Chemotherapy of Recurrent Potentially Platinum Sensitive Ovarian Cancer

As previously noted, there is very strong evidence to support delivery of a platinum-based chemotherapy regimen in the second-line setting in women who have previously experienced an objective response to therapy with this class of drugs.7-11 Unfortunately, there has been a rather profound absence of evidence-based studies that have directly compared a platinum-based regimen with a non-platinum program in the setting of recurrent ovarian cancer. However, the limited randomized experience does suggest superiority of a platinum-containing program in this clinical setting14 (Table 9-2; Fig. 9-2).Despite this fact, there are a number of reasons why an individual physician and patient may decide to avoid platinum in the second-line setting, despite a prior response to the drug (Box 9-4).

The risk for the development of a platinum-associated hypersensitivity reaction is increasingly recognized as an important concern in this patient population. Up to 15% to 20% of women receiving a second-line platinum-based chemotherapy program experience this toxic reaction, with signs and symptoms ranging from a mild rash to cardiovascular and respiratory arrest15,16 (Fig. 9-3). Fatal episodes related to re-treatment with a platinum agent following the demonstration of a platinum allergy have been reported.17

Several desensitization programs have been developed to permit the continuation of therapy with platinum in this patient population, with a variable degree of reported success.18-20 These programs are patterned after strategies used in individuals documented to have hypersensitivity to antibiotics (e.g., penicillin), in which initiation or continuation of treatment with the agents is highly relevant, despite the potential risk.

The decision to continue a patient with a platinum drug in this setting should reasonably be based on several factors, including: (a) severity of the reaction; (b) objective evidence for the activity of the second-line program that contains the platinum (e.g., major reduction in abdominal pain or disappearance of symptomatic

Table 9-2. Combination Platinum-Based Chemotherapy versus a Non-Platinum Regimen in Recurrent Ovarian Cancer

Progression-free Survival Complete Response (Median) Overall Survival (Median)

Paclitaxel 17% 9 months 25.8 months

CAP 30% 15.7 months (P = .038) 34.7 months (P = .043)

CAP, cyclophosphamide, doxorubicin, clsplatln.

Data from Cantu MG, Buda A, Parma G, et al: Randomized controlled trial of single-agent paclitaxel versus cyclophosphamide, doxorubicin, and cisplatin in patients with recurrent ovarian cancer who responded to first-line platinum-based regimens. J Clin Oncol 20:1232-1237, 2002.

Box 9-4. Reasons for Not Using Platinum-Based Therapy in Recurrent Ovarian Cancer

• Prior serious acute toxicity (e.g., severe emesis; grade 3 neuropathy; grade 3-4 thrombocytopenia)

• Persistent toxicity, even if not severe (e.g., grade 1 neuropathy)

• Highly unpleasant adverse effects of prior platinum therapy (e.g., grade 1-2 emesis lasting 5-7 days after each treatment)

• Development of a clinically relevant platinum hypersensitivity reaction

• Modest activity of prior platinum therapy (e.g., treatment-free interval of only 6-8 months)

Years from randomization

Events

Totals

CAP

37

47

Paclitaxel

41

47

Years from randomization

Events

Totals

CAP

27

47

Paclitaxel

34

47

Figure 9-2. Comparison of single-agent versus multiagent therapy. A, Kaplan-Meier plot of progression-free intervals by treatment. B, Kaplan-Meier plot of overall survival by treatment. Few evidence-based studies directly compare a platinum-based regimen with a non-platinum program in the setting of recurrent ovarian cancer. However, the limited randomized experience does suggest superiority of a platinum-containing program. CAP, cyclophosphamide, doxorubicin (Adriamycin), and cisplatin. (Data from Cantu MG, Buda A, Parma G, et al: Randomized controlled trial of single-agent paclitaxel versus cyclophosphamide, doxorubicin, and cisplatin in patients with recurrent ovarian cancer who responded to first-line platinum-based regimens. J Clin Oncol 20:1232-1237, 2002, Figs. 2 and 3.)

ascites versus a minimal fall in the CA-125 level after the initial course of second-line platinum); (c) available alternative options; and (d) patient choice.21 Patients and their families need to be included in the discussion regarding re-treatment with a platinum agent after the development of platinum hypersensitivity, since the risk of a severe, even fatal, reaction is more than a theoretical possibility.17

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