Familial Nasopharyngeal Carcinoma 6

154 B. B. Y. Ma and A. T. C. ChanTable 11.1 Selected cytotoxic chemotherapy with known activity against nasopharyngeal carcinoma in the palliative or neoadjuvantsettingDrug Single agent: RR (%) Combination with other drugs: RRPlatinumCisplatin NA a5-FU: 66% (Au and Ang 1994)bDocetaxel: 76% (Hui et al. 2009)aGemcitabine: 73% (Ngan et al. 2002)Carboplatin a44% (Chi et al. 1997) a5-FU: 38% (Yeo et al. 1996)aPaclitaxel: 59% (Yeo et al. 1998)Oxaliplatin NA aGemcitabine: 56% (Ma et al. 2009)Non-platinumBleomycin a28% (Molinari 1978)aCisplatin, 5-FU: 79% (Boussen et al. 1991)aCisplatin, epirubicin: 48% (Azli et al. 1995)bCisplatin, epirubicin: 98% (Bachouchi et al. 1990)Capecitabine a37% (Chua et al. 2008) aCisplatin: 62% (Li et al. 2008)Cyclophosphamide a38% (Molinari 1978) aCAPABLE: 80% (Siu et al. 1998)Docetaxel NA aCisplatin: 22% (Mccarthy et al. 2002)bCisplatin: 76% (Hui et al. 2009)Doxorubicin 39% (Molinari 1978) aCAPABLE: 80% (Siu et al. 1998)5-FU (infusional) 25% (Fandi et al. 1997) See under “cisplatin” and “carboplatin”Gemcitabine a28% (Foo et al. 2002) aCisplatin: 73% (Ngan et al. 2002)aCarboplatin, paclitaxel: 78% (Leong et al. 2005)Ifosfamide NA aCisplatin: 59% (Stein et al. 1996)Irinotecan c14% (Poon et al. 2005) NAMethotrexate 17% (Molinari 1978) See under “CAPABLE”Paclitaxel 22% (Au et al. 1998) See under “carboplatin”Vinorelbine NA cGemcitabine: 36% (Wang et al. 2006)NA not available; RR response rate (partial and complete response); 5-FU 5-fluorouracil; CAPABLE 5-drug regimen with cyclophosphamide,doxorubicin, cisplatin, methotrexate, and bleomycinaPalliative first-line studybNeoadjuvantcPalliative second- or third-line study11.3.3.3Molecular Factors Affecting Cellular Response toChemotherapy in Nasopharyngeal CarcinomaAltered expression of cell cycle regulators and EBVrelatedproteins has been implicated as factors affectingcellular response to cisplatin in preclinical studiesof NPC. For instance, NPC cells transfected with theoncogenic EBV-encoded latent membrane protein-1(LMP-1) were up to four times more susceptible tocisplatin-induced cell death than LMP-1 negativeNPC cells (Liu et al. 2002).The cytotoxicity of cisplatin is cell cycle- dependent,such that rapidly proliferating cells are more susceptibleto its action. Researchers have evaluated the associationbetween some cell cycle checkpoint regulatorsand sensitivity to DNA-damaging agents in NPC cells.The mitotic arrest deficient 2 protein (MAD2) regulatesthe mitotic checkpoint, which ensures the accuratesegregation of chromosomes (Wang and Wong 2003).