Randomized trial of intrapatient dose escalation of single agent carboplatin as first-line treatment for advanced ovarian cancer: An SGCTG study (SCOTROC 4)

<b>Background:</b> In the absence of toxicity, carboplatin (the most widely used drug in ovarian cancer) is generally given at the same (flat) dose with each treatment cycle. However, retrospective data suggest a correlation between extent of myelosuppression and outcome, as has been observed in other diseases. Our hypothesis was therefore that intrapatient dose escalation, according to nadir blood counts, could lead to an improved outcome compared to conventional flat dosing. <b>Methods:</b> Patients with previously untreated stage IC to IV ovarian cancer were randomized to receive 6 cycles of carboplatin AUC 6 q3 w either with no dose modification except for toxicity (Arm A) or with dose escalations in cycles 2-6 based on nadir FBC (Arm B). The primary outcome measure was progression-free survival (PFS), and a target accrual of 1300 pts was envisaged, aimed at detecting a 20% increase in PFS with 80% power (5% 2-sided level of statistical significance). Results: From March 2004 to November 2008, 937 pts were recruited from 70 centres. Dose escalation occurred in 82% pts on Arm B. The median AUCs actually received were 6.0 (Arm A) and 6.84 (Arm B). As expected, more myelosuppression was seen in Arm B (p < 0.001 for all parameters). More grade 3/4 non-haematological toxicity was also seen in Arm B (31%, vs 22% in Arm A, p < 0.001) but there was no significant difference in global quality of life. To date, 477 PFS events have been observed out of a planned total of 950. The median PFS was 13.9m in Arm A, and 13.5m in Arm B, and the observed hazard ratio (Arm B/Arm A) is 1.04, with 95% C.I. of 0.87 to 1.24. This excludes the clinically relevant benefit of 0.83 used to design the study. A futility analysis also indicated that the probability of a statistically significant result in favour of Arm B at the planned study end was 0.12 at best. <b>Conclusions:</b> Following the Data Monitoring Committee recommendation, the trial has therefore been closed to recruitment, with no evidence of benefit for intra-patient dose escalation of carboplatin. A separate analysis of tissue samples, aimed at elucidating mechanisms of (single agent) carboplatin resistance is ongoing

The clinical role of VeriStrat testing in patients with advanced non-small cell lung cancer considered unfit for first-line platinum-based chemotherapy

Purpose We previously demonstrated that the median survival of patients with poor prognosis non–small cell lung cancer (NSCLC) considered unfit for first-line platinum chemotherapy was <4 months. We evaluated whether VeriStrat could be used as a prognostic or predictive biomarker in this population. Experimental design We conducted a randomised double-blind trial among patients with untreated advanced NSCLC considered unfit for platinum chemotherapy because of poor performance status (PS) or multiple comorbidities. All patients received active supportive care (ASC) and were treated with either oral erlotinib or placebo daily. Five hundred twenty-seven patients had plasma samples for VeriStrat classification: good (VeriStrat Good [VSG]) or poor (VeriStrat Poor [VSP]). Main end-point was overall survival. Results Fifty-five percent patients had VSG, and 83% had Eastern Cooperative Oncology Group (ECOG) 2–3 at baseline. VeriStrat was strongly associated with survival. Among patients managed with ASC only, the adjusted hazard ratio (HR) was 0.54 (p < 0.001) for VSG versus VSP. The association was consistent across patient factors: HR = 0.25 (p = 0.004) and HR = 0.56 (p < 0.001) for ECOG 0–1 and 2–3, respectively, HR = 0.49 (0070 < 0.001) for age≥75 years and HR = 0.59 (p = 0.007) for stage IV. Several ECOG 2–3 patients had long survival: 2-year survival was 8% for VSG patients who had ASC, compared with 0% for VSP. VeriStrat status did not predict benefit from erlotinib treatment because the HRs for erlotinib versus placebo were similar between VSG and VSP patients. Conclusions VeriStrat was not a predictive marker for survival when considering first-line erlotinib for patients with NSCLC who had poor PS and were not recommended for platinum doublet therapies. However, VeriStrat was an independent prognostic marker of survival. It represents an objective measurement that could be considered alongside other patient factors to provide a more refined assessment of prognosis for this particular patient group. VSG patients could be selected for treatment trials because of better survival, while VSP patients can continue to be treated conservatively or offered trials of less toxic agents

Art Psychotherapy and the use of Psychiatric Diagnosis - Assessment for Art Psychotherapy

his article raises concerns over the use of psychiatric language by art psychotherapists in their assessment of patients. Using the situation of assessment for art psychotherapy, it argues for an individual approach to each new patient as free as possible from preconceptions arising from diagnostic labelling. The limitations imposed on the art psychotherapist by such labelling, blocking the recognition and addressing of any individual personal or sociopolitical context, are contrasted with the possibilities of a more open therapeutic interaction available through the avoidance of diagnostic labelling