Background Cytotoxic chemotherapy is generally ineffective in patients with hepatocellular carcinoma. We assessed the intravenous perfusion of doxorubicin-loaded nanoparticles in patients with hepatocellular carcinoma in whom previous sorafenib therapy had failed. Methods We did a multicentre, open-label, randomised, controlled phase 3 trial at 70 sites in 11 countries. Patients with hepatocellular carcinoma with one or more previous systemic therapies, including sorafenib, were randomly assigned to receive 30 mg/m² doxorubicin-loaded nanoparticles (30 mg/m² group), 20 mg/m² doxorubicin-loaded nanoparticles (20 mg/m² group), or standard care using a computer-generated randomisation list prepared by the funder and stratified by geographic region. Patients in the experimental groups received perfusion of the drug every 4 weeks and those in the control group received any systemic anticancer therapy (except sorafenib) as per investigator decision. The primary endpoint was overall survival in the intention-to-treat population. Safety was assessed in the population of patients who received at least one dose of their assigned treatment. This trial is registered with ClinicalTrials.gov, number NCT01655693.

The combined use of CFDNA concentration and integrity is a candidate for a universal screening test of cancer. Upon setting suitable boundaries for the test it might be applied to identify cancer patients, particularly among subjects with predisposing factors. Being less expensive, CFDNA concentration could be applied for mass screening and for patients with values overlapping those of normal and benign subjects, the use of the more expensive, yet more specific, integrity test is suggested.

It has been shown that the level of estrogen receptors (ER), and to some extent progesterone receptors (PR), correlate to a high degree to the response to endocrine therapy in advanced breast cancer patients. To evaluate the prognostic value of ER/PR in early breast cancer, 80 patients with stages I and II were studied. They all underwent modified radical mastectomy. Patients with stage I disease (negative LN) received no further treatment, while those with stage II received standard adjuvant chemotherapy. All the patients were followed for 4 years. The ER and PR were measured in each primary tumor by the glycerol density gradient method. Values of 10 fmole/mgm protein or greater were considered positive (+) and less than 10 fmole/mgm were considered negative (-). The results revealed: (1) Fifty-two patients (65%) had ER+, of which 44 (85%) were also PR+; 28 patients had ER-, of which 24 were also PR- (p less than 0.0001). (2) ER/PR correlated with age as 71% of the patients over age 50 had ER+/PR+, compared to 33% of those under age 50 (p less than 0.05). (3) Postmenopausal patients had a higher incidence of ER+/PR+. (4) Primary tumors less than 2 cm in size had higher ER+; 71% in those with stage I and 80% in stage II. (5) Fifty-eight per cent (38) of patients with ductal carcinoma had ER+/PR+, compared to 67% (4) with lobular carcinoma. (6) The disease-free survival of patients with ER+ tumors was significantly longer than those with ER- tumors (p less than 0.005) both in positive and negative LN patients. The same was true for PR+ compared to PR- (p less than 0.005), but only in those with stage II disease. The overall survival rates were similarly significant in favor of ER+ and PR+ patients (p less than 0.025), but only in stage II disease. It seems that the status of steroid hormone receptors has a major prognostic factor second only to the LN status.

Vemurafenib prolongs survival in patients with BRAFV600‐mutated advanced melanoma. In vitro studies show cytochrome P450 (CYP) 3A4 is involved in vemurafenib metabolism, but the effect of strong inducers or inhibitors of CYP3A4 on vemurafenib exposure in vivo is unknown. This phase 1, open‐label, multicenter study evaluated the effect of rifampicin, a CYP3A4 inducer, on the pharmacokinetics of single‐dose vemurafenib in 27 patients with BRAFV600 mutation–positive metastatic malignancy. Patients received a single oral dose of vemurafenib 960 mg on day 1, oral rifampicin 600 mg daily on days 8–16 (period B), and a single oral dose of vemurafenib 960 mg on day 17 and rifampicin 600 mg daily for days 17–23 (period C), with plasma samples obtained up to 168 hours after vemurafenib dosing. The geometric mean ratio (period C/period A) of area under the concentration‐time curve from time zero to last measurable concentration time point and area under the concentration‐time curve from time zero to infinity for vemurafenib (n = 23 for the pharmacokinetic analysis) was 0.61 (90% confidence interval, 0.48–0.78) and 0.60 (90% confidence interval, 0.47–0.76), respectively, indicating rifampicin significantly decreased vemurafenib plasma exposure by approximately 40%. The geometric mean ratio of the maximum concentration for vemurafenib was 1.1; this slight increase is likely owing to one outlier in period C. Adverse events were consistent with those previously seen for rifampicin and for vemurafenib monotherapy. Caution is advised when dosing vemurafenib concurrently with CYP3A4 inducers.

The results of this study indicate that gemcitabine and cisplatin were active and generally well tolerated in pretreated patients with locally advanced or metastatic breast cancer.