Background A randomized Phase II study evaluated the activity of weekly paclitaxel versus its combination with trastuzumab for treatment of patients with advanced breast cancer overexpressing HER-2. Patients and methods Among 124 patients randomized, 123 are assessable for toxicity and 118 for response. Patients received weekly paclitaxel single agent (80 mg/m 2 ) or combined with trastuzumab (4 mg/kg loading dose, then weekly 2 mg/kg). HER-2 overexpression was determined by immunohistochemistry (IHC). Patients with 2+/3+ IHC scores were eligible. IHC was compared with HER-2 serum extracellular domain (ECD). Results Patient characteristics were similar in the two arms. Both treatments were feasible and well tolerated with no grade 4 hematologic toxicity. No patient developed cardiac toxicity. The combined treatment was statistically significant superior for overall response rate (ORR) (75% vs. 56.9%; P = 0.037), particularly in the subset of IHC 3+ patients (84.5% vs. 47.5%; P = 0.00050). A statistically significant better median time to progression was seen in the subgroup with IHC 3+ (369 vs. 272 days; P = 0.030) and visceral disease (301 vs. 183 days; P = 0.0080) treated with combination. Multivariable analysis of predictive factors showed that only IHC score retained statistically significant value for ORR (P = 0.0035). Conclusion Weekly paclitaxel plus trastuzumab is highly active and safe and it is superior to paclitaxel alone in patients with IHC score of 3+.

The PGV regimen is associated with a substantial survival gain (MST > 3 months longer) when compared with the PV combination. Because this difference in survival met one of the early stopping rules, the accrual in the PV arm has been stopped (null hypothesis rejected). Enrollment still continues in the PGV and PG arm to ascertain whether the PGV regimen can also produce a significantly longer survival than that obtained with the PG regimen.

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The aim of this study was to assess whether a combination of gemcitabine (GEM) with either paclitaxel (PTX) or vinorelbine (VNR) could be more effective than GEM or PTX alone in elderly or unfit advanced non-small-cell lung cancer (NSCLC) patients. A total of 264 NSCLC patients aged 470 years with ECOG performance status (PS)p2, or younger with PS ¼ 2, were randomly treated with: GEM 1200 mg m À2 on days 1, 8 and 15 every 28 days; PTX 100 mg m À2 on days 1, 8 and 15 every 28 days; GEM 1000 mg m À2 plus PTX 80 mg m À2 (GT) on days 1 and 8 every 21 days; GEM 1000 mg m À2 plus VNR 25 mg m À2 (GV) on days 1 and 8 every 21 days. In all arms, an intra-patients dose escalation was applied over the first three courses, provided that no toxicity of WHO grade X2 had previously occurred. At present time, 217 (82%) patients had died. The median (months) and 1-year survival probability were 5.1 and 29% for GEM, 6.4 and 25% for PTX, 9.2 and 44% for GT, and 9.7 and 32% for GV. Multivariate analysis showed that PSp1 (hazard ratio (HR) ¼ 0.67; 95% CI 0.51 -0.90), and doublet treatments (HR ¼ 0.76; 95% CI 0.59 -0.99) were significantly associated with longer survival. Doublets produced no more toxicity than single agents. GT should be considered a reference regimen for elderly NSCLC patients with PSp1.

The standard treatment for advanced hepatocellular carcinoma (HCC) is sorafenib, a multikinase inhibitor of tumor cell proliferation and angiogenesis. Hyperthermia inhibits angiogenesis and promotes apoptosis. Potential synergic antiangiogenic and proapoptotic effects represent the rationale for combining sorafenib with electro-hyperthermia (EHY) in HCC. A total of 21 patients (median age, 64 years; range, 55–73 years) with advanced HCC were enrolled in the current study between February 2009 and September 2010. EHY was achieved by arranging capacitive electrodes with a deep hypothermia radiofrequency field of 13.56 Mhz at 80 W for 60 min, three times per week for six weeks, followed by two weeks without treatment, in combination with sorafenib at a dose of 800 mg every other day. According to the modified Response Evaluation Criteria in Solid Tumors criteria, 50% achieved stable disease, 5% achieved partial response and 45% achieved progressive disease. No complete response was observed. The progression-free survival (PFS) rate at six months was 38%, while the median PFS and overall survival times were 5.2 [95% confidence interval (CI), 4.2–6.2) and 10.4 (95% CI, 10–11) months, respectively. The overall incidence of treatment-related adverse events was 80%, predominantly of grade 1 or 2. Grade 3 toxicity included fatigue, diarrhea, hand-foot skin reaction and hypertension. In the present study, the sorafenib plus EHY combination was feasible and well tolerated, and no major complications were observed. The initial findings indicated that this combination offers a promising option for advanced HCC.