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Nasopharyngeal cancer (NPC) is a highly prevalent and invasive head and neck cancer in Asia. Disease recurrence and distant metastasis account for major NPC deaths. Therefore, more effective therapy is needed. Lapatinib, a dual tyrosine kinase inhibitor (TKI) against both EGFR and HER-2, has been known to exert potent antitumor activity against several cancer models. Given that both EGFR and HER-2 are co-expressed in NPC, we hypothesized that dual targeting of EGFR and HER-2 by this small molecule EGFR/HER-2 TKI would elicit anti-tumor activity in NPC. Using in vitro models of NPC, we demonstrated that lapatinib was able to efficiently inhibit the phosphorylation of both EGFR and HER-2. This was accompanied by significant growth inhibition of NPC cells (with maximal growth inhibition >90%). For the most lapatinib-sensitive cell line (HK1-LMP1, with IC(50) ∼ 600 nM), which harbored the highest levels of both EGFR and HER-2, inhibition of cell growth was associated G(0)/G(1) cell cycle arrest, marked PARP cleavage, caspase-3 cleavage, as well as significant downregulation of several important survival proteins (e.g. survivin, Mcl-1 and cyclin D1). NPC cells are intrinsically invasive. We found that lapatinib was able to inhibit cellular invasion of both HK1-LMP1 and HONE-1 cells. Furthermore, our data demonstrated for the first time that lapatinib harbored potent anoikis-sensitization activity (i.e. sensitizing cancer cells to detachment-induced apoptosis) in human cancer cells overexpressing both EGFR and HER-2 (HK1-LMP1 and HK1). Taken together, our findings suggest that lapatinib is a promising anti-cancer agent for NPC with anti-invasion and anoikis-sensitization activities.

Purpose: We aimed to validate the Multinational Association for Supportive Care in Cancer (MASCC) risk index, and compare it with the Talcott model and artificial neural network (ANN) in predicting the outcome of febrile neutropenia in a Chinese population., Methods: We prospectively enrolled adult cancer patients who developed febrile neutropenia after chemotherapy and risk classified them according to MASCC score and Talcott model. ANN models were constructed and temporally validated in prospectively collected cohorts., Results: From October 2005 to February 2008, 227 consecutive patients were enrolled. Serious medical complications occurred in 22% of patients and 4% died. The positive predictive value of low risk prediction was 86% (95% CI = 81-90%) for MASCC score ≥ 21, 84% (79-89%) for Talcott model, and 85% (78-93%) for the best ANN model. The sensitivity, specificity, negative predictive value, and misclassification rate were 81%, 60%, 52%, and 24%, respectively, for MASCC score ≥ 21; and 50%, 72%, 33%, and 44%, respectively, for Talcott model; and 84%, 60%, 58%, and 22%, respectively, for ANN model. The area under the receiver-operating characteristic curve was 0.808 (95% CI = 0.717-0.899) for MASCC, 0.573 (0.455-0.691) for Talcott, and 0.737 (0.633-0.841) for ANN model. In the low risk group identified by MASCC score ≥ 21 (70% of all patients), 12.5% developed complications and 1.9% died, compared with 43.3%, and 9.0%, respectively, in the high risk group (p < 0.0001)., Conclusions: The MASCC risk index is prospectively validated in a Chinese population. It demonstrates a better overall performance than the Talcott model and is equivalent to ANN model.

Purpose: Reactivation of hepatitis B virus (HBV) infection is a well-recognized complication in cancer patients with chronic HBV (hepatitis B surface antigen [HBsAg] positive) undergoing cytotoxic chemotherapy. In patients who have resolved HBV (HBsAg negative and antibody to hepatitis B core antigen [anti-HBc] +/- antibody to hepatitis B surface antigen [anti-HBs] positive), such incidence has been much less common until recent use of rituximab. In this study on HBsAg-negative/anti-HBc-positive lymphoma patients, the objectives were to determine the HBV reactivation rate in patients treated with rituximab-containing chemotherapy and to compare it with the rate in patients treated without rituximab., Patients and Methods: Between January 2003 and December 2006, all patients diagnosed with CD20(+) diffuse large B-cell lymphoma (DLBCL) had HBsAg determined before anticancer therapy. They were treated with either cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) alone or rituximab plus CHOP (R-CHOP). HBsAg-negative patients had anti-HBc determined; serum was stored for anti-HBs and HBV DNA. All patients were observed for HBV reactivation, which was defined as detectable HBV DNA with ALT elevation during and for 6 months after anticancer therapy., Results: Among 104 CD20(+) DLBCL patients, 80 were HBsAg negative. Of the latter, 46 patients (44.2%) were HBsAg negative/anti-HBc positive; 25 of these patients were treated with CHOP, and none had HBV reactivation. In contrast, among the 21 patients treated with R-CHOP, five developed HBV reactivation, including one patient who died of hepatic failure (P = .0148). Exploratory analysis identified male sex, absence of anti-HBs, and use of rituximab to be predictive of HBV reactivation., Conclusion: Among HBsAg-negative/anti-HBc-positive DLBCL patients treated with R-CHOP, 25% developed HBV reactivation. Close monitoring until at least 6 months after anticancer therapy is required, with an alternative approach of prophylactic antiviral therapy to prevent this potentially fatal condition.