A prospective phase II clinical trial identifying the optimal regimen for carboplatin plus standard backbone of anthracycline and taxane-based chemotherapy in triple negative breast cancer.

Addition of platinums to combination chemotherapy for triple negative breast cancer (TNBC) has shown efficacy and is increasingly accepted in the clinic, yet optimal delivery is unknown. A prospective clinical trial with TNBC patients was conducted to determine the optimal chemotherapy regimen to deliver carboplatin with standard dose dense ACT. Tissue microarray was conducted to isolate markers indicative of response to treatment. 90 TNBC patients were enrolled onto our trial. The most successful version placed the carboplatin on the second and final paclitaxel treatment with liberal hematological parameters. Our final regimen had the lowest grade 3 or 4 toxicities, no delays, no dose reductions of carboplatin, and 32% reduction in paclitaxel doses. Stage I (AJCC7) patients did well with carboplatin-based chemotherapy with zero relapse rate. Reduction in protein levels of androgen receptor and PD-L1 were found to be potential indicators of patient relapse. We have optimized a protocol for the addition of carboplatin to standard of care chemotherapy in TNBC patients. Early data indicates reduced protein levels of androgen receptor and PD-L1 as indicators of response to treatment.Trial registration This trial was registered at Canadian Cancer Trials. http://www.canadiancancertrials.ca/.

Survival of patients with pancreatic cancer treated with varied modalities: A single-centre study.

The present retrospective chart review examined the overall survival (OS) of patients with pancreatic ductal adenocarcinoma based on the disease stage in a sample of 296 patients with pancreatic cancer. Secondary outcome measurements included OS in chemotherapy vs. supportive treatment groups among metastatic patients, OS based on response to chemotherapy among metastatic patients, and OS and disease free survival (DFS) in surgically resected disease with vs. without adjuvant therapy. Data were analyzed using Kaplan-Meier and multivariate cox-regression analyses based on a 95% confidence interval (CI) or an α-value of 0.05. OS was significantly different based on the disease stage, with 3.63 (95% CI, 2.84-4.43), 6.57 (95% CI, 4.06-9.08) and 15.57 (95% CI, 11.79-19.35) months in the advanced, locally advanced, and localized disease groups, respectively. OS was higher in metastatic-stage patients who received chemotherapy [6.07 months (95% CI, 4.75-7.39)] compared with those who received supportive therapy alone [2.50 months (95% CI, 2.16-2.84; P<.001)]. Metastatic-stage patients with partial or stable response to chemotherapy had higher OS [10.53 months (95% CI, 6.35-14.72)] in comparison with those with progression [6.33 months (95% CI, 5.79-6.88)] or an undocumented response [3.30 months (95% CI, 1.76-4.84; P<0.001)]. In patients who underwent surgical resection of localized disease, adjuvant therapy increased the adjusted OS and DFS as compared with surgical excision alone (P=0.013; 95% CI, 0.278-0.862). Positive margins reduced OS [hazard ratio (HR) 2.670; 95% CI, 1.467-4.860]. The present single-site study has demonstrated that OS may markedly differ on the basis of the disease status at the time of diagnosis. Metastatic-stage patients with stable or partial response to chemotherapy had an increased OS, as did surgical patients with localized disease who received adjuvant treatment, after adjusting for margin status.

Use and impact of intermittent versus continuous systemic treatment strategies in metastatic colorectal cancer in routine practice.

BACKGROUND: Randomized trials have shown that intermittent treatment may reduce toxicity without compromising survival in patients with metastatic colorectal cancer (mCRC). A population-based study examined patterns of use of chemotherapy-free intervals (CFIs) in routine practice in Ontario and their impact on survival and toxicity. METHODS: Patients treated with first-line intravenous chemotherapy for mCRC in Ontario between 2007 and 2009 were identified from administrative data. A CFI was defined as more than 56 days between 2 chemotherapy doses. A propensity score analysis was used to compare the survival of patients with CFIs and patients without CFIs, stratified by the type of first-line treatment: irinotecan (IRI), irinotecan plus bevacizumab (IRI-B), and oxaliplatin (OX). Toxicity was estimated on the basis of the rate of emergency room visits and hospitalizations. RESULTS: There were 1989 patients who started first-line chemotherapy for mCRC in Ontario between 2007 and 2009, and 489 (25%) had at least 1 CFI. The median time to the first CFI was 155 days (interquartile range, 82-217 days). There was no difference in survival for the propensity score-matched patients with or without CFIs in the IRI (hazard ratio [HR], 0.93; P = .70) and OX groups (HR, 0.73; P = .06). Survival was worse in the CFI group for patients treated with IRI-B (HR, 1.28; P = .03). Toxicity was lower for patients with at least 1 CFI (0.17 vs 0.25 acute visits per person-month of treatment, P = .007), although the magnitude varied with the treatment type. CONCLUSIONS: Intermittent treatment strategies are being used in routine practice for patients with mCRC. The impact on survival and toxicity varies with the type of first-line chemotherapy.

An unexpected case of coumarin poisoning with coumatetralyl.

A healthy man in his 40s presented with a 1-month history of haemoptysis and was unexpectedly found to have an elevated international normalised ratio (INR). He denied any known exposures to anticoagulants. Testing for the possible aetiologies of a high INR revealed coumarin poisoning with coumatetralyl as the cause. The approach to an elevated INR and management and diagnosis of suspected coumarin poisoning is reviewed.