Ovarian cancer advanced disease

As with many other disease states, a significant risk factor associated with ovarian cancer is aging. A womans risk increases from 15.7% to 54% per 100,000 as her age advances from 40 to 79 years, with the mean age at diagnosis being 59 years.2... 

Pelvic examinations are effective in detecting obvious tumors with a sensitivity of 67% for detecting all tumors minimal or microscopic disease cannot be detected on physical examination.9 Pelvic examinations are non-invasive and well accepted, but they do not usually detect ovarian cancer until it is in an advanced stage. Therefore, routine pelvic examinations will not improve earlier diagnosis or help to decrease overall mortality.9... 

Ovarian cancer often has been denoted as the "silent killer" because of the non-specific signs and symptoms. By the time symptoms become unrelenting and bothersome, patients have advanced stage disease. 

Other clinical uses for the gonadal suppression provided by continuous GnRH agonist treatment include advanced breast and ovarian cancer thinning of the endometrial lining in preparation for an endometrial ablation procedure in women with dysfunctional uterine bleeding and treatment of amenorrhea and infertility in women with polycystic ovary disease. 

TMCA) given orally daily for 5 days every 3 weeks were performed in 19 patients with advanced malignancies (139). Myelosuppression and mucositis were the major toxicities observed. Serum TMCA levels were monitored and appear to be useful in predicting toxicity. A partial response was seen in one lymphoma patient, and stabilization of disease was noted in two patients with prostatic or ovarian cancers. 

Compared to other solid tumors, ovarian cancer is relatively responsive to chemotherapy, but unlike testicular cancer, cure is not common for patients with advanced disease. Prior to the incorporation of cisplatin or carboplatin into treatment regimens, chemotherapy for advanced-stage ovarian cancer consisted of combinations of alkylating agents and doxorubicin. Response rates from such regimens were of the order of 33-65%, and fewer than 10% of patients survived 5 years [51]. 

Ovarian cancer patients with progressed disease often present with ascites/ peritoneal fluid. In some women, ovarian cysts are detected containing cystic fluid. The concentrations of suPAR in these body fluids were compared with those in serum made from peripheral blood and blood aspirated from the surface veins on the tumor in 77 patients admitted for surgery of ovarian tumors [21]. In this study, elevated levels of suPAR were measured in serum from peripheral blood and tumor blood in the patients with more advanced disease. However, the concentrations of suPAR in the body fluids were quite different, in serum the measured concentrations were between 46 and 98 pmol/liter, in ascites/peritoneal fluid concentrations were between 293 and 586 pmol/liter, and in cystic fluids the concentrations were even higher, that is 651-8468 pmol/liter. The concentrations of suPAR in cystic fluids clearly separated benign and malignant cysts with predictive values above 90%. The levels of suPAR in cystic fluids could therefore be used in the early diagnosis of ovarian cancer patients. The suPAR in the cystic fluids was present both in intact and cleaved forms and at least some of the suPAR(I-III) was not occupied by uPA [21]. In another study, tumor tissue, serum, ascites, and urine from ovarian cancer patients were analyzed for their content of the different uPAR forms. Whereas all of tumor lysates, ascites, and urine contained uPAR(I-III) and uPAR(II-III), domain I was only present in urine samples. In serum, only intact suPAR was detected [82], The antibodies used for identification were mAb R3 (domain I) and mAb R2 (domain III). 

The oncolytic viruses include adenovirus, measles, reovirus, vesicular stomatitis virus (VSV),HSV,poxvirus, and vaccinia. Specific examples include (1) ONYX-015, which is an adenoviral oncolytic virus, administered to patients with liver metastases of colorectal cancer and pancreatic cancer [29], (2) Reolysin, which is an oncolytic reovirus administered to patients with glioma [30], and (3) MV-CEA, which is an oncolytic measles virus expressing carcinoembryonic antigen, administered to patients with ovarian cancer [31]. Some oncolytic viruses are wild type and are apparently not pathogenic in humans, such as the Newcastle disease virus (NDV), which is an RNA avian paramyxovirus. PV701, a naturally attenuated, replication-competent strain of NDV, has been administered to patients with advanced solid tumors [32], The applicability of oncolytic viruses as a therapy for clinical oncology trials is due to their potential selectivity the ability to kill tumor cells but not normal cells. However, the level of attenuation of viral replication in normal cells is limited for most oncolytic vectors. 

Ovarian cancer is asymptomatic in its early stages and usually goes undetected until well advanced and difficult to treat. Screening for ovarian cancer has not yet been shown to be effective, partly for want of a preoperative technique to confirm or exclude malignancy in suspicious lesions that are identified by the screening process. In vivo MRS may offer such a method by early confirmation of ovarian cancers in high-risk women (i.e. with a family history of the disease) in whom screening would be warranted. 

Survival of patients with advanced ovarian cancer is a func- tion of stage at initial diagnosis and the amount of residual disease after surgical debulking. Patients with stage III dis-... 

The majority of women with ovarian cancer present with stage III or IV disease. The approach to the treatment of advanced ovarian cancer is initial surgical debuUdng followed by ad-juvant/consolidative paclitaxel plus cisplatin or carboplatin for six cycles (see Fig. 130-2). Overall survival is a function of the initial disease stage (stage III vs. IV) and the amount of residual disease left after surgical debuUdng. 

The NCCN guidelines recommend three to six cycles of treatment for lower stage tumors and at least six cycles of treatment for patients with stage III or IV disease. However, results of a recent randomized study showed that 12 months of maintenance pachtaxel significantly prolongs the duration of progression-free survival in patients with advanced ovarian cancer who attain a complete response to initial platinum and paclitaxel-based chemotherapy. ... 

The choice of retreatment with platinum-containing chemotherapy depends on the time frame in which the disease recurs. Patients with advanced ovarian cancer that experience disease recurrence following initial chemotherapy are divided into two therapeutic groups. Patients who do not respond to the initial platinum-containing chemotherapy or who have recurrence within 6 months after discon-... 

A phase III trial examined a total of 462 eligible patients with small (<1 cm in maximal diameter), residual, advanced ovarian cancer who were randomized to receive two comses of either carboplatin (AUC = 9) followed by IV pachtaxel 135 mg/m over 24 honrs and IP cisplatin 100 mg/m every 21 days for six cycles, or IV paclitaxel 135 mg/m over 24 hours and IV cisplatin 75 mg/m every 21 days for six cycles. Progression-free survival was superior in the IP arm versus the IV arm (median 27.9 months vs. 22.2 months, respectively). Overall survival was 63.2 months in the IP arm versus 52.2 months in the IV arm. Although a significant improvement in progression-free survival was observed, toxicity was much greater in the experimental arm. Results from this study provide future direction for clinical studies in patients with smaU-volume disease. ... 

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