Cisplatin versus carboplatin

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International Collaborative Ovarian Neoplasm Group. Paclitaxel plus carboplatin versus standard chemotherapy with either single-agent carboplatin or cyclophosphamide, doxorubicin and cisplatin in women with ovarian cancer the ICON3 randomized trial. Lancet 2002 360 505-515. 

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The most frequently used regimen is cisplatin or carboplatin combined with etoposide. Irinotecan in combination with cisplatin has also been shown to be active (see Table 63-1). Overall response rates and survival durations are generally superior for patients with limited stage versus those with extensive stage disease. 

Vail DM, Kurzman ID, Glawe PC, O Brien MG, Chun R, Garrett LD, Obradovich JE, Fred RM 3rd, Khanna C, Colbern GT, Working PK. STEALTH liposome-encapsulated cisplatin (SPI-77) versus carboplatin as adjuvant therapy for spontaneously arising osteosarcoma (OSA) in the dog a randomized multicenter clinical trial. Cancer Chemother Pharmacol 2002 50(2) 131-6. 

Cisplatin (C) + paclitaxel (P) or gemcitabine (G) or docetaxel (D) versus carboplatin (Cb) 4- paclitaxel... 

Carboplatin is often substituted for cisplatin in numerous SCLC regimens and has been shown to have similar efficacy with somewhat less toxicity, particularly for patients with pre-existing renal dysfunction or severe neuropathy. In a randomized comparison of carboplatin and etoposide (CE) versus PE in patients with SCLC, the overall survival was 11.8 months for the CE group and 12.5 months for the PE group. Based on these data, PE or CE have become the most commonly used regimens to treat SCLC in the United States. 

A phase III trial examined a total of 462 eligible patients with small (<1 cm in maximal diameter), residual, advanced ovarian cancer who were randomized to receive two comses of either carboplatin (AUC = 9) followed by IV pachtaxel 135 mg/m over 24 honrs and IP cisplatin 100 mg/m every 21 days for six cycles, or IV paclitaxel 135 mg/m over 24 hours and IV cisplatin 75 mg/m every 21 days for six cycles. Progression-free survival was superior in the IP arm versus the IV arm (median 27.9 months vs. 22.2 months, respectively). Overall survival was 63.2 months in the IP arm versus 52.2 months in the IV arm. Although a significant improvement in progression-free survival was observed, toxicity was much greater in the experimental arm. Results from this study provide future direction for clinical studies in patients with smaU-volume disease. ... 

Taylor AE, Wiltshaw E, Gore ME, et al. Long-term followup of the first randomized study of cisplatin versus carboplatin for advanced epithelial ovarian cancer. J Clin Oncol 1994 12 2066-2070. 

Swenerton K, Jeffrey J, Stuart G, et al. Cisplatin-cyclophosphamide versus carboplatin-cyclophosphamide in advanced ovarian cancer A randomized phase III study of the National Cancer Institute of Canada Clinical Trials Group. J Clin Oncol 1992 10 718-726. 

Neijt JP, Engelholm SA, Tuxen MK, et al. Exploratory phase III study of paclitaxel and cisplatin versus paclitaxel and carboplatin in advanced ovarian cancer. J Clin Oncol 2000 18 3084-3092. 

Numerous clinical trials have demonstrated that carboplatin is substantially less toxic (especially in terms of nephrotoxicity and gastrointestinal effects see Table 1) than is cisplatin. Overview analyses of randomised studies comparing the activity of cisplatin versus that of carboplatin (mainly in ovarian and testicular cancers) have concluded that the two are broadly comparable in terms of response rates and disease-free intervals. However, it also appears that the two drugs are effective against the same population of tumours and thus share cross-resistance with one another. Notably, however, secondary responses to... 

While some have advocated replacing cisplatin with the less toxic carboplatin as first-line treatment for all patients with ovarian tumours, this issue remains contentious, both with respect to cost and because many of the randomised studies of cisplatin versus carboplatin are still, in the context of clinical trials, in relatively early stages without long-term follow up. 

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