Definition of Recurrent versus Platinum Resistant Ovarian Cancer

It has long been recognized that ovarian cancer patients whose tumors exhibit objective evidence of a response to chemotherapy may respond a second time to the same (or a similar) treatment program.3,4 In fact, this observation is not unique to ovarian cancer, having been demonstrated relatively early in the development of modern chemotherapy in the management of hematologic malignancies.5

Because of the central role of the platinum agents in ovarian cancer,6 it should come as no surprise that the greatest experience with re-treatment in this malignancy has been with platinum-based strategies, delivered either as single agents or as a component of a combination chemotherapy program.7-11 As a result of its more favorable toxicity profile, carboplatin is generally the platinum of choice in the second-line setting.2

It has also been demonstrated that the opportunity that a particular individual's ovarian cancer will respond a second (or third, etc.) time to a platinum-based chemotherapy is a continuum, with the longer the duration of the platinum- or treatment-free interval, the greater the statistical likelihood that the patient will again experience objective and subjective benefit from this approach7-9 (Table 9-1; Fig. 9-1).

Thus, for a woman who develops recurrent disease approximately 8 to 10 months after completing primary treatment, the probability of a second response ranges from 20% to 30%. However, for the patient experiencing disease recurrence with a treatment-free interval of 2 years, the chances of her experiencing a response to re-treatment is greater than 50%.

For the purpose of designing relatively homogeneous prospective clinical trials, "platinum-resistant" and "recurrent" (potentially platinum-sensitive) disease has been defined12,13 (Box 9-1). Again, it is critical to remember that although these defi-

Table 9-1. Relationship Between Response Rates to Second-Line Platinum-Based Chemotherapy and the Platinum or Treatment-Free Interval

Platinum-Free Interval Percentage

G-6 months 1G

7-12 months 2G-3G

13-18 months 3G-4G

19-24 months 4G-5G

>24 months >5G

Data from references 7, S, and 9.

Time since start of second treatment (years)

Figure 9-1. Survival from the start of treatment for relapse (second treatment). The time lapsed since the end of treatment to relapse has a tremendous bearing on probability of survival. Lighter red, relapse or progression within 18 months of completing initial treatment; darker red, relapse or progression after 18 months of completing initial treatment. (From Gore ME, Fryatt I, Wiltshaw E, et al: Treatment of relapsed carcinoma of the ovary with cisplatin or carboplatin following initial treatment with these compounds. Gynecol Oncol 36:207-211, 1990, Fig. 3.)

Box 9-1. Definition of Recurrent and Platinum-Resistant Ovarian Cancer

Recurrent ovarian cancer:

Prior response to a platinum-based chemotherapy regimen and a treatment-free interval of >6 months

Platinum-resistant ovarian cancer:

No response to prior platinum-based chemotherapy (e.g., "best response" stable disease or actual disease progression) or response to platinum-based therapy with a treatment-free interval of <6 months

Box 9-2. Considerations in the Selection of Second-Line Therapy in Ovarian Cancer

• Prior response to treatment (Including treatment-free Interval)

• Toxicity from prior therapy (Including any residual effects)

• Evidence-based phase III trial data supporting strategies in the particular setting (e.g., recurrent disease)

• Non-evidence-based (phase II studies) supporting potential treatment programs

• Availability of, and interest in, clinical trials

• Patient choice

Box 9-3. Reasonable Objectives of Second-Line Therapy of Ovarian Cancer

1. Extend survival

2. Improve cancer-related symptoms

3. Prolong the time to the development or worsening of symptoms

4. Prolong the time to the documentation of progressive disease

5. Improve or maintain overall quality of life nitions are useful (particularly in the context of eligibility criteria for clinical studies), no single duration of a platinum- or treatment-free interval can specifically differentiate the individual patient who will, or will not, achieve benefit from re-treatment with a platinum drug. Selection of optimal therapy in this setting must include consideration of available trial data (especially evidence-based randomized phase III studies), the toxicity previously experienced by the patient during prior treatment regimens, and patient choice (Box 9-2).

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