1.0 General Statements
1.1 Each patient is unique in her disease. Patients must be considered as a whole when making treatment recommendations. The basic principle is to use the most effective regimen or single agent. If the alternatives are equally effective, then choose treatment based upon toxicity, convenience, and availability.
1.2 Whenever clinical trials are available, all patients should be offered participation in these trials.
1.2a Systemic therapy for recurrent ovarian cancer is not curative.
1.2b The goals of treatment should be to improve quality of life (or symptom free interval or symptom intensity), or increase the progression free interval.
1.3 Women can be subdivided into three groups predictive of response to further platinum analogues: platinum-refractory (their cancer progresses upon treatment) who will not respond to platins; platinum-resistant (cancer recurs objectively within 6 months of completing treatment)—they have a 10% response rate to further platins; and platinum-sensitive (recurs more than 6 months after completing treatment)—they have a 30% predicted response rates with platinum retreatment. These latter two definitions are arbitrary and merely reflect an artificial cutpoint chosen to best delineate higher and lower response rates to subsequent treatment.
1.4 Repeated courses of chemotherapy can be effective in selected patients. As a principle, re-utilize the previous effective drug(s) until progression, (see section 1.1 above for principles) or undue toxicity adversely impacting quality of life or treat for a defined number of cycles.
2.0 Platinum Sensitive Disease
2.1 Whenever clinical trials are available, all patients should be offered participation in these trials.
2.2 Patients who experience a long treatment free interval of at least one year after exposure to platinum based chemotherapy should have the opportunity for retreatment with either platinum based combination or monotherapy. Platinum based combination therapy should be considered in these patients.
2.3 Single agent platinum therapy is preferable for those patients who have experienced significant toxicities (unless the platin was the responsible agent).
2.4 If a platinum compound is not warranted due to toxicity, then choice of systemic agent should be based on their toxicity profile, ease of administration, and availability.
3.0 Platinum Resistant Disease
3.1 Whenever clinical trials are available, all patients should be offered participation in these trials.
3.2 In a setting where clinical trials are not available or not appropriate, there are many treatment options which have shown modest response rate but their benefit over best supportive care has not been studied in clinical trials.
3.3 Drugs with proven efficacy in this setting include etoposide (Naumann et al., 1997; Rose et al., 1998; Kuhn et al., 1996), gemcitabine (Shapiro et al., 1996; Kaufmann & von Minckwitz, 1997; Coenen et al., 2000; von Minckwitz et al., 1999), liposomal doxorubicin (Muggia et al., 1997; Medi-View Express Report, 1999; Gordon et al., 2000), taxanes (Markman et al., 2000; Markman et al., 2002), topotecan (Creemers et al., 1996; Bookman et al., 1998; Hochster et al., 1999; Malmstrom, Sorbe, & Simonsen, 1996; Swisher et al., 1997; Markman et al., 1999), or vinorelbine (Burger et al., 1999; Bajetta et al., 1996).
See Tables 1, 2, and 3 and list of chemotherapeutic agents in the original guideline document, which have been assessed in randomized controlled trials (RCTs) in patients who are platinum resistant. The end points of effectiveness (response rate [RR], Survival, and toxicity are outlined.
4.0 Platinum Refractory Disease
4.1 Whenever clinical trials are available, all patients should be offered participation in these trials.
4.2 Patients who progress while upon a platin analogue should be switched to another drug (or to symptom management alone) following principles articulated in section 1.1 above.
5.0 Stopping Chemotherapy
As a patient is treated with repeated regimens of chemotherapy, there may be diminishing benefits in terms of duration and degree of response. There is a single institution Canadian study (Hoskins & Le, 2005) which has shown that survival is less than 6 months when the length of interval between the two preceding relapses is less than 12 months from the 1 to 2nd relapse and less than 6 months from the 1st to 3rd, or 2nd to 4th and so on. Thus, patients and their support network need to be apprised of the situation and the purpose of further interventions. Best supportive care based on the patient's current presentation (i.e., pain then appropriate pain relief) should always be an option.
