and colleagues measured tumour express-
706
ion of transforming growth factor 1 (TGF1) and PAI1 in 108 patients for whom details of existing prognostic factors and outcome were available. Because cervical cancer is usually caused by human papillomavirus, explains Hazelbag, one step in cervical carcinogenesis is tumour escape from
Rights were not granted to include this image in electronic media. Please refer to the printed journal. Drawing up a biomarker for cervical cancer.
the host’s antiviral immune response. TGF1 is a multifunctional cytokine that causes immunosuppression. Hazelbag’s team has shown previously that TGF1 is produced by cervical cancer cells: “We included PAI1 in our study because its expression is induced by TGF1”, notes Hazelbag.
To the researchers’ surprise, there was no correlation between survival and TGF1 expression, but PAI1 expression in tumours was found to be a strong independent prognostic marker (Int J Cancer 2004; 112: 1020–28). “PAI1 expression has been correlated with worse survival in breast cancer, and two other groups have found some association with poor prognosis in cervical cancer. However, why expression of PAI1 should correlate with poor survival is unclear”, comments Hazelbag. “This interesting paper addresses the need to develop potential biomarkers for identifying advanced disease in cervical cancer”, note Subbi Mathur and William Creasman (Medical University of South Carolina, SC, USA). But, they add, a biomarker that could be measured non-invasively would be preferable. Hazelbag agrees and is now investigating whether blood concentrations of PAI1 correlate with treatment outcome in patients with cervical cancer. Jane Bradbury
Oncology Vol 5 December 2004
http://oncology.thelancet.com