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Discussion: session 2 Josep M del Campo*1, Jalid Sehouli2 & Domenica Lorusso3 Gynecological, Head & Neck Cancer Division, Department of Medical Oncology, Vall d’Hebron University Hospital, Barcelona, Spain 2 Department of Gynecology, European Competence Center for Ovarian Cancer, Campus Virchow Klinikum, Charité University Hospital, Berlin, Germany 3 Gynecologic Oncology Unit, Fondazione `IRCCS’ National Cancer Institute, Milan, Italy *Author for correspondence: Tel: +34 93 4894350 n Fax:+34 93 2746781 n [email protected]
What do you usually do in your hospital when a patient develops hypersensitivity to platinum? Josep M del Campo
Drugs can cause allergic reactions via a range of immunologic mechanisms which, as yet, are either unknown or poorly understood. These drug reactions may be mediated immunologically: mast cells and basophils are the critical components mediated by IgE, and mast cells release mediators (e.g., histamine, arachidonic acid metabolites [leukotrienes and prostaglandins], proteases and proteoglycans) that lead to classic cutaneous, respiratory, cardiovascular and gastrointestinal symptoms. In ovarian cancer patients, carboplatin is responsible for up to approximately 27% of hypersensitivity reactions (HSRs), with approximately 50% of initial HSRs occurring during the eighth course of treatment, usually starting within 30 min of infusion and despite premedication with dexamethasone and antihistamines. Other antineoplastic drugs lead to HSRs with varying rates (paclitaxel/docetaxel: 10–30%; cabazitaxel: 0.3–1.8%; cetuximab: 16–19%; trastuzumab: 40%; rituximab: 77%) [1–4]. The retreatment interval has also been shown to be important with regard to carboplatin-related HSRs. A retreatment interval >23 months has been associated with a 36% incidence of HSRs, compared with a HSR incidence of 8% with a retreatment interval 12 months, trabectedin/PLD has been shown to result in an OS of 36.5 months , in the range observed with platinum combinations, and it is associated with a different safety profile to platinum combinations. In particular, trabectedin/ PLD is not associated with cumulative end-organ toxicities (renal, cardiac or neurological) or adverse effects such as alopecia, HSRs, hand–foot syndrome or mucositis . As such, for patients with fullysensitive recurrent ovarian cancer (platinum-free interval: >12 months), combination of trabectedin/ PLD may represent an alternative treatment option. ovarian cancer in late relapse. J. Clin. Oncol. 28, 3323–3329 (2010).
Parmar MK, Ledermann JA, Colombo N et al. Paclitaxel plus platinum-based chemotherapy versus conventional platinum-based chemotherapy in women with relapsed ovarian cancer: the ICON4/AGOOVAR-2.2 trial. Lancet 361, 2099–2106 (2003).
Pujade-Lauraine E, Wagner U, Aavall-Lundqvist E et al. Pegylated liposomal doxorubicin and carboplatin compared with paclitaxel and carboplatin for patients with platinum-sensitive
Future Oncol. (2013) 9(12 Suppl. 1)
Gladieff L, Ferrero A, De Rauglaudre G et al. Carboplatin and pegylated liposomal doxorubicin versus carboplatin and paclitaxel in partially platinum-sensitive ovarian cancer patients: results from a subset analysis of the CALYPSO Phase III trial. Ann. Oncol. 23, 1185–1189 (2012).
Wagner U, Marth C, Largillier R et al. Final overall survival results of Phase III GCIG CALYPSO trial of pegylated liposomal doxorubicin and carboplatin
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Discussion: session 2
vs paclitaxel and carboplatin in platinum-sensitive ovarian cancer patients. Br. J. Cancer 107, 588–591 (2012). 5.
Aghajanian C, Blank SV, Goff BA et al. OCEANS: a randomized, double-blind, placebo-controlled Phase III trial of chemotherapy with or without bevacizumab in patients with platinum-sensitive recurrent epithelial ovarian, primary peritoneal, or fallopian tube cancer. J. Clin. Oncol. 30, 2039–2045 (2012). Aghajanian C, Nycum LR, Goff B, Nguyen H, Husain A, Blank SV. Updated overall survival ana lysis in OCEANS, a randomized Phase 3 trial of gemcitabine + carboplatin and bevacizumab or placebo followed by bevacizumab or placebo in platinum-sensitive recurrent epithelial ovarian, primary peritoneal, or fallopian tube cancer. Presented at: the European Society for Medical Oncology. Vienna, Austria, 28 September–2 October 2012.
Monk BJ, Herzog TJ, Kaye SB et al. Trabectedin plus pegylated liposomal doxorubicin in recurrent ovarian cancer. J. Clin. Oncol. 28, 3107–3114 (2010).
Monk BJ, Herzog TJ, Kaye SB, et al. Final survival results of the randomized Phase III study of trabectedin with pegylated liposomal doxorubicin (PLD) versus PLD in recurrent
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ovarian cancer. J. Clin. Oncol. 29(Suppl.), Abstract 5046 (2011). 9.
Dunton CJ. Management of treatment-related toxicity in advanced ovarian cancer. Oncologist 7(Suppl. 5), 11–19 (2002).
10. 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). 11. González Martín A. Safety profile of trabectedin
in combination with liposomal pegylated doxorubicin in relapsed ovarian carcinoma: considerations for optimal management. Int. J. Gynecol. Cancer 21(Suppl. 1), S6–S8 (2011). Financial & competing interests disclosure
The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties. Editorial assistance was provided by Content Ed Net, with funding from PharmaMar, Madrid, Spain.