Combination Platinum Based Chemotherapy versus Single Agent Platinum

If a patient is to receive a platinum agent, the next question is: Should the platinum drug be administered alone or in combination with a second non-platinum drug?

Figure 9-3. Up to 15% to 20% of women receiving a second-line platinum-based chemotherapy program will experience a toxic reaction. (Data from Markman M, Kennedy A, Webster K, et al: Clinical features of hypersensitivity reactions to carboplatin. J Clin Oncol 17:1141, 1999, Table 1.)

Table 9-3. Phase III Randomized Trials of Combination Platinum-Based Therapy versus Single-Agent Platinum in Recurrent Ovarian Cancer

Response Rate

Progression-Free Survival (Median)

Overall Survival (Median)

Carboplatin + paclitaxel versus carboplatin (ICON-4)10

66% vs 54% (P = .06)

12 vs 9 months (HR 0.76, P = .0004)

29 vs 24 months (HR 0.82, P = .02)

Carboplatin + gemcitabine versus carboplatin (AGO)11

47.2% vs 30.9% (P = .016)

8.6 vs 5.8 months (HR 0.72, P = .003)

18 vs 17.3 months (HR 0.96, P = .74)

Data from The ICON and AGO Collaborators. Paclitaxel plus platinum-based chemotherapy versus conventional platinum-based chemotherapy in women with relapsed ovarian cancer: the ICON4/AGO-OVAR-2.2 trial. Lancet 361:2099-2106, 2003; Pfisterer J, Plante M, Vergote I, et al: Gemcitabine plus carboplatin compared with carboplatin in patients with platinum-sensitive recurrent ovarian cancer: an intergroup trial of the AGO-OVAR, the NCIC CTG, and the EORTC GCG. J Clin Oncol 24:4699-4707, 2006.

Data from The ICON and AGO Collaborators. Paclitaxel plus platinum-based chemotherapy versus conventional platinum-based chemotherapy in women with relapsed ovarian cancer: the ICON4/AGO-OVAR-2.2 trial. Lancet 361:2099-2106, 2003; Pfisterer J, Plante M, Vergote I, et al: Gemcitabine plus carboplatin compared with carboplatin in patients with platinum-sensitive recurrent ovarian cancer: an intergroup trial of the AGO-OVAR, the NCIC CTG, and the EORTC GCG. J Clin Oncol 24:4699-4707, 2006.

The results of two phase III randomized trials have provided important support for the conclusion that combination platinum-based chemotherapy is therapeutically superior to single-agent platinum when used in recurrent ovarian cancer10,11 (Table 9-3).

The first reported trial (International Collaborative Ovarian Neoplasm [ICON]-4) was rather complex in its design, but it is reasonable to conclude that the study essentially compared a regimen of single-agent carboplatin with the combination of carboplatin plus paclitaxel.10 This trial revealed an improvement in both progressionfree and overall survival in favor of the combination program. At 2 years' follow-up, a 7% absolute improvement (57% versus 50%) was seen in overall survival in favor of the carboplatin plus paclitaxel regimen.

Unfortunately, this clear survival benefit must be viewed in the context of the documented substantial increase in neurotoxicity observed in the population randomized to the combination regimen, compared with single-agent carboplatin (grades 2-3: 20% versus 1%)10 (Fig. 9-4).

The second reported randomized study in recurrent ovarian cancer directly compared single-agent carboplatin with the combination of carboplatin plus gemcitabine.11 This trial also demonstrated an improvement in progression-free survival associated with the combination program, but surprisingly (in view of the previously known results from ICON-4), no improvement in overall survival.

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