Ovarian Epithelial Cancer Treatment - Recurrent or Persistent Ovarian Epithelial Cancer Treatment
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Overall, approximately 80% of patients diagnosed with ovarian epithelial cancer will relapse after first-line platinum-based and taxane-based chemotherapy and may benefit from subsequent therapies; however, subsequent evidence questions this practice. Early detection of persistent disease by second-look laparotomies after completing first-line treatment is no longer practiced; when the outcomes in the 50% of institutions practicing such procedures were informally compared with the outcomes in those institutions not using such procedures, additional lack of support for them grew, as was found in the case for patients entered in GOG-0158. However, the practice of close follow-up of patients completing treatment by serial CA 125s at intervals of 1 to 3 months was nearly universally adopted. In patients who are in clinical complete remission, increases in CA 125 from their initial treatment represent the most common method to detect disease that will eventually relapse clinically.
A trial by the Medical Research Council and European Organization for Research and Treatment of Cancer (MRC-OV05) examined the consequences of early institution of treatment for recurrence versus treatment delayed until clinical symptoms appeared. Patients in clinical complete remission after platinum-based chemotherapy were registered and followed with CA 125s only and clinical visits. Upon detection of a twofold elevation over the normal range, patients were randomly assigned to disclosure of the result (and early treatment for recurrence) versus continued blinding and treatment upon development of signs and symptoms indicative of clinical relapse. The number of randomly assigned patients was to exceed 500 in order to yield a superior survival outcome at 2 years with early institution of therapy; this required 1,400 registrations, which were accrued between May 1996 and August 2005. Among 1,442 registrants, 29% continued to show no evidence of relapse, 19% relapsed without evidence of CA 125 doubling beyond normal or at the same time, and another 4% died prior to becoming eligible for random assignment. Registrants had stage III and stage IV disease in 67% of the cases, whereas these stages represented 80% of the randomly assigned patients. The median survival of all patients registered was 70.8 months.
Median survival for patients randomly assigned to early treatment (n = 265) was 25.7 months compared with 27.1 months for those patients in the delayed-treatment group (n = 264) (HR = 0.98, 95% CI, 0.8-1.2). The median delay in instituting second-line chemotherapy was 4.8 months, and the median delay in instituting third-line chemotherapy was 4.6 months. Treatments for second-line chemotherapy were comparable among the two groups (mostly platinum- and taxane-based), whereas third-line treatments were less often applied to the delayed-treatment group. The study concluded that there was no benefit in the detection of early presence of disease by CA 125; this is consistent with the failure of second-look surgeries to provide improved outcomes after early detection of persistent disease. Monitoring CA 125 levels in follow-up may play a role in identifying appropriate candidates for secondary cytoreduction, although this strategy awaits confirmation with a randomized trial.