Thirteen patients with metastatic non-seminomatous germ cell tumours and enlarging metastases consisting of teratoma differentiated only were identified. Patients were managed with surgical resection soon after the growing lesions were documented. Surgical morbidity was minimal and 12 patients are alive (10 are disease-free) at a median follow-up of 28 months.

Purpose: Two germline Fc-g receptor (FCGR) polymorphisms, rs1801274 [FCGR2A;His(H)131Arg(R)] and rs396991 [FCGR3A; Phe(F)158Val(V)] produce altered proteins through amino acid substitutions; both are reported to be associated with cetuximabrelated outcomes. We performed a validation of these polymorphisms in NCIC CTG CO.17, a randomized trial of cetuximab monotherapy in refractory, metastatic colorectal cancer expressing EGFR.Experimental Design: DNA extracted from formalin-fixed paraffin-embedded tissue was genotyped. In addition to log-rank tests, Cox proportional hazard models assessed their relationships with overall (OS) and progression-free survival (PFS), adjusting for clinically important prognostic factors, along with a polymorphism-treatment arm interaction term.

1 A prospective randomised trial was conducted to compare aminoglycoside dose prediction based on individually measured pharmacokinetic data, with dosage based on physician intuition. 2 After 2 days of therapy more patients in the pharmacokinetic group had achieved both peak (6-10 mg l-l) and trough (1-2 mg l-1) target plasma concentrations (P = 0.007), peaks alone (P = 0.01) and troughs alone (P = 0.01). Their mean (s.e. mean) peak concentration was 6.49 ± 0.39 mg 1-1 compared with 4.27 ± 0.52 mg 1-1 in the control group (P = 0.001), with trough concentrations of 1.44 ± 0.22 mg F-1 and 0.94 ± 0.21 mg F' respectively (P = 0.054). 3 After 5 days of therapy, peak and trough concentrations were still significantly higher in the pharmacokinetic group despite empirical dose adjustment (P = 0.01 and P = 0.013 respectively). 4 The mean (s.e. mean) daily dose of aminoglycoside was higher in the computer group (312 ± 17 mg vs 203 ± 13 mg, P = 0.001). 5 These findings suggest that dose estimation based on measured pharmacokinetic parameters is superior at achieving target plasma drug concentrations.

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3538 Background: Addition of (ziv)-aflibercept (A) to FOLFIRI in second-line therapy for metastatic colorectal cancer (CRC) has been shown to be beneficial in phase III VELOUR trial (NCT00561470). A follow-up study (NCT01754272) was undertaken to acquire tumor samples for biomarker analyses and identify subgroups of patients with differential treatment effects. The primary results assessing efficacy according to well-established CRC subgroups defined by RAS, BRAF status and sidedness are reported here. Methods: Tissue specimens were collected for 666 patients from 1226 ITT pts. Suitable specimens were assayed for somatic mutation using NGS targeting extended RAS and BRAF genes. NGS assays with no missing values were obtained for 482 pts. Affymetrix gene chip technology was used for whole-transcriptome profiling; sidedness was extracted from available pathological reports. Differences between subgroups were assessed by interaction analysis. Results: The treatment effects on overall survival (OS) for the 482 pts is still significant HR=0.80 (CI 0.65-0.99), and similar to the ITT (n=1226) results (HR=0.82, CI 0.71-0.93). Two established ways of defining mutations (traditional KRAS exon 2 and extended RAS using NGS) show a trend for a differential effect across mutation groups.(see table for OS). Interestingly, BRAF mutants (which are all RAS wild type) show a trend for better outcome Same is seen for PFS and RR. Sidedness did not affect efficacy (HR: 0.83 (0.63- 1.1) for left and HR: 0.83 (0.54-1.3) for right. Conclusions: None of the mutations subgroup results shows significant interaction, although the ratios of treatment HR favor RAS wild types. Similar trends were observed in published trials with bevacizumab or ramucirumab. Sanofi supported this ISS. Clinical trial information: NCT01754272. [Table: see text]